BERKELEY, CA (UroToday.com) - Prostate cancer is the most common male cancer in North America. While better screening and treatments have resulted in improved outcomes, a subset of patients eventually develops metastatic disease. Androgen deprivation is highly effective, but eventually resistance develops, leading to a lethal disease phenotype known as metastatic castration-resistant prostate cancer (mCRPC). Traditionally, mCRPC most commonly metastasizes to the bone, and less commonly to other sites. However, coupled with recent regulatory approval of 6 distinctive therapies with different mechanisms of action in the treatment of mCRPC, we have been observing an increasing number of patients now exhibiting disease metastasis at non-osseous sites (e.g., lymph nodes, liver, lung). We thus hypothesize this drug development renaissance has altered the natural history of mCRPC, leading to the emergence of new patterns of metastases.
In our study, we evaluated the pattern of metastatic disease in patients with mCRPC as reported in baseline characteristics of prospective clinical trials from 1990-2012. A total of 290 eligible studies (270 phase II and 20 phase III) involving 19 110 patients were identified. During this time period, rate of non-osseous metastasis increased significantly at +1.6% per year (p < 0.0001), while the rate of osseous metastasis decreased at 0.5% per year (p < 0.0001). The rate of lymph node metastasis increased at 1.4% per year (p < 0.0001), but the rate of liver and lung metastasis remained relatively stable. This observation is important, as awareness and timely recognition of metastatic involvement can lead to improved outcomes in patients with this lethal disease phenotype.
Another major finding from our retrospective analysis was the lack of standardized definitions for reporting baseline extent of disease in patients with mCRPC. 26.8% of the eligible studies failed to report the specific distribution of metastatic sites at baseline. For example, various vague but overlapping terms for metastatic sites were used interchangeably, including “non-osseous metastasis,” “soft-tissue metastasis,” “visceral metastasis,” “measurable disease”, “lymph node disease,” among others. This undermines our ability to better understand the natural history of prostate cancer, and may potentially negatively affect our ability to gain valuable information in clinical trial testing. In our study, we found a notable change in the pattern of metastasis in patients with mCRPC over the past two decades. Evolving patterns of mCRPC are an important but understudied phenomenon that has important implications in treatment selection and prognosis of this lethal disease. It is crucial that future clinical trials of patients with mCRPC define patients with a uniform reporting of metastasis sites. This will then ensure that future studies yield the most accurate results in assessing the pipeline of new therapies entering clinical testing.
Stephanie M. Doctor, Che-Kai Tsao, MD, James H. Godbold, PhD, Matthew D. Galsky, MD, and William K. Oh, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Division of Hematology and Medical Oncology, The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY USA