BETHESDA, MD USA (UroToday.com) - Dr. Howard Scher discussed use of radical prostatectomy (RP) in patients with limited metastatic disease via a multidisciplinary approach. He started by emphasizing that this approach is not appropriate for all patients with metastatic disease, but there may be a subset of patients who could benefit from removal of the primary tumor in the setting of metastatic disease. He discussed that the current literature looking at RP in this setting is very heterogenous, with wide variations in the populations studied, including patients with nodal disease only, bony disease with or without nodal disease, or, uncommonly, even limited visceral disease. Objectives assessed in these studies are also varied, ranging from local control and the prevention of local symptoms to cytoreduction or prolongation of survival. Another significant limitation of the current literature on the benefit of surgery in the setting of metastatic disease is that the majority of the published studies are retrospective and non-randomized.
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In building a case for the potential benefit of local therapy in patients with metastatic disease, Dr. Scher pointed to SEER data which demonstrated a 5-year cancer-specific survival (CSS) benefit in patients undergoing RP or brachytherapy in the metastatic setting (76% or 61% 5-year DSS, respectively, compared to 49% in patients without local therapy). He then discussed a study released earlier this year looking at RP vs no RP in patients demonstrating a response to androgen deprivation therapy (ADT) which found longer time to development of castrate-resistant prostate cancer (CRPC), and time to clinical progression as well as increased CSS in patients undergoing RP.
In building a case for the potential benefit of RP for cytoreduction, Dr. Scher pointed to the benefits seen in other cancer types including breast cancer, colorectal cancer, renal cell carcinoma, and ovarian cancer. With the new systemic therapies demonstrating an inverse relationship between outcomes and disease burden (i.e., better outcomes with less disease and vice versa), treatment of prostate cancer could conceivably parallel that of ovarian cancer where maximal debulking is standard. He pointed to the fact that patients receiving neoadjuvant ADT rarely ever demonstrated complete resolution of their primary tumor, suggesting that systemic therapy is not adequate for its treatment.
He then presented two anecdotal cases of patients with limited bony metastatic disease in whom the use of surgery and radiation for local control, in addition to intermittent ADT, resulted in a durably low PSA off ADT.
He next looked at alternative systemic therapies which could, when coupled with definitive local therapy for the primary prostate tumor, potentially result in a cure for metastatic prostate cancer. Ipilimumab administration in advanced melanoma has been demonstrated to result in durable long-term responses in a small proportion of patients, suggesting that these patients could be considered “cured” of their disease. Thus, ipilimumab is a provocative candidate for use in a multidisciplinary approach with surgery to attempt to “cure” very select patients with metastatic prostate cancer. Dr. Scher spoke about a study currently underway at MSKCC examining the efficacy of ipilimumab in concert with degarelix and radical prostatectomy in the treatment of metastatic prostate cancer. He finished his talk by outlining additional phase III studies looking at the possible benefit of local therapy in metastatic prostate cancer, including a study at MD Anderson looking at the use of RP in patients who demonstrate a response to ADT, and the STAMPEDE trial in the UK looking at the combination of ADT for systemic disease and radiation therapy for local control.
To date, the evidence for RP in the setting of metastatic disease is insufficient to make any definitive conclusions. While removal of the primary tumor, which serves as a potential reservoir for additional metastatic disease, seems logical in the setting of very limited distant disease, adoption of such an approach will rely on the development, via a prospective, randomized trial, of an optimal strategy utilizing a multidisciplinary approach.
Howard I. Scher, MD
Memorial Sloan-Kettering Cancer Center, New York, NY USA
Timothy Ito, MD* from the 2014 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" - December 3 - 5, 2014 - Bethesda, MD USA
*Fox Chase Cancer Center, Philadelphia, PA USA