David F. Penson, MD, MPH, is Professor and Chair of the Department of Urologic Surgery at Vanderbilt University Medical Center in Nashville, Tenn. He is director of the Center for Surgical Quality and Outcomes Research in the Vanderbilt Institute for Medicine and Public Health. His primary research interest is in population-based cohorts and assessing patient-reported outcomes in conditions treated with surgical procedures, specifically prostate cancer. Renal & Urology News asked Dr. Penson for his views about key recent developments in prostate cancer management.
If you had to pick the most important advance in prostate cancer management in the past 10 years, what would it be?
Dr. Penson: I think the most important advance we have seen in the past decade in prostate cancer management has been the discovery and approval of numerous agents that have been shown to prolong survival in castrate-resistant disease. While none of these individual agents is “curative” on its own, all represent important steps in that direction. I can only imagine what will happen when we start combining therapies and adding other newly discovered agents.
A number of studies have demonstrated that multiparametric MRI can improve the accuracy of prostate cancer detection. Should clinicians use it routinely in the diagnostic work-up if it is available?
Dr. Penson: I completely agree that MRI has become an important adjunct to prostate biopsy that is improving our ability to detect prostate cancer. This is particularly true when the MRI is used in conjunction with ultrasound to perform a so-called fusion biopsy. I don’t know if we should be using it routinely in all men at risk for prostate cancer, however. This may not be the most cost-effective way to approach prostate cancer detection. In my practice, I try to reserve MRI-fusion TRUS [transrectal ultrasound] biopsy for men who have a rising PSA and a prior negative TRUS biopsy or men who I am following on active surveillance. I am particularly excited about MRI as it is applied to active surveillance, as it may ultimately allow us to avoid some repeat biopsies. That being said, we still need more research in this space.
It remains unclear whether robotic-assisted radical prostatectomy (RARP) results in better oncologic control, but evidence suggests this approach offers advantages over traditional surgery in terms of recovery of potency and urinary continence. Do these advantages by themselves justify the preferential use of RARP?
Dr. Penson: At this point, the question is effectively moot. Roughly 85%-90% of prostatectomies performed in the U.S. use the robotic-assisted laparoscopic (RALP) approach, so from a purely quality of care perspective, RALP is preferred because it is the usual approach of most urologists in 2015.
Does the current evidence support the use of intermittent over continuous androgen deprivation therapy (ADT) in men with advanced prostate cancer who require ADT?
Dr. Penson: I really feel as though the jury is still out on this one. The results of the SWOG study of men with metastatic disease (Hussain et al, N Engl J Med 2013;368:1314-1325) couldn’t rule out the inferiority of intermittent ADT when compared with continuous ADT. In other words, it is possible that intermittent ADT may not work as well. Conversely, in the Canadian trial of men with biochemical failure M0 disease only (Crook et al, N Engl J Med 2012;367:895-903), the results documented that intermittent therapy was statistically non-inferior to continuous treatment. To translate the results out of statistical-ese and into somewhat plain English, it is probably still best to treat men with documented metastatic disease with continuous ADT. In the case of M0 disease (biochemical failures), however, intermittent therapy is certainly a reasonable choice and may even be superior in terms of cardiovascular-event rates and quality of life outcomes.
Would you consider using active surveillance for selected men with intermediate-risk prostate cancer, and if so, what would be the selection criteria?
Dr. Penson: I remain reluctant to endorse active surveillance in intermediate-risk disease. Simply put, many and perhaps the majority of these cancers are clinically significant, and patients might realize a benefit from aggressive intervention as early as possible. The advent of genomic testing may change this over the next few years. But right now, I don’t recommend active surveillance to my patients with intermediate-risk disease.
In your view, what is the most critical study in prostate cancer management that has yet to be conducted?
Dr. Penson: There are so many studies that need to be done. A big part of the problem is that they take so long to complete that researchers are not willing to undertake them. Rather than focus on a particular study, I will state that the greatest need for research is in the patient who has biochemical recurrence after primary therapy. We have no idea when to treat these patients, or do we know how best to treat these patients. This is a big segment of the prostate cancer population, and it’s clear that many biochemical recurrences are clinically indolent, so any information to guide treatment here would be highly impactful.
Is there a place for surgery as a salvage therapy for prostate cancer patients who experience biochemical recurrence after primary radiotherapy?
Dr. Penson: Yes, there is but it’s the great minority of patients in my opinion. In my practice, I reserve salvage prostatectomy for younger patients with biopsy-proven higher-grade localized disease recurrence.
What do you predict will be the most important game changer in prostate cancer management in the next 10 years?
Dr. Penson: Additional novel medical therapies to treat prostate cancer and earlier use of the existing medical therapies. I think we have gone as far as we are going to go in the treatment of localized disease with surgery or radiation, but we are just scratching the surface with regard to medical treatment of this common malignancy. There is surely more to come in the next decade which will really help our patients.
David F. Penson, MD, MPH, is Professor and Chair of the Department of Urologic Surgery at Vanderbilt University Medical Center in Nashville, Tenn.