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Introduction


By Mark Scholz, MD

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Introduction


By Mark Scholz, MD

Once the proper Stage of Blue is assigned (Chapter 1), the different treatments appropriate for that Stage can be considered. Overall, there are four broad categories of treatment available for prostate cancer: observation, local treatments, systemic treatments, and combination therapy.

Observation

Observation, commonly known as “active surveillance,” is the process of monitoring the cancer while reserving medical intervention until some aggressive behaviour is detected.

Local Treatments

Strategies that focus treatment on the prostate gland are called “local” treatments. Examples are surgery, radioactive seed implantation, varieties of external beam radiation therapy (IMRT, Proton, SBRT), and cryosurgery.  In addition, “focal” treatment options have been developed in which only a subsection of the gland is treated.

Systemic Treatments

The main danger from prostate cancer is the possibility of cancer spreading outside the prostate. Men with metastases (or potential microscopic metastases) require systemic treatment that circulates through the blood and treats cancer throughout the whole body. Examples of systemic treatments are hormonal therapies, chemotherapy, immunotherapy, and Xofigo.

Combination Therapy

When a local treatment is combined with a systemic treatment, or if multiple systemic treatments are used at the same time, it is called “combination therapy.” When combination therapy is being considered with the goal of improving survival, the survival advantages need to be balanced against the potential for greater side effects.


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Accessing the Medical Chart to Assign a Stage of Blue


By Peter Scholz

Accessing the Medical Chart to Assign a Stage of Blue


By Peter Scholz

Many treatments have irreversible consequences, so it is worth doing it right the first time. It is commonly understood in medical circles that long-term survival is improved by receiving optimal treatment up front. The first treatment is your best shot at eradicating the cancer. The initial step in the selection process is to determine your Stage of Blue.

First, obtain a copy of your medical records. You have every right to obtain and keep your records. Some offices may charge a small fee for providing you with the records. There is no universal format for charts, and some offices keep more complete records than others. It may be necessary to request the information from more than one doctor’s office to compile all the necessary information. You don’t need a complete understanding of everything in the chart. However, there are certain specific items you need to look for:

Prostate Specific Antigen (PSA) Chronology: Construct a chronological history of every PSA measurement that has ever been taken and the date that it was performed. The PSA results can be found your Lab Reports. The testosterone level is also found in this section of the chart.

Clinical Stage: Information about the digital rectal examination (DRE) will be found in the Progress Notes section of the chart. Results indicate whether a nodule can be felt by the doctor’s finger. The type of nodule that is felt is recorded as the “T” stage. The doctor records his impression of the DRE in the Physical Examination section of the Progress Notes section of the chart per the following table:

T1:    No tumor is felt

T2:   Tumor feels confined within the prostate

T2a: Tumor that can be felt but involves 50% or less of one lobe

T2b: Tumor felt involving more than 50% of one lobe but not both lobes

T2c: Tumor felt in both lobes

T3:   Tumor felt that extends through the prostate capsule

T3a: Extracapsular extension is felt

T3b: Tumor felt that invades seminal vesicle(s)

T4:   Tumor felt that invades rectum or bladder

 

Radiology Reports (imaging studies): The radiology reports will be found in the Radiology section of the chart. Look for the Impression section of the report where the doctor who wrote the report summarizes the essential aspects of the scan results.

Biopsy Report:  The biopsy report will be in the Pathology section of the chart. For each of the biopsy cores that contain cancer, you should make note of the Gleason score and the percentage of the core that contains cancer. 

Finding Your Stage of Blue with The Quiz

The above information from your medical chart provides the data required to assign a Stage of Blue. The formula calculates your Stage by summing up the numbers written in response to the questions in the following quiz. 

The five chapters that follow explain the basic components of the Stages of Blue—PSA, Gleason score, prostate scans, and body scans. Although the Stages of Blue can serve you perfectly well without all these background fundamentals, the goal of this book is to introduce basic vocabulary and thought processes that are utilized throughout the prostate cancer world. Becoming familiar with this information will take the level of conversation with your doctor to a higher level.


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 Peter Scholz is the creative director of the Prostate Cancer Research Institute (PCRI). He received his B.A. in english literature from the University of California, Los Angeles. In addition to branding, design, and media production for the organization, his interests at PCRI are in simplifying, curating, and presenting prostate cancer information in ways that are understandable and accessible to patients. 

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The PSA Blood Test


By Stanley Brosman, MD

The PSA Blood Test


By Stanley Brosman, MD

PSA plays a variety of roles, the most familiar being screening to detect prostate cancer at an early stage. PSA also helps to define the Stages of Blue. Another role of PSA is to detect cancer relapse after surgery or radiation. Lastly, rises or declines in PSA after hormone therapy or chemotherapy help determine whether a treatment is working. 

 

Prostate Cancer Screening is Controversial

PSA screening often leads to the detection of small, essentially harmless cancers. However, doctors and patients frequently overreact, rushing into unnecessary radical treatment. Overtreatment of tiny cancers became such a big problem that in 2011 a government-sponsored team of experts, the U.S. Preventative Services Task Force, issued a warning against routine PSA screening. This recommendation was recently modified, acknowledging the possible value of PSA screening in well-informed patients.

 

Scans Measure the Size of the Prostate

Imaging with ultrasound or MRI improves the accuracy of PSA. Many men run high PSA levels from a condition called BPH that is totally unrelated to cancer. BPH is benign enlargement of the prostate gland, a common phenomenon associated with aging. The main issue is that PSA increases as the gland enlarges, but this rise in PSA has nothing to do with cancer.

 

There is a specific method for determining when the PSA is elevated higher than what would be expected for an enlarged prostate. It works by determining the prostate size in cubic centimeters(cc) using imaging (Chapters 4 and 5) and dividing the size by 10. For example, a noncancerous 30cc prostate should have a PSA of around 3.0; for a noncancerous 50cc prostate the PSA should be around 5.0.  A man’s PSA with a 100cc prostate will be approximately 10.  PSA is only abnormal (the official term is a “high PSA density”) when it’s 50 percent higher than would be expected, based on the prostate’s size. For example, a man’s PSA is abnormal if he has a 30cc prostate and his PSA is above 4.5.  An abnormal PSA for a 50cc prostate is above 7.5.  For a 100cc gland, PSA would need to be above 15 to be suspicious.

 

PSA Density

Doctors use a less intuitive way to determine when the PSA is higher than what can be attributed to an enlarged prostate. The net effect, however, is the same. Instead of dividing PSA into the gland volume, they do the opposite.  They divide the gland volume into the PSA. Using this inverted formula, an abnormal PSA relative to a specific-sized prostate is anything above 0.15.  Men above 0.15, using this formula, are said to have a high “PSA Density.”

 

A Suggested PSA Screening Protocol

It’s reasonable to start checking PSA yearly in men over the age of 45. Men with a family history of prostate cancer or men who are African-American should start annual testing at age 40.  Men over age 75 who are in good health should continue screening.

 

Using PSA to Stage Prostate Cancer

Despite the controversies that surround the use of PSA for screening, there are no controversies about using PSA for cancer staging. Men with a higher PSA at the time of diagnosis, above 10 or 20 for example, are more likely to have cancer that has spread outside the gland. The exact methodology for determining a man’s Stage of Blue, using PSA in combination with other factors, is explained in Chapter 1. 

 

PSA to Monitor for Cancer Relapse After Surgery or Radiation

Cancer recurrence is signaled by a rising PSA. Normally after surgery, the PSA should drop to undetectable levels. Even a small rise in PSA is significant. After radiation, the PSA should generally remain under 1.0, though exceptions certainly exist. The rate of PSA doubling is a very important indicator of the recurrent cancer’s aggressiveness. For example, recurrences associated with PSA levels that require over 12 months to double are low-grade. On the other hand, PSA that doubles in less than three months signals aggressive disease.

