Ask the Experts – Martin G Sanda

Question 1. Is there a place for active surveillance in the management of men with intermediate-risk prostate cancer?

Answer
Yes, but only under limited circumstances among some men who have favorable intermediate-risk prostate cancer. Surveillance in this setting really needs to be a consequence of a shared decision-making process. By shared decision-making, what I mean is, the physician informing the patient about the pros and cons of active surveillance (eg avoiding treatment-related symptoms at the risk of cancer progression), and the patient expressing his preferences and priorities related to the trade-offs between symptoms versus reduction of time to prostate cancer metastases or longevity.

The level 1 evidence (based largely on the ProtecT trial from Britain and PIVOT trial from the US) indicates that for favorable intermediate-risk prostate cancer, there is unlikely to be a mortality difference between surveillance and definitive intervention, such as radiation or surgery, in the first 10 years after diagnosis. At 10 years, there may be a higher rate of metastases of the cancer in patients who undertook an active surveillance approach as opposed to those who underwent surgery or radiation, and even though treatment may not eliminate such metastatic disease, it could delay its progression. Some patients might accept a modest increase in risk of metastasis at 10 years as a basis for opting against treatment at initial diagnosis. I think that’s a small minority of patients. A patient with a 10- to 15-year life expectancy might look at active surveillance differently than a patient with a 15- to 20-year life expectancy.

Question 2.  What concerns, if any, do you have about recommending active surveillance for these patients?

Answer
Personally, I don’t view active surveillance as the preferred care option for patients with favorable intermediate-risk prostate cancer. If a patient were to ask me, “Doctor, do you think that with a 15-year life expectancy, should I have treatment or surveillance,” I would recommend treatment, consistent with, for example, the AUA guidelines on this. The recommended and standard care options for favorable intermediate-risk prostate cancer are prostatectomy or radiation. That is what I would endorse as optimal care.

Question 3. Which patients with intermediate-risk PCa would be optimal candidates for active surveillance?

Answer
For patients who really are disinclined to undergo surgery or radiation with hormone therapy, or patients who are particularly averse to possible side effects, who are older or at the less healthy end of the spectrum such that their life expectancy may be closer to that 10- to 15-year rather than the 15- to 20-year time frame, I can see where some of those patients might opt for surveillance.

Surveillance might be safer for patients who have a prostate size of 80 grams or larger, a normal PSA density, less than 0.15, for example, a Gleason score 6 cancer and a PSA level of 10 to 20 ng/mL. In that setting, the PSA level might be less related to the cancer and more to the large prostate. Technically, these patients are in the favorable intermediate-risk category and could be suitable for surveillance.

Other examples of men who might opt for surveillance in a favorable intermediate-risk category are patients in whom the amount of Gleason pattern 4 is very small. Gleason pattern 4 is what leads to the intermediate-risk classification. And in some patients we see a component of pattern 4 as being a 5% or 10% or less of the cancer volume. In fact, some patients may have a very limited cancer volume overall, and yet be deemed intermediate-risk based on the pattern. So if there is a miniscule component of pattern 4, or if MRI or a systematic repeat biopsy confirms that a very small volume cancer, then for those patients surveillance is something that could be a starting point, although I would still counsel those patients that the likelihood that their cancer would progress at some point over the subsequent 5 to 10 years to require treatment is substantial, and that the possibility of the cancer becoming less amenable to cure, with each year of surveillance, is not negligible.

Question 4. Does the new Grade Group system help clarify which men with intermediate-risk PCa are good candidates for active surveillance?

Answer
The new grade group system distinguishes favorable from unfavorable intermediate-risk prostate cancer, which I think is an important distinction, where grade group 3 (ie corresponding to Gleason score 4+3=7) places a man into the unfavorable intermediate-risk category. I think from that perspective, the grade group system is helpful. That’s not to endorse surveillance as a preferred or standard option for favorable intermediate-risk prostate cancer, but just to counsel even more emphatically against surveillance for those with unfavorable intermediate-risk disease. In the favorable intermediate risk category (Gleason score 3+4=7 and PSA less than 10) , again, I think surveillance is a potential alternative to definitive treatment, but is not as optimal for men with life expectancy greater than 15 years.

Question 5. Should active surveillance be more intense for men with intermediate-risk PCa than for those with low-risk disease? If so, how?

Answer
Yes, I think so. Those men are deserving of the utmost vigilance. So, I think, for example, bringing MRI into the picture to gauge the amount of cancer would be important. Doing the PSAs every 3 months as opposed to once or twice a year would be important. Men should not only undergo an initial repeat biopsy in the first year or so, but also additional subsequent rebiopsies at some intervals thereafter.