Treatment and Management of Patients With Prostate Cancer

PSA Screening

William J. Aronson, MD. I’m very encouraged that the U.S. Preventive Services Task Force (USPSTF) has recently drafted revised guidelines for screening men for prostate cancer in which they now are proposing a C grade for prostate specific antigen (PSA) screening in men aged < 70 years. In this age group they now propose an informed discussion with the patient regarding the pros and cons of screening (shared decision making). The USPSTF recommended against PSA screening in men aged ≥ 75 years in 2008 (D grade), and they recommended against PSA screening in all men in 2012 (D grade). Previously the USPSTF put a great deal of emphasis on the PLCO (Prostate, Lung, Colorectal, and Ovarian Screening Trial). In that trial, there was no difference in prostate cancer mortality between the study groups, but, it appears that up to 90% of men in the control group received PSA screening, therefore, invalidating the studies findings.

I still have serious concerns about giving a D grade for men aged > 70 years. Dr. Jim Hu from Cornell University recently published a study in JAMA Oncology and reported that men aged > 74 years now have twice the rate (12%) of presenting with metastatic disease at the time of diagnosis compared with men aged > 74 years prior to the 2008 USPSTF recommendations. In my view, otherwise healthy men with a good life expectancy, even if they’re aged > 70 years, should still have an informed discussion with their physician about getting PSA screening.

Julie N. Graff, MD. I completely agree with Dr. Aronson, and I would add that our veterans are a special group of patients who have risk factors that aren’t seen in the general population. For example, Agent Orange exposure, and I think the VA has not necessarily embraced those recommendations. I’d also add that people are living longer, and most of the men who die of prostate cancer are over the age of 80 years. We need to consider each patient individually and his life expectancy. It’s okay to diagnose someone with prostate cancer, and it’s important to have a conversation about how likely that cancer is to shorten his life and not just turn a blind eye to it.

Nicholas G. Nickols, MD, PhD. I don’t think there’s really anything clinically meaningful about PSA screening that can be gleaned from the PLCO trial. However, there was another trial that looked at PSA screening, the ERSPC (European Randomized Study of Screening for Prostate Cancer) trial, and had less contamination in the nonscreened arm and actually did ultimately show a 27% reduction in prostate cancer mortality in the screened men. We also know that local treatment in men with high-risk prostate cancer actually improves survival. By not screening, men with high-risk disease are going to miss out on potentially curative therapy.

Dr. Aronson. I think other endpoints are crucial to consider beyond just survival. Once patients have metastatic disease that can markedly impact their quality of life. Also, patients who are starting androgen deprivation therapy (ADT) have very significant issues with quality of life as well. I believe these other endpoints should also be considered by the USPSTF.

Jenna M. Houranieh, PharmD, BCOP. The American Cancer Society, ASCO (American Society of Clinical Oncology), NCCN (National Comprehensive Cancer Network), and the American Urological Association all had a different view on screening compared with the USPSTF that I think go more in line with some of the ways that we practice, because they take into consideration life expectancy, patients’ risks, and the age of screening as well.

Active Surveillance

Dr. Aronson. Active surveillance is now a wellestablished, reasonable approach to managing patients with low-risk prostate cancer. When we talk about the various treatment options, we always include a discussion of active surveillance and watchful waiting. Certainly, patients who have a Gleason score of 3+3, a low PSA (< 10) and low volume disease are ideal candidates for active surveillance. There is no established protocol for active surveillance, though there are a number of large series that report specific ways to go about doing it. The key issue for patients is to deemphasize the importance of the PSA, which is a very poor tool for monitoring progression of prostate cancer in men on active surveillance, and to focus on periodically obtaining prostate biopsies.

For patients with prostate cancer who have multiple medical problems and limited life expectancy, there is no reason to do biopsies on a regular basis. Watchful waiting would be more appropriate for these patients. One key issue, which is challenging right now, is that probably the best way to do active surveillance is with the more sophisticated biopsy technology that is now available. That includes both fusing magnetic resonance imaging (MRI) of the prostate into the ultrasound unit we are using to perform transrectal prostate biopsies. The more advanced biopsy units also provide the ability to perform same-site biopsies. There are specific coordinates at each site where a biopsy is performed so that we can go back to that same site on subsequent biopsies. Due to cost issues, these advanced biopsy units are not yet being used at a high frequency.

Dr. Nickols. The large ProtecT trial in the UK randomized men diagnosed with prostate cancer out of a PSA screening cohort to an active surveillance arm, a radical prostatectomy arm, and a radical radiation arm, and has a median of 10 years’ followup. Importantly, the endpoints of overall survival and prostate cancer specific survival were actually the same for all 3 arms, and were quite high. A little more than half of the patients who were on surveillance ended up getting delayed radical therapy of some kind within 10 years.

There was, however, a difference in metastasis-free survival and clinical progression, which were both higher in the active surveillance arm as compared to the treatment arms. Progression to metastatic disease was more than twice as high in the active surveillance arm than the other 2. Most of the patients who had progressed on the active surveillance arm were Gleason 7, and probably were not ideal candidates for active surveillance by today’s standards and would not normally be recommended active surveillance.