 

Determining the Response to Hormone Therapy or Chemotherapy

A PSA decline of more than 30 percent within a couple of months of starting chemotherapy provides a strong indication that the treatment is working. However, not every treatment, even when it is effective, makes an impact on PSA. Two new therapies for Royal—Xofigo and Provenge—clearly prolong life but may show little or no impact on PSA.

 

Conclusion

PSA results must be interpreted in the context of each patient’s overall circumstances by an expert with experience in managing prostate cancer. Unexpected PSA results should always be retested. Laboratory errors are possible and variations also occur between labs. 


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Stanley Brosman, MD is board-certified in Urology.  Former Chief of Urology at UCLA/Harbor General Hospital, a Clinical Professor of Surgery/Urology at UCLA,. and Associate Director of Urologic Oncology at John Wayne Cancer Institute. He is past president of the urology section of the California Medical Society and . Past president of the Los Angeles Urologic Society. He is author or coauthor of more than 80 peer-reviewed scientific articles and over 50 book chapters or monographs. He practices urology with a focus on prostate cancer in Santa Monica, California, at the Pacific

 

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Interpreting the Pathology Report and Gleason Score


By Jonathan Epstein

Interpreting the Pathology Report and Gleason Score


By Jonathan Epstein

The two major components of the pathology report from a random 12-core biopsy are the Gleason score, which measures how aggressive the tumor appears, and the quantity of cancer in the 12-core specimen.

 

What Is The “Gleason Grade” Or “Gleason Score”?

The Gleason grading system assigns a “pattern” to the cancer cells, depending upon their appearance under the microscope. The patterns are graded from 1 to 5. The pathologist assigns a higher number when the appearance of the cancer cells deviates more from the visual appearance of normal prostate gland tissue. The first number in the score is the grade that applies to the most common type of cancer seen in the biopsy. The second number in the score is the next most common grade. These two different grades are then added together to yield the Gleason score. In actual practice, the Gleason score only ranges between 6 and 10.  Therefore, a Gleason 6 is the lowest, most favorable grade possible.

 

What Does It Mean to Have a Gleason Score of 7?

A Gleason score of 7 can mean 3+4=7 or 4+3=7, depending on whether grade 3 pattern or grade 4 pattern is predominant. The biggest therapeutic difference between these grades is that more aggressive radiation therapy protocols are often recommended for Gleason scores of 4+3=7 and higher.

 

What Does It Mean to Have Gleason Scores of 8 to 10?

Gleason score 8 cancers are aggressive, and Gleason score 9 to 10 cancers are more so. However, some patients with Gleason scores 9 or 10 can still be cured. The actual outlook for a specific patient also depends on additional factors, such as PSA, clinical stage, and the extent of cancer on biopsy.

 

Can the Biopsy Gleason Score Determine the Grade in the Entire Prostate?

The Gleason score on biopsy usually reflects the cancer’s true grade. However, in about 25 percent of cases the biopsy underestimates the true grade, resulting in under grading. Somewhat less commonly, over-grading occurs. This occurs when the true grade of the tumor is lower than that which is seen in the biopsy.

 

How Can Patients Be Sure the Reported Gleason Grade Is Accurate?

Assigning the correct Gleason score is developed through experience and practice. It is often prudent to submit the biopsy material for a second opinion to a center managing large numbers of patients with prostate cancer, to confirm the accuracy of the initial Gleason score.

 

Concluding Thoughts

A few years ago, there was a news story about a polar bear attacking a man in Canada.  Shockingly, the report said that the bystanders did nothing to help the poor man. However, upon further review it turned out that the reporter had neglected to report that the bear was only a cub, whose reach was lower than the man's knees. When facing a monstrous behemoth like cancer, the most important question to ask is "What kind of cancer am I dealing with?" 


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Jonathan Epstein, MD received his doctorateMD degree from Boston University. He completed Following his residency in anatomic pathology at The Johns Hopkins Hospital in Baltimore, Maryland, and a fellowship in oncologic pathology at Memorial Sloan Kettering Cancer Center in New York., hHe then joined the staff at The Johns Hopkins Hospital and has been there his entire career. At the Johns Hopkins Medical Institutions, he is Professor of Pathology, Urology, and Oncology; the recipient of the Reinhard Chair of Urological Pathology; and Director of Surgical Pathology. He is the past President of the International Society of Urological Pathology. Dr. Epstein has 744 publications in the peer-reviewed literature and has authored 50 book chapters with a H-factor of 118. His most-frequently cited first or last authored publications is ‘‘Pathological and Clinical Findings to Predict Tumor Extent of Non-palpable (stage T1c) Prostate Cancer,’’ published in JAMA, which established the criteria for active surveillance. 

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Prostate MRI and Targeted Biopsy


By Daniel Margolis, MD

Prostate MRI and Targeted Biopsy


By Daniel Margolis, MD

Multiparametric MRI (MP-MRI) provides a three-dimensional image of the prostate, giving important information about the cancer’s location, size, and how “aggressive” it appears. MP-MRI also greatly increases the confidence that higher-grade cancers are not being overlooked in men on active surveillance. MP-MRI is usually performed without an endorectal coil.

 

“Multiparametric” Means Four Scans in One

There are four different imaging components to MP-MRI. The first is called “T2-weighted,” which creates the clearest images and gives the most capsular detail. The second and third parameters are called diffusion-weighted imaging (DWI) and the apparent-diffusion coefficient (ADC). These provide information about the aggressiveness of the tumor. The fourth, called dynamic-contrast enhancement (DCE), maps the blood flow of the tumor.

 

“PI-RADS”

PI-RADS (prostate imaging reporting and data systems) compiles a score composed of all four parameters—T2, DWI/ADC, and DCE—on a 1-to-5 scale. Lesions with a score of 4 or 5 are more likely to represent clinically significant prostate cancer (Gleason 4+3=7 or higher). Once MP-MRI detects a suspicious lesion, a targeted biopsy can be performed.

 

Evaluating Undiagnosed Men with High PSA Levels

There are notable advantages of MP-MRI over the random 12-core biopsy. First, it is less likely to diagnose clinically harmless cancers, sparing patients from unnecessary anxiety. Second, well-performed MP-MRI only misses significant cancer about 10 percent of the time, and these missed cancers tend to be small and unlikely to spread. To put this in perspective, a well-performed 12-core random biopsy misses high-grade cancer 25 percent of the time.

MRI for Active Surveillance

Until recently, men on active surveillance have only been monitored with periodic random 12-core random biopsies and PSA testing. MP-MRI provides three advantages over random biopsy. First, imaging is noninvasive. Second, imaging can find suspicious areas that might have been missed by previous random biopsies. Third, imaging provides a baseline measurement of the cancer’s size that can be used for follow-up monitoring to detect enlargement. As logical as imaging sounds, active surveillance strategies currently performed in most academic centers do not yet routinely use MP-MRI to detect cancer progression. Nevertheless, this concept is gaining traction.

 

The Future of Prostate MRI

The same imaging techniques for identifying prostate cancer for targeted biopsy can also be used to direct treatment. Focal therapy spares much of the surrounding normal prostate tissue from unnecessary damage. Given the increasing reliance on accurate imaging for state-of-the-art care, the importance of finding centers of excellence with skilled and experienced physicians will assume greater and greater importance.


