Prostate Cancer Risk Assessment: A Sensible Guide To Appropriate Treatment

Andrew Siegel MD  6/22/19

To determine the most appropriate and effective prostate cancer management strategy, newly diagnosed patients are “risk stratified” to predict the cancer’s potential for aggressiveness and severity. Today’s entry explains the means of this process.

Each case of prostate cancer is unique and has a variable biological potential for progression, spread and death. Prostate cancer can be “triaged” into low, intermediate and high risk categories.  Many cancers are “indolent” (low risk) requiring no treatment aside from careful monitoring, while some at the other end of the spectrum are so highly aggressive (high risk) that they incur the prospect of metastatic disease and cannot be cured (but can be well managed), and many lie in the middle (intermediate risk), in which there is the potential for death from prostate cancer and benefit from treatment, which is often curative.

Classification of prostate cancer into risk categories is based upon the following factors: tumor stage, Gleason score, volume of cancer on biopsy, PSA and PSA density, and at times, genomic testing. Additional factors that influence treatment choices for prostate cancer are: age, life expectancy, health status, presence or absence of urinary symptoms and personal preferences.

The extent of prostate cancer—whether localized, regionally advanced or metastatic—is an important factor that informs treatment. Extent or “staging” is determined by digital rectal exam and magnetic resonance imaging; additionally, computerized tomography and bone scan are often obtained to stage unfavorable intermediate risk and higher risk prostate cancer.

Tumor staging

The TNM (Tumor/ Lymph Nodes/ Metastases) system is used to determine the stage of prostate cancer. T refers to tumor size; N the extent of lymph node involvement; and M to the presence or absence of metastasis (spread).

Prostate cancer diagnosed because of a PSA elevation without the presence of an abnormality on digital rectal examination (DRE) is a different tumor category than one diagnosed because of an abnormality on DRE. This is because the presence of palpable cancer (one that can be felt on DRE) indicates that the cancer is already close to the capsule—perhaps beyond the capsule—whereas non-palpable cancer is typically earlier in the natural course of cancer progression.

Stages of prostate cancer (Image from PROSTATE CANCER 20/20:  A Practical Guide To Understanding Management Options For Patients And Their Families)

Stage T1

Tumor is microscopic and confined to the prostate and not apparent on DRE. T1a is tumor found incidentally in prostate tissue removed because of symptomatic enlargement (< 5 % of prostate tissue removed); T1b is tumor found incidentally in prostate tissue removed because of symptomatic enlargement (> 5 % of prostate tissue removed); T1c is tumor identified by biopsy because of PSA elevation or acceleration.

Stage T2

Tumor is confined to the prostate and is detected by DRE.  T2a involves less than half of one side of the prostate; T2b involves more than half of one side; T2c involves both left and right sides of the prostate.

Stage T3 or T4

T3a tumors extend beyond the prostate capsule, sparing the seminal vesicles; T3b tumors invade the seminal vesicles. Stage T4 tumors have spread to organs near the prostate, but within the pelvis, e.g., bladder, rectum or pelvic sidewall.

Stage N+ or M+

Cancer has spread to pelvic lymph nodes (N+) or to lymph nodes, bones, and/or organs distant from the prostate (M+).

Gleason Score

Dr. Gleason devised a clever system that microscopically grades prostate cancer based upon cellular architecture. He recognized that prostate cancer grade is the most reliable indicator of the potential for cancer growth and spread. The grading system that bears his name provides one of the best guides to prognosis and treatment.

To determine Gleason score, the pathologist assigns a separate numerical grade to the two most predominant architectural patterns of the cancer cells, the first number representing the grade of the primary (most predominant) pattern and the second number representing the grade of the secondary pattern. The grades range from 3 (just over the threshold for cancer) to 5 (the cells that have the most cancerous appearance). The sum of the two grades is the Gleason score. The lowest possible score is 6; the highest is 10. The Gleason score predicts the aggressiveness and behavior of the cancer, with higher scores having a worse prognosis than lower scores.

Gleason score is one of the most important factors to be considered prior to making an informed treatment choice. Whereas men with low Gleason scores are often candidates for active surveillance, a high Gleason score mandates more aggressive management.

