water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg
water-blue-ocean.jpg

Introduction


By Mark Scholz, MD

SCROLL DOWN

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.


Dr.20Scholz-240x300.jpg
water-blue-ocean.jpg

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 pages 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.


Peter.jpg

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. 

water-blue-ocean.jpg

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. 


476fdca0-0170-45c7-840e-ce45fa8f3d3fzoom-2.jpg

Stanley Brosman, MD is board-certified in Uurology.  Former Cchief of Uurology at UCLA/Harbor General Hospital, a Cclinical Pprofessor of Ssurgery/Uurology at UCLA,. and Aassociate Ddirector of Uurologic Ooncology at John Wayne Cancer Institute. He is past president of the urology section of the California Medical Society and . Ppast 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

 

water-blue-ocean.jpg

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?" 


Epstein.jpg

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 asand 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 Ppresident 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 Nonpalpable (stage T1c) Prostate Cancer,’’ published in JAMA, which establisheds the criteria for active surveillance. 

water-blue-ocean.jpg

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.


Dan Maargolis MD.jpg

Daniel Margolis, MD earned his Bbachelor’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

water-blue-ocean.jpg

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. 


Duke Bahn MD.jpg

Duke Bahn, MD is the Ddirector 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. 

water-blue-ocean.jpg

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.

This wraps up the introductory section of the book. Armed with the results from your quiz in Chapter 1, which enables you to determine your Stage of Blue, it is now possible for you to jump ahead to the Chapter that addresses your Stage specifically:

 

                                                Sky:                Chapter 7  

                                                Teal:               Chapter 15

                                                Azure:            Chapter 25

                                                Indigo:           Chapter 30

                                                Royal:            Chapter 36


Fabio Almeida MD.jpg

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.

Azure Overview


By Mark Scholz, MD

Azure Overview


By Mark Scholz, MD

The official medical terminology used by doctors for Azure is “High-Risk.” Criteria for a man to be in Azure are: 

  1. No previous treatment with surgery or radiation.
  2. Bone scans without metastasis. 
  3. One or more of the following three risk factors:
    • PSA above 20 and less than 100, or
    • Gleason score above 7, or
    • A clinical stage of the prostate tumor that is felt by digital rectal exam extending across the midline of the gland i.e., stage T2b (Chapter 1).
  4.  Any cancer detected on a scan outside the prostate including the pelvic lymph nodes, but no cancer that has spread further beyond the pelvic lymph nodes.  

Azure is divided into three subcategories—Low, Basic, and High. Low-Azure is when PSA is under 10 and only small amounts of Gleason grade 8 tumor are present in one or two biopsy cores. Men with Low-Azure need to be evaluated with a multiparametric MRI (MP-MRI) to confirm that the tumor is relatively small and without any evidence for extracapsular extension or seminal vesicle invasion. Treatment for Low-Azure is the same as treatment for High-Teal. Men with Low-Azure should review the Teal section of the book (Section III starting with Chapter 15).

High-Azure is indicated by a Gleason score of 9 or 10 and/or a clinical stage of T3 or more (Chapter 1). High-Azure is also signaled by a PSA over 40 or when the cancer invades the seminal vesicles, the bladder, the rectum or the pelvic lymph nodes. Basic-Azure is defined as neither Low nor High (see Appendices I and II for further explanation of subtypes). 

Understanding the Importance of Microscopic Metastasis

If micro metastases are present and untreated, cancer recurrence is almost inevitable. When there is a significant likelihood of microscopic metastases, as is certainly the case with High-Azure, systemic hormonal therapy with testosterone inactivating pharmaceuticals (TIP) improves the chance for cure. One question frequently raised by patients relates to the performance of surgery to remove potentially cancerous pelvic lymph nodes with the goal of improving cure rates. While surgical removal of the pelvic lymph nodes may be useful for detecting microscopic metastases, surgical removal is not an effective method for improving cure rates. Surgeons simply can’t remove all the nodes. Therefore, other types of therapy are much more effective. Treatment protocols for High-Azure that fail to incorporate a strategy for treating potential microscopic metastases are associated with higher rates of cancer recurrence. 