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Daniel Margolis, MD earned his bachelor’s degree from Berkeley and his doctorateMD from USC, followed by an internship in internal medicine at West Los Angeles Veteran's Administration Hospital. He completed his residency in Diagnostic Radiology at UCLA, and a prestigious fellowship funded by the National Cancer Institute at Stanford. When he was in medical school, his former college roommate’s wife was diagnosed with breast cancer while she was pregnant with their third child. She succumbed to her disease within a few years, which had a pronounced effect on him. He chose to pursue a cancer-based fellowship, after which he stayed in private practice in the Bay Area. During that first year, a high school friend of his was diagnosed with pancreatic cancer, which sadly overtook her, too, again leaving behind a grieving widow and young children. Dr. Margolis decided then that being purely a diagnostic radiologist was not making the most use of his training, and took a job at UCLA where he could apply his skills to cancer research, achieving the most success with prostate imaging. He now serves as the Associate Professor of Radiology and Director of Prostate MRI at Weill Cornell in New York

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Color Doppler Ultrasound and Targeted Biopsy


By Duke Bahn, MD

Color Doppler Ultrasound and Targeted Biopsy


By Duke Bahn, MD

In Chapter 4, MP-MRI technology combined with a targeted biopsy was discussed.  This chapter will discuss an alternative type of imaging, called color Doppler ultrasound (CDU). Unfortunately, CDU followed by targeted biopsy is available in only a few centers around the United States. Even so, this chapter will expound the many advantages of CDU for the diagnosis and staging of prostate cancer.

 

Imaging with CDU utilizes two components; grey scale imaging and color Doppler evaluation of vascularity. With CDU, cancerous lesions appear as a dark spot. In addition, cancer can show increased blood vessel density, or “hypervascularity.” High-resolution CDU readily identifies tumors over 5 mm in diameter. Cancers that are visible on CDU are more likely to be clinically significant (Gleason 4+3=7 or above). Hypervascularity tends to indicate tumors with a higher grade. 

 

PSA, Gland Volume, and Diagnosis

Using an arbitrary PSA level as a trigger for doing a 12-core random biopsy casts such a broad net that over diagnosis becomes inevitable. Men’s prostates vary greatly in size—so the amount of PSA they produce varies greatly. Rather than recommending a 12-core random biopsy to every man with a slightly elevated PSA, my policy is to use a relatively low PSA threshold of 2.5 as an initial trigger to recommend a CDU evaluation. However, in men with risk factors such as family history or African-American descent, I use an even more conservative PSA cut point of 2.0 to recommend a CDU. In older men who tend to have larger prostate glands, a threshold of 4.0 is reasonable.

 

The first step should be to measure the size of the prostate with CDU. If a patient’s PSA is higher than expected for the individual’s prostate size, it increases the likelihood that an underlying high-grade prostate cancer may be present (Chapter 2 explains how to calculate a normal PSA level with allowance for the prostate’s size). Men whose PSA levels are in the normal range for their prostate size should not be subjected to invasive diagnostic procedures unless other suspicious findings are uncovered during the performance of the CDU.

 

Questions that Color Doppler Ultrasound Can Answer:

●      Where is the tumor located within the gland?

●      Does the tumor remain confined within the prostate?

●      What is the tumor’s diameter in millimeters? Does the size of the lesion detected by imaging coincide with the length of cancer reported in the targeted needle biopsy as reported by the pathologist?

●      Is tumor size or vascularity on sequential scanning increasing over time for men who are on active surveillance?

 

Final Thoughts on Prostate Imaging

Prostate imaging dramatically reduces the need for random biopsy. If an abnormality is detected by imaging, a targeted biopsy provides information that is of higher quality using far fewer stabs of the needle. Imaging should precede random needle biopsy. When a biopsy is required, it should be targeted rather than random. 


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Duke Bahn, MD is the director of the Prostate Institute of America. Certified by the American Board of Radiology, his special areas of interest are the early detection and staging of prostate cancer using color-Doppler ultrasound with tissue harmonics. He is also a pioneer in using cryotherapy, as both a primary and salvage treatment for prostate cancer. His published data was the impetus for obtaining Medicare approval for cryotherapy as a viable treatment for prostate cancer. Dr. Bahn has held many academic and professional appointments, including clinical professor of urology, Keck School of Medicine, University of Southern California. 

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Body Scans and Other Predictive Factors


By Fabio Almeida, MD

Body Scans and Other Predictive Factors


By Fabio Almeida, MD

While multiparametric MRI and color Doppler ultrasound are excellent tools for monitoring disease inside the prostate, scanning the rest of the body for cancer that may have spread to the lymph nodes or bones is also critical. Body scans are necessary for every Stage of Blue except Sky. Traditionally, doctors have relied on CT scans and bone scans. However, their accuracy is disappointing. Undetected spread is the most common reason for cancer recurrence after the initial treatment.

Positron emission tomography (PET) scans provide three-dimensional images of the whole body. The most recent and exciting discovery is that prostate cancer relies on fat as its energy source. Prostate tumors rapidly absorb fat when it is injected into the bloodstream, and if the fat is made radioactive by the insertion of radioactive carbon (C11), the tumors “light up” on a scanner. Lymph node metastases as small as 5-6 mm can be detected.

After lymph nodes, bone is the second most common site of metastatic spread. Standard bone scans use a radiotracer called Technetium-99, which is unfortunately not very specific. Other changes in the bone, such as arthritis or benign lesions, can be mistaken for cancer metastasis. A PET scan called NaF18 (radioactive sodium fluoride) provides superior specificity and sensitivity when compared with Technetium-99. NaF18 PET imaging used in combination with C11 acetate PET imaging in the same patient offers the most comprehensive method currently available for detecting cancer metastases.

C11 acetate PET scanning for prostate cancer is a giant leap forward over older scanning techniques, but the C11 scan center must be located immediately adjacent to a cyclotron facility and relatively few such centers exist. Therefore, new types of scans are being explored. Preliminary studies with Ga68 PSMA provide excellent images. Another promising new agent is FACBC (Axumin), which detects increased amino acid metabolism in the cancer cells similar to how C11 exploits increased lipid metabolism.  FACBC is now FDA approved and has recently become commercially available.


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Fabio Almeida, MD graduated top of his class and with honors from The Chicago Medical School. He completed a residency and fellowship in Nuclear Medicine at the University of San Francisco, and is certified by the American Board of Nuclear Medicine and the Certification Board of Nuclear Cardiology. He was in academic practice at the University of California, San Francisco, and private practice until 2005. Dr. Almeida is one of the pioneers in the development and implementation of cross modality fusion for cancer imaging (SPECT, PET, CT and MRI) and PET/CT. He also worked for the Centers for Disease Control after 9/11 for several years as a physician and informatics specialist consultant.

Overview of Royal


By Mark Scholz, MD

Overview of Royal


By Mark Scholz, MD

Royal is defined as the presence of metastases located outside the pelvic lymph nodes or the development of resistance to one of the Lupron-like drugs. Royal is the most life threatening of all the Stages and requires aggressive treatment. The goal is to use maximal treatment to achieve a complete cancer remission and reduce the PSA level to less than 0.1. 

There are two pathways to Royal. One begins with PSA screening leading to the initial diagnosis of localized disease followed by local treatment. After a period, a relapse occurs, the Stage of Blue becomes Indigo and hormonal therapy with Lupron is started. Normally, after about 10 years, resistance to Lupron develops and the Stage becomes Royal. Royal can also occur by a different pathway in men who forgo PSA screening. These individuals come to medical attention when they seek an explanation for bone pain. Evaluation with diagnostic scans reveals that the cancer has already metastasized to the bone.

Three subtypes of Royal can be defined: Low, Basic and High. In Low-Royal, Lupron-resistance exists, but the scans are clear of metastatic disease. Basic-Royal occurs when there are five or fewer metastases are detected by a scan, with at least one of the metastasis located outside or beyond the pelvic lymph nodes. High-Royal means that there are over five metastatic sites with at least one of them located outside the pelvic lymph nodes.

When men are receiving ongoing treatment for Royal, continual monitoring is needed to assess the effectiveness of the therapy. In addition to blood testing and querying patients about any changes in pain symptoms, scans of the body and bones should be performed at least every 6 months. The optimal method for interpreting the results of new scan is to compare it with the results of previous scans. This improves the doctor’s ability to determine if the cancer is progressing or regressing. 


Mark Scholz, MD is the executive director of the Prostate Cancer Research Institute. He is also the medical director of Prostate Oncology Specialists Inc. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is co-author of Invasion of the Prostate Snatchers.  He has authored over 20 scientific publications related to the treatment of prostate cancer.

