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ERUS 2018: Salvage Surgery and Treatment of the Primary in Metastatic Prostate Cancer: Need or Search for Indications?

Marseille, France (UroToday.com) This session focused on the treatment of the primary tumor in the setting of metastatic prostate cancer. There is a growing need to improve the treatment of metastatic prostate cancer patients, who currently have an overall survival of only 50% at five years. Therefore, the concept of treatment of the primary tumor has been questioned in this setting to improve survival. Intuitively, treating the primary tumor makes sense due to several reasons:

  1. Reduction of the tumor mass may improve cancer control and increase the effect of systemic therapy
  2. It may reduce the shedding of metastatic cells from the primary tumor
  3. It could reduce the paraneoplastic effect by the primary tumor
  4. Possible reduction of the immunosuppressive effect caused by the primary tumor
In the STAMPEDE trial, long-term hormonal therapy alone was compared to long-term hormonal therapy accompanied by radiotherapy to metastatic lymph nodes.1 A total of 157 patients were analyzed. It was demonstrated that failure-free survival was better among patients receiving radiotherapy with an adjusted hazard ratio of 0.35 (95% C.I 0.19-0.65). The two-year failure-free survival was 89% in the radiotherapy + hormonal arm compared to 64% in the hormonal only arm (Figure 1).

UroToday ERUS2018 Failure free survival in the radiotherapy
Figure 1 – Failure-free survival in the radiotherapy + hormonal arm compared to the hormonal only arm:

Another study analyzed the role of local therapy (either radical prostatectomy[RP] or radiotherapy [RT]) in node-positive patients2. This study assessed 2967 patients who received surgery with hormonal therapy versus patients who received hormonal therapy alone for positive node disease. It was shown that local therapy + hormonal treatment was associated with significant overall mortality (OM) free survival benefit when compared with patients who received hormonal only therapy. At five years, OM-free survival was 78.8% vs. 49.2% in the local therapy + hormonal therapy arm vs. the hormonal therapy only arm, respectively. No significant difference was demonstrated when comparing RP + hormonal therapy to RT + hormonal therapy.

Unfortunately, to date, there is no level one evidence studies on the role of RP in metastatic patients. However, there are several retrospective studies, mainly from large population-based databases, showing an overall benefit (Table 1). One study has shown that the greatest impact of RP is in metastatic prostate cancer patients who have a predicted risk of cancer-specific mortality of less than 50%3 (Figure 2). Other studies have shown a 72-73% reduction in OM and cancer-specific mortality (CSM) in patients treated with RP compared to those who were not. However, these optimistic results cannot replace a randomized controlled study.

UroToday ERUS2018 radical prostatectomy in metastatic prostate cancer patients 1 
Table 1 – Retrospective studies are assessing the role of radical prostatectomy in metastatic prostate cancer patients:

UroToday ERUS2018 metastatic prostate cancer patients benefit the most from radical prostatectomy
Figure 2 – Which metastatic prostate cancer patients benefit the most from radical prostatectomy?

When considering RP in these patients, it is important to remember that these cytoreductive procedures entail a great risk of complications and mortality and at a greater cost, when compared to standard RP4 (Table 2). Additionally, it is currently not clear whether this type of procedure improves the quality of life of these patients. The most recent EAU guidelines state that according to the evidence that we have today, local treatment in metastatic prostate cancer patients should only be used as part of a clinical trial. Fortunately, there are many ongoing clinical trials that will hopefully help us to better assess the role of local treatment in this setting within the next 12 months (Table 3).

In summary, there is a need to improve the treatment of metastatic prostate cancer patients, as mortality is still significant with existent current therapy. Although local treatment, including RP, might have a role, level 1 evidence currently does not exist. Hopefully, in the very near future answers will become available as prospective data will be published.

 
UroToday ERUS2018 Comparison of perioperative outcomes between cytoreductive radical prostatectomy and radical prostatectomy
Table 2 – Comparison of perioperative outcomes between cytoreductive radical prostatectomy and radical prostatectomy for non-metastatic prostate cancer, demonstrating greater morbidity, and costs:

UroToday ERUS2018 Ongoing prospective trials assessing the role of local therapy in metastatic prostate cancer patients
Table 3 – Ongoing prospective trials assessing the role of local therapy in metastatic prostate cancer patients:


Presented by: Nazareno Suardi, Milan, Italy 

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the EAU Robotic Urology Section (ERUS) Meeting - September 5 - 7, 2018 - Marseille, France

References:

  1. James ND, Spears MR, Clarke NW, et al. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial. JAMA oncology 2016; 2(3): 348-57.
  2. Seisen T, Vetterlein MW, Karabon P, et al. Efficacy of Local Treatment in Prostate Cancer Patients with Clinically Pelvic Lymph Node-positive Disease at Initial Diagnosis. European Urology 2017.
  3. Fossati N, Trinh QD, Sammon J, et al. Identifying optimal candidates for the local treatment of the primary tumor among patients diagnosed with metastatic prostate cancer: a SEER-based study. European urology 2015; 67(1): 3-6.
  4. Preisser F, Mazzone E, Nazzani S, et al. Comparison of Perioperative Outcomes Between Cytoreductive Radical Prostatectomy and Radical Prostatectomy for Nonmetastatic Prostate Cancer. European urology 2018.