For the September and October issues of ONCOLOGY, we have assembled a team of experts in the diagnosis and management of early-stage prostate cancer—ie, disease that has not clinically metastasized at first presentation, and which is theoretically curable—and have asked them to take a position on optimal patterns of care. This has been a topic of great controversy for decades, and the choice of optimal therapy has constituted a real challenge for most patients. All of these nationally renowned clinician investigators would normally seek some measure of middle ground; however, we have asked them to be deliberately polemical, and to help to frame the debate for those of us who, in turn, have to advise our patients.
This month, Amin Mirhadi and Howard Sandler defend the position that “Radical Radiotherapy for Prostate Cancer Is the Only Way to Go,” while Heidi Rayala and Jerome Richie maintain, “Radical Prostatectomy Reigns Supreme.” In next month’s ONCOLOGY, Jay Ciezki and Eric Klein consider, “Brachytherapy or Surgery? A Composite View,” and Michael Large and Scott Eggener address “Active Surveillance for Low-Risk Localized Prostate Cancer.” These articles are accompanied by brief commentaries from other noted physicians in the field, including Edward Schaeffer and Stacy Loeb; Deborah Kuban; Joseph Aronovitz and Martin Sanda; and David Penson.
In my view, these manuscripts elegantly indicate that there are not vast differences in survival between the results of surgery or radiotherapy, but that the differences in toxicity are real, and clear understanding of these differences should be important in the decision process for patients. It is clear that many clinicians are inaccurate when reporting patient perceptions of toxicity, and we should increasingly be developing algorithms to quantify these toxicities.[1]
An emerging oddity is the proportion of urologists in clinical practice who have recently taken a 180° change in direction, altering their practices from emphatic emphasis on radical prostatectomy to the purchase of radiotherapy equipment and hiring of radiation oncologists to supervise delivery of this treatment. As noted in the commentary from David Penson, active surveillance is not just idle watching, and is a very reasonable option that should be considered carefully, especially in light of some of the randomized screening trial data discussed below.
Uneven Progress
The field of prostate cancer has been advancing rapidly in some domains, and with less clarity and speed in others. For example, important work is being done to unravel the causation and epidemiology of the disease, with creative gene-mapping,[2] investigation of viral etiology,[3] and studies of the impact of stroma and many other factors.[4] These developments will eventually influence our management of early-stage disease. We are coming to understand the importance of tumor heterogeneity in confounding some management pathways,[5] and thus, the importance of multidisciplinary management.
In particular, it appears that we are altering the natural history of stage C disease, when managed by radiation or surgery, provided that these local modalities are combined with androgen-suppression therapy.[6-9] Of equal importance, it is becoming clear that androgen suppression has its own costs, most specifically the evolution of metabolic syndrome, depression, impaired bone health, and psychosexual consequences, and chemotherapy also may have unanticipated late effects when used in the adjuvant setting for prostate cancer.[10] Thus, there is a real need to anchor each proposed new step with randomized clinical trials that assess outcomes and toxicities carefully.
In developing new drugs, either for advanced disease or the adjuvant setting, an important challenge remains—specifically, to define an optimal surrogate marker of true utility in order to enable increased speed of drug development without the loss of accuracy. The US Food and Drug Administration has been struggling with this for years. In advanced disease, prostate-specific antigen (PSA) response has been studied extensively,[11,12] but this measurement is imperfect and often inaccurate. Similarly, patient-reported outcomes focused on symptoms and well-being are confounded by methodologic flaws and limitations.[13]