 

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Early Hormonal Resistance: Low-Royal


By Mark Scholz, MD

Early Hormonal Resistance: Low-Royal


By Mark Scholz, MD

Low-Royal occurs when a man who is Indigo develops a rising PSA while taking a Lupron-like drug, and the restaging body and bone scans are clear. Despite the clear scans, Lupron-resistance is a reliable sign that cancer growth rate is accelerating. When Low-Royal is diagnosed, it should be looked upon as an opportunity to adopt an aggressive treatment protocol and deliver multiple treatment punches before the cancer further progresses and becomes more entrenched. 

Every effort should be made to find the cancer’s location because treatment can be focused more effectively and insurance coverage for FDA-approved treatments will be easier to obtain. Modern PET scans (Chapter 6) often detect metastases at a much earlier stage than standard CT scans or bone scans. Many doctors treat Low-Royal with a mild type of testosterone inactivating pharmaceutical (TIP) that is calledCasodex. However, this may be ill advised. Treatment with other FDA-approved, life-prolonging therapies ends up being postponed. Studies show that delaying life-prolonging therapy impairs treatment results over the long term.

Unsuspecting Doctors and Patients

Doctors and patients are often unaware of the danger from postponing effective treatment. Why? A physician’s thinking may be clouded over by the many previous years of successful disease control with Lupron. They assume that the longstanding quiet behavior of the cancer will continue indefinitely into the future. Men with Low-Royal are in a strange pseudo-reality. They feel healthy and their only problem is that the PSA is rising. However, it is like the calm before the storm. The pussycat is morphing into a tiger. Unfortunately, patients and doctors alike often fail to realize that a rising PSA with a low testosterone indicates that the patient is entering very dangerous territory.


Mark Scholz, MD is the executive director of the Prostate Cancer Research Institute. He is also the medical director of Prostate Oncology Specialists Inc. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is co-author of Invasion of the Prostate Snatchers.  He has authored over 20 scientific publications related to the treatment of prostate cancer.

 

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Oligometastatic Prostate Cancer: Basic-Royal


By Jeffrey Turner, MD

Oligometastatic Prostate Cancer: Basic-Royal


By Jeffrey Turner, MD

Rapid improvements in medical technology are forcing us to rethink our traditional approach to early metastatic prostate cancer. The scans are improved; the therapies are more effective and have fewer side effects, and our understanding of how cancer spreads has been greatly enhanced. Modern theory concedes that men with early metastases may have additional undetected microscopic metastases in other areas of the body. Attempts to cure such patients by simply treating the visible metastases will fail, since the untreated microscopic cancers will eventually grow larger, leading to cancer recurrence. Countering this pessimistic view are the results of recent studies showing that aggressive treatment directed at all the visible metastases can lead to durable remissions. Studies show that durable remissions are more common if metastasis-focused treatment is combined with systemic treatment, which is active against the undetected microscopic metastases. 

An aggressive, combination approach using radiation and TIP seems to give the best results. Studies indicate that Taxotere also enhances survival in men with early metastatic disease. Practically speaking, how can all these different treatments be combined? A possible protocol for Basic-Royal is: 1) Start TIP with Lupron and Zytiga and continue it for a total of 12 months, 2) Taxotere is started immediately and given for a total of 4 to 6 treatments each administered 3-weeks apart, 3) Radiation is administered to the known sites of metastatic disease and possibly to the surrounding lymph-node chain starting a month after the last dose of Taxotere. 

Using an aggressive protocol for Basic-Royal is rapidly gaining adherents. However, this approach is new and many physicians are holding back. Perhaps they are unaware of the studies or maybe they are unconvinced, considering the studies are relatively small.


Jeffrey Turner, MD is a board-certified internist and medical oncologist specializing full time in prostate cancer since 2009. Dr. Turner is an active member of the American Society of Clinical Oncology, American Society of Hematology, and American College of Physicians-Internal Medicine. He was a research associate at UCLA in infectious diseases and molecular biology. He then earned his medical degree in Canada at Memorial University of Newfoundland. He completed his internal medicine residency at the University of British Columbia and fellowship in medical oncology at the Medical University of South Carolina.

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Treatments for High-Royal


By Richard Lam, MD

Treatments for High-Royal


By Richard Lam, MD

Metastases originate from the prostate and spread to another part of the body, most commonly the lymph nodes and bones, and less often to the liver or lungs. Early metastases are usually without symptoms. When cancer becomes widespread, a “whole-body” treatment plan with systemic therapy is necessary. The backbone of treatment is hormonal therapy with testosterone inactivating pharmaceuticals (TIP), also known as androgen deprivation therapy or ADT (Chapters 26 and 29). Deprived of testosterone, prostate cancer cells are unable to replicate and eventually die. The most important predictor of how long TIP will remain effective is determined by the degree of PSA decline after starting TIP, the PSA nadir, which is the PSA level when it arrives at its lowest point. A nadir of less than 0.1 is ideal. When the nadir is above 0.1, hormone resistance and progressive disease is likely to develop quickly. 

When selecting therapy, doctors strike a balance between a treatment’s potency and its side effects. If the PSA rises, or new lesions appear on bone or body scans, a change in therapy is necessary. Provenge’s convenience and lack of toxicity make it a logical first step when men become resistant to Lupron. Provenge requires three visits, one every two weeks, at which time leukapheresis, a process sort of like dialysis, is performed to filter out white blood cells (dendritic cells) from the bloodstream. The dendritic cells are then incubated and “trained” to recognize prostate cancer. Three days later, these “primed” dendritic cells are reinfused back into the patient at the doctor’s office. Dendritic cells activate the killer T cells of the immune system to attack the cancer cells directly. In general, side effects are mild, though occasionally patients will have transient fever, fatigue, nausea, headache, and flulike symptoms. 

The FDA’s approval of Provenge came in 2010 after a prospective, randomized trial demonstrated improved survival compared with placebo. Provenge achieved this in men with relatively advanced disease. Their average PSA was over 50. Further studies in earlier-stage disease have shown a larger survival benefit. For example, Provenge improved survival by 13 months in men with a PSA levels under 22.

Immunotherapy with Provenge is a completely new realm of therapeutic technology. Unlike other types of therapy, PSA levels don’t usually decline. Critics claim this is a sign that Provenge is ineffective. Such criticism is ironic, however, considering that the FDA refuses to use PSA changes as an indicator of a drug’s efficacy. Instead, the FDA demands proof of extended survival in prospective, placebo-controlled trials. Two such trials confirm that Provenge prolongs survival. Even so, some may wonder, “How can life be extended without PSA dropping?” One plausible explanation is that immune enhancement impedes the growth of new cancer cells without causing immediate mortality of the existing cells.

Additional hormonal agents can be added or substituted when Lupron becomes ineffective. For a seasoned prostate cancer road warrior like myself, 2011 marked the start of the “Golden Age” of prostate cancer therapeutics, when a new oral medication called abiraterone (Zytiga) was first approved by the FDA. Zytiga works by counteracting the autologous production of testosterone that commonly occur inside cancer cells that have developed Lupron resistance.  

In a landmark trial, Zytiga was compared head-to-head with placebo in TIP-resistant men who had already tried chemotherapy. The study was stopped early because Zytiga was so effective. In addition to extending life, Zytiga decreased PSA and improved quality of life. Subsequently, in a second study, Zytiga was again compared to placebo, but in patients with earlier stage disease. Zytiga’s anticancer benefits were even more substantial. 

Generally, Zytiga is extremely well tolerated. The most common side effects, if any, are high blood pressure, low potassium, leg swelling, and liver inflammation. Therefore, during the first few months of starting treatment regular lab monitoring is required. Another oral medication called prednisone is also used in small doses to maintain normal potassium levels in the blood. Rarely, prednisone can increase blood sugar, so diabetics need monitoring of their glucose. 

