Surveillance for Prostate Cancer: Are the Proceduralists Running Amok?

Debating Dr. Laurence Klotz on active surveillance is a daunting task. He is one of this world’s leading urologists, and certainly one of the best informed on surveillance. Why quibble with Dr. Klotz? All leading academic institutions now have large active surveillance cohorts, and well-attended symposia publically discuss the overtreatment problem in prostate cancer. Brave souls like Dr. Klotz have taken many arrows for leading the charge.

Despite academic leadership, uptake of surveillance among community urologists is hard to discern. In my experience, being treated for low-volume Gleason 6 tumors is the norm, not the exception, for men in the United States. Surveillance may be discussed as an option, but it is not taken seriously. In a recent discussion at a urology group practice, the question was raised, “How many of your prostate cancer patients are under surveillance?” Despite being a busy practice (dominated by robotic surgery), the answer was “nobody.” Why so?

Much discussed by urologic proceduralists is the concept of focal therapy. Why not eradicate the tumor focally and avoid the side effects associated with radical surgery? Good concept, but I am not sure that the discussions are being focused on the right patients. Many discussions focus on procedures (freezing, burning, etc) that eradicate tumors of little clinical consequence. It is hard to leave the prostate alone, especially if you are well armed and trained to attack.

When surveillance is actually practiced today, various entry criteria and algorithms are being utilized. Is a man with three cancerous cores eligible, or should only men with two positive cores be allowed? Some algorithms involve yearly biopsies and some do not, some involve complicated imaging and some do not, some involve lots of prostate-specific antigen (PSA) testing and some do not. What is the best technique? No consensus is apparent; furthermore, there is little consensus on who has “progression” and who does not.

For a brief moment, let us discuss data rather than opinions. There are prospective trials concerning localized prostate cancer. One noteworthy study was SPCG-4,[1] a European randomized study of radical surgery vs observation conducted in patients with disease detected by symptoms (not PSA elevation). Everyone understands radical surgery, but what about observation? Men in the “watchful waiting” group with signs of obstructive voiding were treated by TURP. Bone scan–detected metastases were managed with hormones. Hormonal treatment was also allowed later in the trial if there were “signs of tumor progression” (including elevated PSA level). After a median follow-up of 12.8 years, in patients over age 65, no benefit to surgery was seen in overall survival or prostate cancer–specific survival.[1] Note that complicated surveillance schemes were not used; treatments in the watchful waiting group were typically initiated simply when symptoms were present.

Another prospective trial is PIVOT.[2] There is much to hate about PIVOT, including the fact that the life-expectancy in the enrolled population was suboptimal.[3] Mean age at entry was 67, and recruitment mainly occurred in Veterans Administration hospitals, not the healthiest of populations. In this trial of observation vs radical surgery, “observation” meant that patients were offered various forms of palliative therapy when indicated. After a median follow-up of 10 years, not surprisingly, no differences were seen in overall mortality or prostate cancer–specific mortality in this population. Among those with low-risk disease (PSA < 10 ng/mL and Gleason score of 6 or less, and clinical stage T1c or T2a), there was no trend toward benefit. Other groups trended toward benefit from surgery, but subset analyses were terribly underpowered.

Contrast the observation arms in these prospective randomized trials with how surveillance is being done today: poking, probing, and testing are rampant, while treating for symptoms is viewed as anachronistic. My thesis is that we currently make surveillance too complicated. We do too many biopsies and have unnecessarily complicated algorithms. Too many people are excluded from surveillance in our protocols. Should the vast majority of patients with low-risk prostate cancer simply be followed for symptoms and our procedures held at bay?

Financial Disclosure: Dr. Sartor has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

REFERENCES

1. Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011;364:1708-17.

2. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367:203-13.

3. Sartor O. Radical prostatectomy versus observation for prostate cancer. N Engl J Med. 2012;367:1467.