There are 5 Gleason Grade Groups based upon Gleason score:

Grade Group 1 (Gleason score 3+3=6)

Grade Group 2 (Gleason score 3+4=7)

Grade Group 3 (Gleason score 4+3=7)

Grade Group 4 (Gleason score 4+4=8 or 3+5=8 or 5+3=8)

Grade Group 5 (Gleason score 4+5=9 or 5+4= 9 or 5+5=10)

To help understand the significance of the Gleason score, the rates of undetectable PSA five years after surgical removal of the prostate in Grade Groups 1-5 are the following: 96%, 88%, 63%, 48%, and 26%, respectively.

Number cores with cancer

Generally, at least 12 biopsy cores are obtained and the number of cores that have cancer can provide invaluable information to help guide treatment. The more cores that contain cancer, the greater the volume of cancer and the greater the risk.  A man who has 12/12 cores with cancer has a very different disease than a man with 1/12 cores with cancer.

Percent tumor involvement (PTI)

The percentage of cancer in each cancer core is also useful information. In general, the greater the PTI, the greater the risk. A man with cancer in 3/12 cores that involves 100% of each core has a very different disease than a man with cancer in 3/12 cores that involves 5% of each core.

PSA and PSA velocity

PSA is a superb tumor marker for men with prostate cancer. In general, the lower the PSA, the greater the chance of localized (organ-confined) cancer and conversely, the higher the PSA, the greater the chance of non-localized cancer.  The lower the PSA, the greater the likelihood of cure with surgery or radiation therapy.  Men with a PSA higher than 20 have a greater risk of locally advanced or metastatic disease and a higher likelihood of failing surgery or radiation therapy.

PSA velocity (rate of change over time) also provides essential prognostic information. A high PSA velocity preceding the diagnosis of prostate cancer is associated with a poorer prognosis.

PSA density (PSAD)

PSAD is the relationship of PSA to the size of the prostate, determined by dividing PSA by the prostate volume. The volume of the prostate is easily determined by ultrasound or by MRI (magnetic resonance imaging). A PSA density > 0.15 is considered to be a higher risk.

Genomic testing

Genomic biomarkers have become an increasingly popular tool for risk stratification. Oncotype DX (genomic prostate score) is one such assay that determines the expression of 17 genes. It is often used for newly diagnosed Gleason 6 (3+3) and 7 (3+4) cancers to help determine who will benefit from active surveillance vs. surgery or radiation.

Age and life expectancy

The prevailing view accepted among prostate cancer experts is that the more years one has left to live, the greater the likelihood that surgery will provide the greatest chance of achieving that potential. So, if you are 43 years old and in perfect health, the most prudent option is often a radical prostatectomy. On the other hand, if you are elderly and have a less than ten-year life expectancy, you likely will not need any treatment as other more pressing medical issues may cause your demise before the prostate cancer has a chance to.

With respect to age, I refer to “physiological” age as opposed to “chronological age.”  In other words, not how many years per se that you have lived on the planet, but at what age you are functioning and how many years you may be expected to live.  Of two men who are chronologically 65 years old, one may be functioning like a 55-year-old and the other as an 80-year-old, and treatment needs to be tailored accordingly.

As surgery and radiation have competitive 15-year results and the demands and potential side effects of surgery are greater than that of radiation, at a certain age, radiotherapy becomes a more prudent consideration.

Health status

If you are not in good health and do not have an expected ten-year life expectancy, there is usually no compelling reason to treat the prostate cancer as other health issues are likely to be of more concern than the prostate cancer.

In general, surgery should be reserved for healthy men who can tolerate an invasive surgical procedure and the general anesthesia necessary to undergo it. If your health is compromised, but you have a greater than ten-year life expectancy, radiation becomes a sensible management option.

Urinary symptoms

Benign prostate enlargement commonly accompanies aging, paralleling the increasing prevalence of prostate cancer with aging. As the prostate enlarges, it often—but not always—squeezes the urethral channel, making urination difficult and resulting in annoying symptoms and sleep disturbance.  An enlarged prostate can act like a hand squeezing a garden hose, compromising the flow through the hose. The situation can be anything from a tolerable nuisance to one that has a huge impact on one’s daily activities and quality of life.

The presence of Lower Urinary Tract Symptoms (LUTS) can be an important factor in guiding treatment options.