In 2012, another landmark event occurred. The FDA approved another highly-effective oral medication called enzalutamide (Xtandi). In a clinical trial evaluating Xtandi after chemotherapy, Xtandi prolonged survival as well as delaying the onset of pain, bone cancer progression and PSA progression. In addition, quality of life was improved. The most common side effects were hot flashes and fatigue. There was also a risk of seizure, though under 1 percent. In 2014, a second clinical trial evaluating Xtandi prior to chemotherapy showed an even greater improvement in survival, and delayed the need for chemotherapy by 17 months, along with other benefits. In this study, there was no increase in the incidence of seizures. 

In making comparisons between Zytiga and Xtandi, there doesn't seem to be a major advantage of one over the other. Each patient should compare the pros and cons. With Zytiga, the requirement for an additional drug (prednisone) to be prescribed is a disadvantage. Zytiga also requires blood monitoring to check for potassium or liver problems, whereas Xtandi does not. On the other hand, Xtandi is associated with a small risk of seizures. It can also cause fatigue more frequently. 

In 2013, the FDA approved a totally new anticancer technology called Xofigo, a type of “smart radiation” that targets bone metastases. Previous attempts to achieve bone targeted radiation were ineffective and toxic. Xofigo uses alpha emitting radiation derived from Radium-223. Alpha radiation is much more effective and causes far fewer side effects than older radionucleotides which utilized beta radiation. When tested in a randomized clinical trial, Xofigo showed a survival advantage when compared with “best clinical care” which consisted of treatment with Casodex, ketoconazole and spot radiation. Xofigo consists of a simple one-minute injection given monthly for a total of six months. Potential side effects are occasional nausea, vomiting, diarrhea or low blood counts. Although Xofigo extends survival, PSA levels often continue to rise. This “disconnect” between PSA and survival can be disconcerting to doctors and patients alike. Experts hypothesize that Xofigo’s survival benefits work by slowing the rate of cancer cell growth rather than causing precipitous cell death. 

After a patient has been treated with Provenge and Xofigo, and if Xtandi and Zytiga stop working, starting treatment with Taxotere or Cabazitaxel (Jevtana) is usually considered next. Taxotere and Jevtana are chemotherapy and have characteristics that are quite similar to each other. Most of the information provided here about Taxotere is also true for Jevtana. 

Taxotere has two basic roles to play. Taxotere (or Jevtana) is usually reserved for men with progressive metastatic disease after the development of Lupron resistance as well as resistance to Xtandi and Zytiga. Now, however, new studies show that Taxotere’s anticancer effects can be enhanced by using it at an earlier stage, before the onset of Lupron resistance. In one important study, four months of Taxotere added to TIP improved survival by 18 months in men with metastatic, hormone-sensitive disease. Jevtana was initially FDA approved by demonstrating a survival advantage in men who had already taken Taxotere. A more recent study comparing Taxotere with Jevtana showed that Jevtana was equally effective but caused fewer side effects.   

Two “bone-targeted” medications, Xgeva and Zometa, strengthen bone and reduce fractures. Xgeva arrests cancer growth in the bone. Neither, however, impacts survival. With these medications, a severe problem called osteonecrosis can occur. Osteonecrosis consists of a breakdown of gum tissue allowing the exposed bone to become susceptible to recurrent infections. The risk of osteonecrosis is increased when treatment is continued at higher doses and for longer periods. Dental extractions also increase the risk. 


Richard Lam, MD is a board-certified internist and oncologist, and has specialized full time in the treatment of prostate cancer since 2001. He is director of clinical research at Prostate Oncology Specialists, Inc. Dr. Lam has written numerous articles based on his research. Dr. Lam received his undergraduate degree in biology, magna cum laude, at UCLA. He then went on to earn his medical degree at UCLA School of Medicine before completing his residency training in the specialty of internal medicine at UCLA Center of Health Sciences. He completed his oncology and hematology fellowship at Harbor-UCLA Medical Center.

 

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Cancer Research: Striving to Live Longer and Better


By Luke Nordquist, MD

Cancer Research: Striving to Live Longer and Better


By Luke Nordquist, MD

Clinical trials, research trials, and studies all refer to the process that investigates the effectiveness of a new drug, type of therapy, or combination of drugs. There are 3 main phases of an investigational treatment along the road to FDA approval. Phase I trials are small, and 100 percent of the patients receive the investigational treatment. The focus of these studies is to determine a safe and effective dose of the treatment. Phase II trials are a little larger and focus on determining a drug’s anticancer effectiveness. Phase III trials are very large. The goal is to confirm the safety and efficacy of the drug in comparison to the current “gold standard” of therapy. A survival benefit—making someone live longer—is the most common requirement for FDA approval.

If a patient is interested in a participating in a clinical trial, I recommend they start with the physician who is most familiar with their case. A second opinion from an expert is a logical next step. In addition, there are valuable websites i.e., www.clinicaltrials.gov that provide listings of available clinical trials. When embarking on a clinical trial, after an initial screening process, patients are assigned to a treatment. Typically, a clinical trial comparing two or more treatments will be randomized by a computer. 

I think it is important for patients to realize that clinical trials should not be reserved only when all other treatments have failed. They should be viewed as an added tool in the bag of treatment options. Medical advances are occurring so quickly that new medicines may only be available in a clinical trial. Additionally, clinical trials may save money by providing access to expensive medications free of charge. Lastly, clinical trials advance medical science. Men who participate in clinical trials are pioneers. We all need to offer thanks to every cancer patient who has taken that major step of joining a clinical trial.


Luke Nordquist MD, FACP is a board certified in internal medicine and medical oncology. He completed his oncology fellowship at Memorial Sloan Kettering Cancer Center and his residency in internal medicine at the University of South Florida/H. Lee Moffitt Cancer Center. He also has a bachelor’s degree in pharmacy from Creighton University. He was selected by the American Society of Clinical Oncology (ASCO) to sit on the Government Relations Committee, representing the interests of cancer physicians and patients on Capitol Hill. This influential committee is made up of 19 oncologists who are current ASCO leaders and several previous ASCO presidents. Expert panel member for the development of National Prostate Cancer Treatment Guidelines. A selected CALGB member designing new research studies for prostate & urologic Cancers across the nation.

 

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Genetic Testing to Guide Therapy


By Mark Scholz, MD

Genetic Testing to Guide Therapy


By Mark Scholz, MD

Uncontrolled cancer cell growth results from misbehaving genes. An intriguing approach to cancer therapy is to specifically identify the mutated genes. After identification, in some cases a treatment to counteract the damaging effects of that gene may have been developed for the treatment of some other type of cancer besides prostate cancer. 

There are still many challenges to overcome in our attempts to use genetically-guided approach. While we now have the ready ability to identify malfunctioning genes by name, we don’t always know the gene’s actual function. Also, in most cases, medicines to counteract the mutations we detect don’t yet exist. Another problem has been problems obtaining cancer tissue for analysis. Until recently, due to the bone-centric nature of prostate cancer metastases, bone biopsy was the only way to obtain access the tumor cells so genetic analysis could be performed. Fortunately, the ability to analyze cancer DNA released into the blood stream from dying cancer cells may now replace the need for bone biopsy. One assay, performed by Guardant Health called Guardant 360 tests for approximately 70 of the most commonly seen mutations seen in various cancers. 

The fact that targeted therapy for specific mutations can be successful was most notably validated by the discovery that Olaparib, an FDA-approved drug for ovarian cancer, may also be beneficial in men with prostate cancer who have a specific mutation in the BRCA gene. It turns out that this BRCA mutation (or other related types of mutation related to DNA repair) occur fairly frequently in men with advanced metastatic prostate cancer. A study testing Olaparib for treatment of prostate cancer patients was published in the New England Journal of Medicine. It showed that Olaparib was very effective in 15 out of 16 men who had this type of mutation in their cancer cells. In men without this specific type of mutation the response rate to Olaparib was less than 10 percent. Hopefully, genetic testing will lead to further such discoveries.


