The recent publication of Phase III trial results examining a possible role for enzalutamide in the management of “castration-resistant prostate cancer” (CRPC) highlights a rarely discussed issue in the oncology literature.1This agent, previously shown in experimental systems to affect the critically relevant androgen receptor pathway in prostate cancer, improved survival in a patient population defined as having “castrate-resistant” disease. In those patients, the median overall survival was 18.4 versus 13.6 months in the placebo “control” arm (hazard ratio, 0.63;P<0.001).
The results of this trial clearly reveal the fact that tumor growth for many patients with CRPC continues to be affected by the biologic activity of hormone-dependent molecular pathways. Therefore, it is reasonable to suggest the term “castrate-resistant,” even though a widely accepted clinical description represents an overly simplistic and possibly quite inaccurate characterization of a particular patient’s prostate cancer at both the clinical and molecular levels.
Unfortunately, this lack of precision in the choice of descriptive terms is not unique to prostate cancer. For example, the malignancy in a woman with epithelial ovarian cancer whose illness has recurred five months and 25 days following the completion of primary platinum-based chemotherapy would be described in most stratification schemas as being “platinum-resistant,” while the same cancer that had been revealed to be present as recently as two weeks later (six months and 10 days) would be stated to be “platinum-sensitive.”
Specific well-defined eligibility and stratification criteria are essential to equalize subjects for randomized clinical trials to ensure balance in the study populations (e.g., platinum-free interval <6 months versus platinum-free interval >6 months, or >12 months, etc.). However, it is also critical to realize that these “definitions” actually may have limited relevance in routine—that is, non-research—disease management.
In fact, one might even suggest that the use of particular descriptive terms (“castrate-resistant,” “platinum-sensitive”) may further confuse, rather than clarify, a given clinical scenario as oncologists attempt to deliver optimal care to individual patients. The selection of more appropriate descriptive terms, even if they are not as simple as those highlighted in this commentary, may be helpful in this regard. For example, one might consider using “predicted platinum–non-responsive (PPNR)” or “low likelihood platinum-responsive (LLPR)” rather than the currently employed definitive but often quite inaccurate expression, “platinum-resistant.”
At minimum, it is critical that those responsible for determining oncologic management fully appreciate the limitations of our shorthand language and not permit such overly simplistic “definitions”—which are often ultimately supported by regulatory agency and insurance company policies—to interfere with the medically appropriate care of their patients.
1. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy.N Engl J Med. 2012;367:1187-1197, PMID: 22894553.