 Obstructive LUTS consist of the following:

hesitancy—a stream that is slow to start

weak stream—a stream that lacks force

narrow stream—a thin stream

intermittency—a stream that starts and stops

straining—the need to use abdominal muscles to urinate

prolonged emptying time—excessive time to empty the bladder

incomplete emptying—inability to empty the bladder

Irritative LUTS consist of the following:

frequency—urinating more often than normal

nocturia—awakening from sleep to urinate

urgency—the sudden and strong desire to urinate

precipitancy—the need to get to the toilet in a hurry

urgency incontinence—the sudden and strong desire to urinate with the inability to get to the toilet in time to prevent leakage

The presence or absence of LUTS can be an important factor to help guide the most appropriate treatment options. For example, if a man diagnosed with prostate cancer has significant LUTS, a prostatectomy may be the best management option to treat both the cancer and the annoying symptoms, as opposed to radiation therapy that can worsen the LUTS.

Personal preferences

Our intention as urologists is not to dictate exactly what approach to take, as there are usually several competing management options, but to provide education, direction and guidance through the options, offering sensible and pragmatic advice based upon our knowledge and experience.

I truly believe in the FBSU test (Father, Brother, Son, Uncle test)— giving patients the same advice I would give to family members. Every man has different circumstances, priorities, medical issues, life expectancies and concerns about the side effects of treatment alternatives.  Recognizing this, the opinions of the patient, family members and loved ones who have a clear understanding of the management options are of paramount importance in the ultimate choice of a treatment.  The goal of this collaborative and shared decision-making process between patient and physician is to optimize medical decisions by helping patients choose the option they feel most comfortable with.

RISK CATEGORIZATION (This strategy is based upon the National Comprehensive Cancer Network guidelines)

Integrating the factors of tumor stage, Gleason score, cancer volume, PSA and PSA density, supplemented with genomic testing, an individual case of prostate cancer can be assigned to one of five risk categories ranging from very low risk to very high risk. This risk categorization is helpful in predicting the future behavior of the prostate cancer and in the management decision-making process.

The following are the five risk groups and the criteria for membership in each:

Very Low Risk: T1-T2a; Gleason score 6; fewer than 3 cores with cancer; PTI less than 50% of cancer in each core; PSA < 10; PSA density < 0.15

Low Risk: T1-T2a; Gleason score 6; more than 3 cores with cancer; PTI greater than 50% of cancer in any core; PSA < 10

Intermediate Risk: T2b-T2c or Gleason score 7 or PSA 10-20

Within the intermediate risk category, further sub-stratification is as follows:

      Favorable Intermediate Risk:

T1-T2a, Gleason score 6, PSA 10-20

T1-T2a, Gleason score 7 (3+4), PSA < 10

      Unfavorable Intermediate Risk:

T2b, Gleason score 7 (3+4), PSA < 10

T1-T2, Gleason score 7 (3+4), PSA 10-20

T1-T2, Gleason score 7 (4+3), PSA < 20

High Risk: T3a or Gleason score 8-10 or PSA > 20

Very High Risk: T3b-T4 or Gleason grade 5 as the predominant grade (the first of the two Gleason grades in the Gleason score) or > 4 cores Gleason score 8-10

Coming next week…An overview of prostate cancer treatment options based upon risk assessment.

Wishing you the best of health,

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Dr. Andrew Siegel is a physician and urological surgeon who is board-certified in urology as well as in female pelvic medicine and reconstructive surgery.  He is an Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community. He is a urologist at New Jersey Urology, the largest urology practice in the United States.

The content of this entry is excerpted from his new book, PROSTATE CANCER 20/20: A Practical Guide to Understanding Management Options for Patients and Their Families

Video trailer for Prostate Cancer 20/20

Preview of Prostate Cancer 20/20

Andrew Siegel MD Amazon author page

Prostate Cancer 20/20 on Apple iBooks

Dr. Siegel’s other books:

FINDING YOUR OWN FOUNTAIN OF YOUTH: The Essential Guide to Maximizing Health, Wellness, Fitness and Longevity

PROMISCUOUS EATING— Understanding and Ending Our Self-Destructive Relationship with Food

MALE PELVIC FITNESS: Optimizing Sexual and Urinary Health

THE KEGEL FIX: Recharging Female Pelvic, Sexual, and Urinary Health

 

 

Tags: Andrew Siegel MD, prostate cancer, Prostate Cancer 20/20, prostate cancer risk assessment