Mark Scholz, MD is the executive director of the Prostate Cancer Research Institute. He is also the medical director of Prostate Oncology Specialists Inc. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is co-author of Invasion of the Prostate Snatchers.  He has authored over 20 scientific publications related to the treatment of prostate cancer.

 

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Pain Management


By Mark Scholz, MD

Pain Management


By Mark Scholz, MD

Pain can occur for a variety of reasons, many of which may be unrelated to cancer. Therefore, the cause of the pain needs to be accurately diagnosed to ensure that optimal treatment is selected. Generally, the situation should be analyzed with a five-step process:  

I. Query the Patient Specifically about Pain.

The way we perceive pain is strongly influenced by our psychological stage of mind. In a Bayer survey of 410 men with advanced prostate cancer, two-thirds were reported to be handling their pain by ignoring it! One would normally think that uncomfortable patients visiting a doctor’s office would spontaneously volunteer to their doctors that something is hurting. According to the Bayer survey, this assumption is often wrong. Unless men are specifically asked about whether they have any “aches” or “discomfort,” they may visit their doctor’s office and never mention that that they are in pain. Denial blocks access to a correct diagnosis and ultimately to finding a solution for the pain.  

II. Develop an Accurate Diagnosis. Is the Pain Cancer-Related?

Cancer pain from prostate cancer is characteristically located in the bone and tends to have the characteristics of being continuous and progressive. Pain in the joints, pain that comes and goes and transient stabbing or shooting pains are not usually from cancer. While cancer can spread to the bones, it is does not spread to the joints. Joint pain comes from many things including the arthritis. Arthritis can simply be due to aging. It can also come from hormone therapy. Bone pain that is suspected to be coming from metastatic cancer should be confirmed by checking a bone scan. A diagnosis of cancer pain is confirmed when the pain that the patient describes is in the same location as reported on the scan.  

III. If the Pain is Coming from Cancer, First Start a New Cancer Treatment. 

The best quality of life and the best survival rate comes by controlling the cancer (and its pain) with effective therapy. A reduction in cancer pain generally occurs soon after starting a new therapy and is a reliable sign that the therapy is working. While waiting for the anticancer medicine to kick in, which may take days to a few weeks, pain medicines are used. 

IV. Utilize a Stepwise Escalation of Pain and Other Supportive Medications.

Milder analgesics are usually initiated first. Nonnarcotic medications such as Aleve, Motrin, Advil, Tylenol and Celebrex are effective and often underutilized. Generally, with pain medications, treatment will be much more effective if the pain is kept suppressed with continues usage of the medication. Controlling recurring pain after the medication wears off is more difficult and will require a higher dose of medication than if the pain had been kept under control by staying on a regular schedule. All the pain medications are different and have different durations of action. Talk with your doctor about what side effects might occur.  Also discuss how long the medication you are taking is expected to last in your system so you will know how often you need to do repeat dosing. 

If the milder analgesics are ineffective, escalating doses of a short-acting narcotic are usually the next step. Once adequate pain control is achieved, a long-acting narcotic that only requires once or twice a day dosing can be substituted. When there is an urgent need for pain relief, cortisone medications in combination with the nonnarcotic and narcotic medications are helpful. Anti-anxiety medications or antidepressants can also be beneficial.  

V. Consider Radiation and Nerve Blocks.  

If the pain is in one area, a beam of radiation can be very effective. If there are multiple painful areas, injected radiation, called Xofigo, is another option to consider. Neuroleptic pain, due to a tumor pushing or pinching a nerve, may be controllable with a nerve block. 

With good communication and proper medical management, pain can almost always be effectively controlled. Proper management relies on a diagnostic and therapeutic sequence that accurately determines the source of the pain and utilizes medications in a stepwise and escalating fashion. If these basic measures listed here are unsuccessful, consultation with a pain specialist is the logical next step.


Mark Scholz, MD is the executive director of the Prostate Cancer Research Institute. He is also the medical director of Prostate Oncology Specialists Inc. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is co-author of Invasion of the Prostate Snatchers.  He has authored over 20 scientific publications related to the treatment of prostate cancer.

 

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Health Issues for Men with Prostate Cancer


By Jeffrey Turner, MD

Health Issues for Men with Prostate Cancer


By Jeffrey Turner, MD

The surveillance policy, after surgery or radiation, is to check PSA quarterly for the first two years, biannually for the next three, and annually thereafter. For radiation patients, a yearly digital rectal examination is also recommended. After treatment with TIP, some men will be left with chronically suppressed testosterone. Several studies suggest that properly-supervised administration of testosterone is safe. In addition to the need for post treatment surveillance, these ongoing doctor visits offer an good opportunity to screen men for issues unrelated to prostate cancer by important for their overall general good health.  

Every man age 40 and above should have an annual physical, including a skin exam, an eye exam and blood tests.  Annual flu vaccines are advisable. Prevnar-13 and Pneumovax are once-in-a-lifetime vaccines recommended for patients over 65 to reduce the risk of pneumonia. The Zostavax vaccine is recommended to prevent shingles in men who have previously had chickenpox. Men over 50 should strongly consider obtaining a CT scan to check for plaque on the coronary arteries. If there is significant plaque, aspirin, cholesterol pills and an annual stress test needs to be discussed. Men who smoke, or who have quit smoking in the last 15 years, should have annual CT of the chest. Lung cancer can only be cured if it is detected early. Men over age of 50 (or earlier with a family history) can dramatically reduce their risk of dying from colon cancer by doing a colonoscopy or a Cologuard stool test. Lastly, men over age 70, or men who have undergone previous treatment with testosterone inactivating pharmaceuticals are at risk for osteoporosis. Osteoporosis can only be detected by doing a bone density scan.  

Many problems (including prostate cancer) don’t cause symptoms until the condition becomes advanced. Waiting until “something hurts” is the old-fashioned way to do medical care. Modern technology is changing the game. Live longer by diagnosing problems early, before they create symptoms and get out of control.


Jeffrey Turner, MD is a board-certified internist and medical oncologist specializing full time in prostate cancer since 2009. Dr. Turner is an active member of the American Society of Clinical Oncology, American Society of Hematology, and American College of Physicians-Internal Medicine. He was a research associate at UCLA in infectious diseases and molecular biology. He then earned his medical degree in Canada at Memorial University of Newfoundland. He completed his internal medicine residency at the University of British Columbia and fellowship in medical oncology at the Medical University of South Carolina.

 

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Whole Nutrition for Prostate Health & Recovery


By Verne Varona

Whole Nutrition for Prostate Health & Recovery


By Verne Varona

Ideally, the bulk of human food intake should be from whole food sources (unprocessed, unadulterated, natural), with only a small percentage of food products (processed, refined, boxed, bottled, canned, packaged, and powdered). Whole foods provide your body with essential nutrients and avoid harmful additives.

There are two kinds of sugar: complex and simple. Complex sugar comes from whole grains, beans, vegetables, and fruit, and gives enduring energy. Conversely, simple sugar offers quick, fleeting energy. Blood sugar highs and lows create hormonal and chemical stress that predisposes to inflammation, mood swings, compromised immunity, strong sugar or salt cravings, and fatigue. 

The modern diet is high in animal protein, fats, and chemicalized food. Excesses of these foods also leads to inflammation, which plays a role in atherosclerosis. Excessive saturated fats and trans-fats also stimulate atherosclerosis. Of particular concern are processed meats, which are typically manufactured with sodium nitrite, a carcinogen.

Our body is designed to consume a predominantly plant-based, whole foods diet occasionally enhanced with small quantities of animal protein. Contrary to what most people believe, an adult’s daily protein requirement is not very high. By consuming a variety of quality vegetable proteins, one can easily meet their daily requirements.

