PROSTATE CANCER MANAGEMENT - Active Surveillance


Active Surveillance at Johns Hopkins: An Evolving Program

A number of advances have led to modifications of our active surveillance program at Johns Hopkins. If you’re a man already enrolled in the program you are aware that a host of factors were assessed about your general health as well as your prostate cancer before entering. Now things have been modified a bit with recent discoveries and advances in the field. There have been modifications both in the selection of men for surveillance, and in monitoring of the cancer.

A podcast featuring Dr. H. Ballentine Carter, director of adult urology at Johns Hopkins, discussing active surveillance is available for you to listen to here

Selection of Men for Surveillance


There are two groups of men in whom active surveillance is considered most appropriate, those at very low risk and those at low risk of disease progression, as outlined below.


RISK PROFILE CRITERIA RECOMMENDATION
Very low PSA <10 Gleason Score <7 and stage T1c and PSA density <0.15 and unilateral disease with <3 cores containing cancer regardless of percent core involvement

Any age if patient prefers surveillance


Preferred if life expectancy is less than 20 years

PSA 10-20 Gleason Score <7 and stage T1c and PSA density <0.10 and unilateral disease with <3 cores containing cancer regardless of percent core involvement

Any age if patient prefers surveillance

Preferred if life expectancy is less than 20 years

Low Stage T1c or T2a and Gleason score <7 and PSA <10

Age >65 years

Preferred if life expectancy is less than 10 years

Intermediate T2 or PSA 10-20 or Gleason score 3+4 Life expectancy is less than 10 year
High Stage T3 or Gleason score >3+4 or PSA >20 Not recommended

 

Gleason refers to Gleason scores.

PSA density is PSA divided by prostate volume determined by ultrasound or MRI (magnetic resonance imaging)

Stage T1c (no abnormality on rectal examination)

Stage T2 (palpable abnormality within prostate)

Stage T3 (palpable abnormality outside prostate)


Let’s take a closer look at each of the categories. 

Primarily men in the very low or low-risk groups are candidates for active surveillance at Johns Hopkins.  Candidates may also include those with intermediate risk disease and limited life expectancy, or those with intermediate risk disease that have a strong preference for avoiding treatment.  The latter two groups may be enrolled provided they understand there is a higher risk of harm without treatment when compared to men with very low to low risk.

Currently, 70% of men in the Johns Hopkins Active Surveillance Program have very low risk disease, and 30% have low risk disease. We recommend that the majority of candidates for the program have an MRI-guided biopsy of their prostate gland to help determine the safety of surveillance (see sidebar).

Fusion of MRI and Ultrasound for targeted biopsies
Advances in computer technology now allow a 3-dimensional rendering of the prostate as imaged by MRI and ultrasound to be aligned or fused. This provides the physician with the ability to target areas of the prostate suspicious on MRI using live ultrasound. As compared to non targeted biopsies that sample the prostate systematically under ultrasound guidance alone, targeted biopsies are more likely to uncover high grade cancers.


The value of targeted biopsies in surveillance is two fold.

First, improving the selection of men that have low grade cancer, by reducing the chance that a high grade cancer was missed on a non targeted biopsy. This may improve the safety of surveillance.


Second, MRI reduces the frequency of monitoring biopsies in those men that have no suspicion of cancer on MRI.

 

MAGNETIC RESONANCE IMAGING (MRI)

Improvements in Magnetic Resonance Imaging (MRI) have led us to incorporate this modality into both patient selection for surveillance and monitoring. Prostate MRI can be used to assess the probability that cancer is present, and the probability that a high grade cancer is present. But MRI cannot diagnose prostate cancer; only a biopsy can do that. Current prostate imaging with MRI relies on multiple parameters (multiparametric or mMRI) to assess this risk.


In general, 3 parameters are used to estimate the likelihood that a cancer is present:

  1. the tissue signal intensity (T2 weighted images)
  2. how well water diffuses through the tissues or diffusion weighted imaging (DWI)
  3. the extent to which contrast material is taken up by tissues and washes out of the tissues (dynamic contrast enhancement or DCE)


As compared to normal tissues, prostate cancer is associated with low signal intensity, low water diffusion, and earlier contrast enhancement with faster washout of contrast. At Johns Hopkins, radiologists use the PI-RADS (prostate imaging reporting and data systems) grading system from 1-5 based on the mMRI. The grading system corresponds to the suspicion that cancer is present:
  • grade 1-2 (low suspicion)
  • grade 3 (indeterminate)
  • grade 4-5 (high suspicion)
The probability that a high grade cancer is present increases as the MRI grade of the lesion increases from 1-5.


Very low-risk:  Characteristics of a man considered to be at very low risk for progression of his prostate tumor would include a low prostate specific antigen density (PSAD; see sidebar) indicating that his PSA is appropriate for the volume of the prostate, a Gleason score (see sidebar) of less than 7, less than 3 cores of tissue from the biopsy showing cancer, and unilateral cancer (cancer found on only one side of the prostate either right or left (see modified Epstein criteria).  Surveillance would be the preferred option for these men if life expectancy is less than 20 years, which would include most men over age 65 years.


Low-risk: Characteristics of a man considered to be at low risk for progression of his prostate tumor would include a Gleason score of less than 7, a PSA measurement of less than 10, and stage T1c or T2a disease. Surveillance would be the preferred option for men with low risk prostate cancer that have less than a 10 year life expectancy; and should be considered for men over age 65 years.