Throughout this section of the book and the next section on Indigo, we will be continually revisiting the question of how to deal with potential microscopic metastases. Specifically, we will discuss all the different treatment modalities—TIP, radiation to pelvic lymph nodes, or chemotherapy—and when to use them. The goal is preemptive eradication of microscopic disease at an early stage, at a point when the disease is more likely to be curable. In the following chapter, we will introduce the varied ways TIP can be utilized, depending on the Stage of Blue and the circumstances of each individual patient.   


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.

 

water-blue-ocean.jpg

Testosterone Inactivating Pharmaceuticals


By Mark Scholz, MD

Testosterone Inactivating Pharmaceuticals


By Mark Scholz, MD

 

Hormonal therapy is a mainstay for Azure, Indigo, and Royal. The testosterone inactivating pharmaceuticals (TIP) fall into three broad categories:

  1. Lupron-like medications work by blocking luteinizing hormone (LH) which comes from the pituitary gland. When LH levels in the blood are reduced, the testicles stop producing testosterone. There are two types of injectable drugs that block LH. The agonists, which are called Lupron, Eligard, Trelstar, and Zoladex.  There is only one drug that works as an antagonist. It is called Firmagon. 
  2. Anti-androgen pills “block” testosterone activity without eliminating it from the blood stream. Anti-androgens are less potent but have fewer side effects, and are occasionally substituted for Lupron-like drugs in frail or elderly men. The trade names of the FDA-approved anti-androgens are Casodex, Flutamide and Nilutamide. Their generic names are bicalutamide, eulexin and nilandron.
  3. Zytiga and Xtandi are FDA-approved medications for men who have become resistant to the “Lupron-like” medications. Zytiga also improves survival in men with High-Azure. Zytiga works in the cancer cell internally by blocking the synthesis of testosterone. Xtandi also works inside the cancer cell. It prevents testosterone from activating the androgen receptor that turns on cell growth. The side effects of Zytiga and Xtandi are similar to that of the Lupron-like drugs, with some exceptions (Chapter 29).  

Both the anticancer efficacy and the treatment-related side effects of TIP are increased by continuing the duration of treatment for a longer period. Therefore, the duration of TIP is adjusted in accordance with each individual’s specific situation. The following list presents eight ways that TIP is commonly used:

  1. Men with High-Teal who are undergoing radiation often begin TIP two months before starting radiation and continue for a total of four to six months of therapy. As noted in the previous chapter, treatment for Low-Azure is similar to High-Teal.
  2. Men with Basic-Azure and High-Azure who are undergoing radiation are typically treated with TIP for 18-24 months. Treatment starts two months before radiation and continues during and after the radiation.
  3. Men with relapsed disease (Indigo) often receive intermittent TIP. This means that an initial course is continued for six to 12 months and then stopped. During the off-period, PSA levels are monitored every three months. A second cycle of TIP is initiated when the PSA rises to a prespecified level, usually between 3 to 6.
  4. With occasional exceptions, men with Royal generally remain on TIP indefinitely.
  5. Men with Royal who become resistant to Lupron are usually administered Xtandi or Zytiga. Treatment with Xtandi or Zytiga is continued until there is clear evidence of new metastases on a bone scan or body scan. A rising PSA by itself, without new metastatic lesions, is an insufficient rationale to stop Xtandi or Zytiga. 
  6. TIP has a potential role aside from its anticancer effects to shrink an enlarged prostate gland prior to a radioactive seed implant. Otherwise, some men with excessively large prostates would be ineligible for seed implantation. 
  7. TIP can be used as a primary therapy instead of surgery or radiation to treat men with Teal (Chapter 22). 
  8. TIP can be used after surgery in men with Azure. This is controversial because older studies evaluating TIP for Teal after surgery showed no improvement in cure rates. However, those studies used only three months of TIP. Subsequent studies in Azure and Indigo using TIP for a longer duration show improved survival. 