Before you radically leap into a global diet change, you can make incremental healthy choices by exchanging some of your customary foods for healthier options. Making healthier choices should be based on education, common sense, and self-experimentation. When you take control and do the work, you will benefit.


Verne Varona has become an international renowned keynote speaker with a captivating style that uses humor, insight and practical science to improve and enrich the lives of many. He studied traditional Chinese medicine and nutrition at the East West Foundation of Boston, Massachusetts. With a physician associate, Verne co-created, The ODDS Program (Off Dangerous Drugs Safely); a dietary program designed to reverse pharmaceutical drug dependency. He is the author of, Nature's Cancer-Fighting Foods. Verne's second book, Macrobiotics for Dummies, belongs to the internationally popular Dummies series and is a comprehensive work that embraces a flexible, multi-cultural health perspective on body, mind, and spirit. 

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Fitness and Longevity


By Mark Scholz, MD

Fitness and Longevity


By Mark Scholz, MD

The risk of a sedentary lifestyle is about the same as a pack-a-day smoking habit. “Sitting is the new smoking.” After age 60, just through the normal aging process, men lose 1% of their muscle every year. Hormonal treatments accelerate muscle loss. Strength training to build muscle mass, therefore, promotes optimal health. 

A reasonable program that alternates two programs every other day is outlined below. You can start without any weights whatsoever. Slowly add weight as you gain strength.  

PUSH DAY        Do 3 sets of 12 repetitions

  • Pectorals | Raise your arms up in front of you while lying on your back. Lower your arms back down until almost touching the ground. 
  • Pectorals | Stand arm’s length from a wall and place your hands flat on the wall at chest level. Bend your arms slowly with straight back. Straighten out and return your body to the starting position.
  • Triceps | Extend a weight behind you while leaning forward while sitting on a chair.
  • Shoulders | Extend your arms straight out on each side until they are parallel to the floor. Then start to make circles with each outstretched arm. 
  • Deltoid | Extend your arms straight out to each side while standing until your hands are level with your shoulders. Lower both arms back to your side. 
  • Abdomen | Torso twists (Do 3 sets of 25 repetitions.) 

PULL DAY        Do 3 sets of 12 repetitions 

  • Biceps | Curl the weight up in front of you while standing. 
  • Back muscles | Sitting, pull your shoulder blades together; hold for 5-7 seconds. 
  • Back muscles | While leaning forward with one hand supported by a chair or table, dangle a weight in the free arm and pull it straight up toward your chest. Then straighten your arm until it again is fully extended.
  • Legs | Stand normally. Use something next to you for balance if necessary.  Bend both legs, squatting down about halfway to the floor, then straighten up. Keep your knees behind your toes.
  • Calves | Start flat-footed with your feet shoulder width apart. Push up so you are standing on your toes, then release. 
  • Abdomen | Sit ups (Do 3 sets of 25 repetitions.)

Mark Scholz, MD is the executive director of the Prostate Cancer Research Institute. He is also the medical director of Prostate Oncology Specialists Inc. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is co-author of Invasion of the Prostate Snatchers.  He has authored over 20 scientific publications related to the treatment of prostate cancer.

 

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Supplements for Men with Prostate Cancer


By Mark Moyad, MD

Supplements for Men with Prostate Cancer


By Mark Moyad, MD

When it comes to dietary supplements, less is more. Mega-doses suggest a worse outcome or prognosis in patients with cancer. 

Vitamins

B12 may be needed if blood tests show a deficiency. Excess B vitamins may promote heart disease and cancer growth. Researchers have not found that Vitamin C helps prevent or treat prostate cancer. For Vitamin D, I generally recommend 1,000 IU daily if the level is below normal. Men with prostate cancer should not take an individual Vitamin E supplement. Higher doses of Multivitamin pills may feed prostate tumors. Taking a children’s multivitamin several times a week, not to exceed one pill a day, makes more sense. Folic acid and Zinc in higher amounts have been associated with a higher risk of aggressive prostate cancer in human studies. 

Fish Oil (Omega-3 fatty acids)

Pills containing EPA and DHA may reduce the risk of cardiovascular events and may have anti-arthritic and anti-depressive properties. Some new research suggests it could encourage the growth of some prostate cancers. 

Ginger

500-1,000 mg per day may reduce nausea during and after chemotherapy.  

Korean Red Ginseng, MACA, L-arginine, L-citrulline and American Ginseng

Preliminary data shows they improve sexual health. Panax ginseng may help reduce fatigue in cancer patients. American ginseng from the Ginseng Board of Wisconsin is arguably the safest, least expensive, and most effective option for fatigue.   

Glucosamine, Pycnogenol, SAM-e, Lycopene and Resveratrol

Show no evidence of anti-prostate cancer activity. The few studies published to date are inconclusive and controversial. 

Quercetin

It has been used with some success in chronic nonbacterial prostatitis.

Saw Palmetto & Other BPH Supplements

In two major clinical trials, the most commonly used dosage was safe but did not work better than a placebo.

Selenium

Supplements may increase the risk of aggressive prostate cancer!

Tea and Tea Supplements

Most forms of tea, including black, green, herbal, and oolong are healthy and have few or no calories, so enjoy drinking them. However, please keep in mind that tea-based dietary supplements or pills (not the drink) have no solid proof from human studies that they do anything against prostate cancer. A large clinical trial of high-dose green tea supplements in patients with advanced cancer showed no real benefit. 

Whey Protein or Protein Powder

This can be taken as a powdered drink supplement (never as a pill) for any man needing more high-quality protein for health, weight loss and to support muscle health.

Zinc

Zinc supplements in high dosages, 80 to 100 mg per day or more, should be avoided. Recent human research has linked higher doses of zinc from dietary supplements to abnormal immune changes, a potential reduction in the impact of bone-building drugs, abnormal changes in cholesterol blood tests, increased risk of urinary tract infections, kidney stones, prostate enlargement, and an increased risk of aggressive prostate cancer. 

Marijuana Cures Everything, Dude?!  

So, let’s review: Personally, if you are healthy, I think the risks of marijuana outweigh the benefits, unless of course you win the lottery and just want to try it one time to celebrate the fact that you never again have to listen to your boss or some of your annoying coworkers. Marijuana has NOT been proven to be heart-healthy and in fact it could be heart-unhealthy. And the smoke does not make the lung tissue happy, even though you could feel temporarily happy. 

I frequently hear, “Marijuana is natural.” So, should I get excited about it? Just because it is natural is not the reason I get excited about diddly squat (aka anything). I mean, poison ivy and arsenic are natural, folks, but I usually do not recommend those things—except to my big brother when he pushed my face in the snow when we were kids…  

Do I think it’s possible that marijuana or one of its compounds can fight cancer or encourage the growth of cancer? Yes! But at this point, we have no conclusive evidence one way or the other. It’s dangerous to treat humans unless studies in humans show that it works. In Europe, a laboratory study showed that a certain drug could impact a cannabinoid receptor in the brain. “Experts” were convinced that it would be a great weight-loss drug and it was marketed briefly under the trade name of Acomplia (Google that bad boy). It was removed from the market because of serious side effects such as anxiety, suicidal ideation, nausea, and, in some cases, the development of multiple sclerosis. 

Final Thoughts

Always talk to your doctor about any pill or supplement. Use the same approach to taking a dietary supplement as you would use for starting a prescription medication.


Mark A. Moyad, MD, MPH is arguably one of the world’s leading medical experts on diet and dietary supplements. He is the Jenkins/Pokempner Director of Preventative and Alternative Medicine at the University of Michigan Medical Center-Department of Urology.  He graduated from the University of South Florida College of Public Health and the Wayne State University School of Medicine.  He is the primary author of over 150 published medical journal articles, the past editor-in-chief of the medical journal Seminars in Preventive & Alternative Medicine (Elsevier Publishing), and has given over 5,000 lectures around the world to the public and health care professionals in virtually every medical specialty and major medical center.  He isco-author or author of 14 academic and consumer books including The Supplement Handbook: A Trusted Expert’s Guide to What Works & What’s Worthless for more than 100 conditions.  He has been a consultant and/or interviewed for most major magazines, websites, radio and television shows devoted to health in the U.S., and appears regularly on a variety of network news/programs.

