By Mark Scholz, MD
By Mark Scholz, MD
Once the proper Stage of Blue is assigned ,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, commonly known as “active surveillance,” is the process of monitoring the cancer while reserving medical intervention until some aggressive behaviour is detected.
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.
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.
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.
A board-certified medical oncologist, Mark C. Scholz, MD, serves as medical director of Prostate Oncology Specialists Inc. in Marina del Rey, CA, a medical practice exclusively focused on prostate cancer. He is also the executive director of the Prostate Cancer Research Institute. 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 the co-author of the book Invasion of the Prostate Snatchers: No More Unnecessary Biopsies, Radical Treatment or Loss of Potency. He is a strong advocate for patient empowerment.
By Stanley Brosman, MD
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.
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.
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.
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
By Jonathan Epstein
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.
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?"
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.
By Daniel Margolis, MD
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 (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.
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
By Duke Bahn, MD
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 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.