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.

 

water-blue-ocean.jpg

The Azure Stage of Prostate Cancer


By Mark Scholz, MD

The Azure Stage of Prostate Cancer


By Mark Scholz, MD

With Azure, the first step is to make sure no detectable metastases exisit outside the pelvic lymph nodes. Since scanning technology is far from perfect, questionable lesions are often detected by a bone scan. These can be further evaluated with an MRI focused specifically on the lesion to determine if the questionable abnormality has a cancerous cause or is due to some other benign process. If the MRI fails to resolve the uncertainty, a CT-directed needle biopsy of the lesion may be necessary. Accurate assessment of the extent of disease and the location of the cancer in the body is essential for arriving at an optimal treatment plan.  

Since cure is a top priority with Azure, let’s consider which type of treatment leads to the best results. Dr. Peter Grimm compiled all the studies that report cure rates for Azure. He found that either seed implants or seed implants plus IMRT, on average, provide higher cure rates compared to IMRT alone or surgery. Recently, a large randomized trial called ASCENDE-RT came to the same conclusion. The cure rate for men treated with IMRT alone was only 63 percent, whereas 83 percent of the men were cured who received IMRT plus a seed implant. The results of the ASCENDE-RT trial confirm that seed implants give the best results for Basic-Azure. 

Why Would Seeds Work Better than Surgery?

With surgery the problem is that the bladder and rectum are only millimeters from the prostate. Incomplete cancer removal (positive margins) is therefore a frequent problem. In a study of 9,300 men undergoing surgery for Azure at Johns Hopkins, 80 percent developed recurrent cancer over the subsequent 15 years. Salvage radiation ended up being necessary to “sterilize” the residual cancer over half the time. To avoid undergoing both surgery and radiation it is better to simply start with radiation and skip the surgery altogether. 

Prophylactic Treatment of the Pelvic Nodes with Radiation

Basic and High-Azure are associated with a substantially greater risk of microscopic cancer (cancer invisible on scans) in the pelvic nodes. Therefore, it is logical to consider giving prophylactic radiation to the pelvic lymph nodes even when the scans appear normal. However, when the risk of cancer spread to the nodes is low, pelvic radiation should be withheld. The risk of microscopic pelvic node metastases can be calculated using the following equation: 

Probability of metastasis Probability of metastasis (in %) = 

GS is the Gleason score and T is the clinical stage estimated by digital rectal examination. T = 0 for stage T1c, 1 for T2a, and 2 for T2b or T2c (see Chapter 1 under the section titled: “Clinical Stage”). Dr. Mack Roach, Chief of Radiation at UCSF, recommends that only men with a risk above 15% should undergo node radiation. 

Testosterone Inactivating Pharmaceuticals (TIP)

After IMRT and seeds, TIP is the third leg of the Azure treatment triad. In the most famous study evaluating the benefit of TIP, the mortality rate from cancer after 10 years in the men treated with TIP was reduced to 10 percent compared to 30 percent in the men who did not receive TIP. There are many additional studies that have arrived at the same conclusion. For Basic-Azure, men should receive a combination of IMRT, seed implants and TIP. IMRT should be administered to the prostate and possibly to the pelvic nodes. Men with High-Azure should receive IMRT to the prostate and lymph nodes along with TIP for 18 months. Adding Zytiga also seems prudent considering the results of recently published trials. 


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.

 

water-blue-ocean.jpg

Unorthodox Therapies for High Azure


By Mark Scholz, MD

Unorthodox Therapies for High Azure


By Mark Scholz, MD

Chemotherapy or Zytiga for High-Azure 

In a large randomized trial called STAMPEDE, men with High-Azure showed a survival improvement when six cycles of Taxotere was added to TIP plus radiation compared to men treated with TIP plus radiation without Taxotere. Two additional studies, presented at the annual meeting of the American Society of Clinical Oncology in 2017, also reported a survival advantage in men with High-Azure treated with Zytiga. Since Zytiga is less toxic than Taxotere, the unanswered question is whether Zytiga should be substituted for Taxotere or given in combination with Taxotere.    