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The Key: Knowing Your Stage of Blue


By Mark Scholz, MD

The Key: Knowing Your Stage of Blue


By Mark Scholz, MD

The best protection against receiving the wrong type of treatment is good knowledge of how your particular type of prostate cancer is likely to behave. It is especially important to understand which Stage and which subtype of prostate cancer you are facing. Accurate information improves self-confidence, preparing you for a discussion with your doctor about which treatment option is best for you. 

Knowing your Stage of Blue protects you from being assigned to the wrong treatment. As this book has clearly shown, each of the Five Stages are treated very differently. Men with more life-threatening disease need more intense treatment (and should be willing to put up with greater side effects). Men with harmless types of disease need no treatment at all. To put this into context, let’s summarize the impact of the Stages of Blue on longevity:

 

Sky—Even with no immediate treatment, shortened longevity is not a risk.

Teal—Even with relatively mild treatment, shortened longevity is a very small risk.

Azure—Even with combination treatment, shortened longevity is a possibility.

Indigo—Even with combination therapy, there is a substantial risk of shortened longevity.

Royal—Even with maximal therapy, shortened longevity occurs in over half of the men.    

 

The greatest danger for Sky and Teal is overtreatment. With the other Stages of Blue, their risk is increased by delaying treatment. Knowing their prognosis enables men to learn whether their treatment goals should be characterized by reticence and procrastination versus aggression and urgency. 

We have presented the Five Stages of Blue, each with 3 subtypes. Hopefully this approach is helpful. The PCRI exists to help your endeavors for an optimal outcome. Please visit our website at pcri.org or call our Helpline at (800) 641-7274 for further assistance.

Appendix I. Table of Five Stages of Blue

Rx. = Treatment; MP-MRI = Multiparametric MRI; CDU = Color Doppler Ultrasound; CT = CAT scan; ECE = Extracapsular Extension; SVI = Seminal Vesicle Invasion; N1 = Pelvic Lymph Node Mets; “Small” = < 12 mm; PSADT = PSA Doubling Time; PET = C11 Axumin or PSMA; XRT = Radiation; Testo = Testosterone; BS = Bone Scan

Appendix II.  Summary of the Five Stages of Blue

Sky (Low-Risk) is a relatively harmless condition. The biggest risk for Sky is overtreatment. Within Sky, the most favorable subtype of all (Low-Sky) is defined by all the usual Sky criteria of Gleason 3+3=6, PSA less than 10, and minimal or no palpable disease on DRE.  In addition, to qualify as Low-Sky, the PSA density must be less than 0.15 (Chapter 2), there can be no more than two biopsy cores containing cancer and no single core can be more than 50 percent involved. Men in Low-Sky have the best chance for staying on surveillance long term without requiring treatment. At the other end of the spectrum (within Sky) is High-Sky which is defined by all the usual Sky criteria but with one or more of the following: palpable disease, a PSA density over 0.15 or more than 50% of the biopsy cores containing cancer. These men are at somewhat greater risk for disease progression, the eventual need to go off active surveillance and undergo some form of treatment. Basic-Sky falls between the Low and High subtypes. As would be expected, the risk for men with Basic-Sky to require future treatment is intermediate between Low and High

Teal (Intermediate-Risk) is a generally low-grade condition associated with excellent long-term survival, although, unlike Sky, most men undergo treatment. In addition to all the usual Teal criteria of Gleason 7, PSA from 10-20 or palpable T2b disease (Chapter 1), men with Low-Teal are only allowed to have one of these elements. In addition, the Gleason must be 3+4=7 not 4+3=7, the amount of grade 4 must be less than 20 percent and no more than two biopsy cores can contain cancer. Many men with Low-Teal can be managed like Sky, that is, with active surveillance. The criteria for Basic Teal, also known as favorable Intermediate-Risk prostate cancer is like Low-Teal except for having a higher number of biopsy cores with cancer, between 3 and 6.  High-Teal, also known as unfavorable Intermediate-Risk prostate cancer is defined by having two or more of the usual Teal criteria or more than 6 biopsy cores that contain cancer. Chapter 19 discusses the different treatment approaches one should consider for Basic and High Teal.

Azure (High-Risk) also contains three subtypes.  Low-Azure is Gleason 4+4=8 with all other criteria being favorable—two or less positive biopsy cores, no biopsy core more than 50% involved with cancer, a PSA less than 10, and minimal or no palpable disease (T1c or T2a). Men with Low-Azure can consider having treatment along the lines of what is used for High-Teal (Chapter 19). High-Azure is defined by having at least one of the following: A PSA over 40, Gleason 9 or 10, more than 50 percent positive biopsy cores, or cancer that spreads overtly outside the prostate. Basic-Azure falls between the Low and High subtypes. Basic-Azure is managed aggressively with an extended duration of hormonal therapy, seeds, and IMRT, as is High-Azure. Though with High-Azure, additional therapy with Zytiga, Taxotere or both should be considered.   

Indigo (Relapsed Disease) occurs when surgery, radiation, or some form of focal therapy fail to cure the disease. Men who are Low-Indigo are judged to be at very low risk for harboring any lymph node metastases. To qualify as Low-Indigo, the PSA must be under 0.5 after previous surgery, less than 5.0 after previous radiation or focal therapy and the PSA doubling time must be over 8 months. In addition, the original Stage of Blue prior to initial therapy with surgery, radiation, or focal therapy must be Sky, Low-, or Basic-Teal. 

Men with High-Indigo have metastases proven either by surgery or with scans that show unequivocal pelvic node involvement. Scans and surgical pelvic lymph node staging in men with Basic-Indigo show no overt lymph node metastases. However, various factors suggest a significant likelihood that microscopic pelvic lymph node disease is present. Such factors include higher PSA levels, a fast PSA doubling time, or an original Stage of Blue higher than Basic-Teal. Appendix I provides the specific thresholds. The intensity of treatment selected for Low-Indigo may be relatively mild since less aggressive therapy may be curative and further options can subsequently be implemented if necessary. Aggressive combination therapy is often used for Basic- and High-Indigo for two reasons: To enhance longevity and to reduce the likelihood of needing additional hormonal therapy down the line. Avoiding hormonal therapy substantially improves quality of life. 

Royal (Hormone-Resistance or Metastases Outside the Pelvic Nodes) is what defines Royal. Low-Royal is “pure” hormone resistance without any proven metastases. Hormonal resistance is defined as a rising PSA with a testosterone level less than 50. Basic- or High-Royal means that metastases outside of the pelvic nodes are proven to exist. With Basic-Royal the total number of metastases is five or less. Men with High-Royal have more than five metastases. Clearly, the likelihood of detecting metastases is influenced by using the best available type of scan. For example, better scans using PET technology (Chapter 6) may “convert” men who were thought to be “Low-Royal” into Basic- or High-Royal. 

Treatment recommendations for Royal can vary widely because doctors are struggling to digest the explosion of new knowledge. Better treatments, improved scans, and a deeper understanding of staging, genetics, and immunotherapy have all conspired to complicate and increase the controversy about how to select optimal therapy. Overall, however, we can certainly be thankful for the many new breakthroughs and the many additional discoveries that are expected soon.


Mark Scholz, MD is the executive director of the Prostate Cancer Research Institute. He is also the medical director of Prostate Oncology Specialists Inc. He received his medical degree from Creighton University in Omaha, NE. Dr. Scholz completed his Internal Medicine internship and Medical Oncology fellowship at University of Southern California Medical Center. He is co-author of Invasion of the Prostate Snatchers.  He has authored over 20 scientific publications related to the treatment of prostate cancer.