Modified Epstein Criteria

In 1994, Jonathan Epstein and colleagues at Johns Hopkins described the prostate biopsy criteria for predicting the presence of a small volume low grade cancer within prostates removed surgically for treatment of prostate cancer.

The idea was to identify men that could safely forego surgery and enroll in active surveillance before removing the prostate.

The criteria that were predictive of small volume (cancer less than 0.5cc) and low grade (Gleason score 6) prostate cancer at radical prostatectomy were a PSA density below 0.15, and a prostate biopsy showing low grade cancer (Gleason score 6) that was small volume on biopsy (no more than 2 cores with cancer and no more than 50% involvement of any tissue core involved with cancer).

In a study published in 2014 the original criteria have been modified with the presence of a unilateral cancer (cancer on only one side of the prostate either right or left) replacing the percentage of the tissue core involved with cancer. The current criteria that are referred to as very low risk include a PSA density below 0.15, Gleason score 6 on prostate biopsy, no more than 2 cores of tissue with cancer that is located on one side of the prostate on biopsy.

Men who meet these criteria are considered at very low risk of harboring aggressive prostate cancer and could be considered the most ideal candidates -but not the only candidates -for active surveillance.

Men who would like to participate in active surveillance must also be comfortable living with a 'wait and see' approach, knowing they are being carefully monitored so that physicians are prepared to intervene immediately if the tumor becomes more threatening, and also men who want to avoid consequences of treatment that may include urinary incontinence and sexual dysfunction.

What’s required for follow-up? Periodic measurements of PSA and prostate biopsies are necessary. If the PSA rises rapidly or there are changes the pathologist identifies on the biopsy that indicate rapid progression, these would be triggers for further evaluation and possibly intervention.

What are the risks of participating in active surveillance?
Your risk of undetected prostate cancer progression is extremely low. Risks that have been identified in some programs largely result from misclassification of your tumor at the time of diagnosis, where the cancer is aggressive and associated with death from prostate cancer at 15 years after treatment. Current literature suggests that this may occur in 2-3% of cases. Right now a host of molecular markers and imaging techniques are in development to reduce this number further.

Prostate Specific Antigen Density or PSAD

PSAD is the ratio of the PSA level and the prostate size as measured by ultrasound or MRI (PSA/prostate volume). PSAD is one of the strongest predictors of cancer volume and therefore the aggressiveness of the cancer. Most men with small volume low grade cancers will have a PSAD below 0.15ng/ml per cc. Or thought of another way, men with a PSAD below 0.15 are more likely to have low volume and low grade prostate cancer.

Gleason Grades (patterns) and Scores



The architecture of prostate glands within a prostate cancer is closely associated with cancer aggressiveness –an observation made by the pathologist Donald Gleason in the 1960’s. Today, the Gleason grading system is the most accurate method of determining cancer aggressiveness. When I explain the Gleason grades to patients, I use the analogy of furniture in a room, with the furniture representing the prostate cancer gland architecture and the room representing the prostate gland. Low grade cancers are orderly rooms with furniture arranged normally. Poorly differentiated cancers are like the fraternity house room after a fraternity party on Saturday night –disorderly to say the least.


Pathologist used to assign Gleason grades or patterns from 1 to 5 by looking at tissue from a prostate cancer under the microscope, with lower grades representing more normal appearing prostate architecture and higher grades representing disorderly architecture. Today, pathologists do not assign the grades 1 and 2, but only 3-5, because grades 1 and 2 are not seen on prostate biopsies. Grade 3 is considered to be low grade or well differentiated and more orderly, whereas grades 4 and 5 are considered high grade and less orderly patterns. Prostate cancers are sometimes made up of more than one grade or pattern. Pathologists view the cancer tissue microscopically and assign a grade from 3-5 to the most prominent pattern and another grade of 3-5 to the second most prevalent pattern. This system results in a Gleason score ranging from 6-10, with Gleason 6 cancer considered low grade, and 7 and above considered as high grade. The higher the Gleason score the more aggressive the cancer. However, a Gleason score of 4+3=7 would be more aggressive than a score of 3+4=7, because the prominent grade or pattern in the 4+3 would be 4 as compared to 3+4 where the prominent pattern is 3.


The Gleason system is often confusing to patients who hear they have a Gleason score of 6 and consider this to be high; whereas in reality it is the lowest Gleason score. To help patients understand more about the nature of their particular cancer, the pathology department at Johns Hopkins includes a prognostic score (not Gleason score) from 1-5 (5 being the most aggressive cancer) with every pathology report (see below). Men in the prognostic group of 1 should take comfort that they do not have a life threatening or urgent situation that needs treatment immediately and may never need to be treated depending on life expectancy and other factors.


PROGNOSTIC GRADE GROUPS AND GLEASON SCORES

 GLEASON SCORE

PROGNOSTIC GROUP (on a scale of 1 to 5)

 6*

 1*

 3+4

 2

 4+3

 3

 8

 4

 9 and 10

 5

*A man’s risk of death as a result of prostate cancer is similar whether treated or not over 10-15 years after diagnosis if associated with low clinical stage (T1c or T2a) and a PSA below 10ng/ml.