Adding TIP to Surgery in Men with Azure

The average five-year cure rate for Azure using surgery alone as reported in multiple phase II studies is only 42 percent. It is logical to wonder if starting TIP right after the operation would improve cure rates, as it does with radiation. In one study published in the New England Journal of Medicine, the ten-year survival rate was 85 percent in men treated with immediate TIP after surgery, compared to only 60 percent in men whose TIP was delayed to the time of cancer progression. In another study, Tanya Dorff, a medical oncologist from USC, reported in the Journal of Clinical Oncology that the 5-year cure rate was improved to 87 percent if TIP was added right after surgery.  

Additional Options for Azure

Some medications, not normally considered as cancer therapies, have been evaluated for their potential anticancer effects. Credible studies have reported that taking aspirin, statin drugs, and Metformin may prolong survival in men with Azure.


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.

 

water-blue-ocean.jpg

Reducing the Side Effects of TIP


By Mark Scholz, MD

Reducing the Side Effects of TIP


By Mark Scholz, MD

Blocking testosterone, a hormone that induces libido, strength, endurance, emotional stability, and potency, creates all kinds of side effects. This chapter introduces some methods for counteracting these problems. 

Fatigue and Lassitude

Strength training to build muscles should be considered routine (Chapter 45). 

Hot Flashes

Low-dose Effexor or Neurontin, or acupuncture can be helpful. If these are ineffective, one can consider a transdermal estrogen patch such as Vivelle Dot.   

Breast Enlargement

If there is early evidence of breast growth, an estrogen-blocking pill such as Femara should be considered. Alternatively, preventative radiation to the breast area can be administered prior to starting TIP.

Erectile Atrophy

The normal pattern of nocturnal erections can often be reestablished with the regular use of Cialis or Viagra. If these fail, injection therapy should be considered (Chapter 11). 

Anemia

TIP causes some degree of anemia, though generally mild. Anemia reverses when the hormone therapy is stopped. If anemia is severe, it can be corrected with medications such as Procrit and Aranesp. Iron is not beneficial for this type of anemia. 

Liver Changes

Casodex, Flutamide, Nilutamide, and Zytiga can occasionally cause liver abnormalities. Monitoring with a hepatic panel blood test needs to be done routinely. 

Mood Swings and Depression

Low doses of an antidepressant medication such as Zoloft, Celexa, or Paxil are very effective at reversing these unpleasant feelings.

Miscellaneous Side Effects

Nilutamide can occasionally cause lung problems. Treatment needs to be stopped immediately if shortness of breath or coughing occurs. Xtandi, in rare cases, causes seizures, so men with a seizure history can’t use Xtandi. Since Zytiga can lower potassium levels, potassium needs to be monitored and supplemented if necessary.  

Weight Gain and Heart Problems

TIP slows metabolism, so weight gain is common. While TIP may not increase the risk of heart disease directly, weight gain causes diabetes and hypertension and both of these can increase the risk of heart disease.

Osteoporosis

Prevention begins with an exercise program. Supplementation with Calcium and Vitamin D is also necessary. Medications such as Xgeva, Zometa, Boniva, Actonel and Fosamax can also be considered. However, these medications have side effects. The most serious is osteonecrosis of the jaw: gum tissue recedes, leaving exposed bone, which is susceptible to recurrent infections. The risk of developing osteonecrosis is much higher when treatment is continued for longer periods or when a tooth is extracted. 

 

Now that the patients with Azure have completed this Section, they can skip ahead to Chapter 43 to finish the remainder of the book.


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.

 

water-blue-ocean.jpg

Azure Subtypes


Azure Subtypes


water-blue-ocean.jpg

Azure Treatments & Side Effects


Azure Treatments & Side Effects


Azure Resources


Azure Resources