EAU PCa 17: Treatment of Oligometastatic Disease

Vienna, Austria (UroToday.com) At this afternoon’s EAU Update on Prostate Cancer in Vienna, Austria, Dr. Maurizio Brausi from Italy provided an excellent contemporary update on the treatment of oligometastatic prostate cancer. Dr. Brausi started with a definition of oligometastatic disease, which he states is an intermediate state of tumor spread with limited metastatic capacity. Specifically, this entity appears to include loco-regional spread with better prognosis than systemic spread, or low volume metastatic disease with better prognosis. According to Dr. Brausi, the implication of oligometastatic treatment is that some patients in this state could be cured with definitive directed therapies. 

Since the introduction of anatomical and functional imaging with MRI, choline-PET, and PSMA-PET, oligometastatic disease is increasingly diagnosed. Emerging genomic data have suggested distinct biological differences between limited metastatic lesions and widely disseminated disease. In Dr. Brausi’s opinion, it may be possible to delineate between which are clinically apparent oligometastatic lesions and what are manifestations of a more widespread process. Dr. Brausi breaks down the treatment of oligometastatic prostate cancer into three distinct categories:

(i) Systemic Therapy 

Over the last several years, in addition to ADT for systemic therapy of oligometastatic disease, there is level 1 evidence for adding either docetaxel [1-3] or more recently abiraterone [4-5]. Furthermore, a systematic review and meta-analysis of patients receiving docetaxel found a 10% absolute improvement in survival (from 40-50%) at 4 years [6]. As Dr. Brausi notes, in the most recent version of the EAU guidelines [7], docetaxel combined with ADT is THE standard of care for first line treatment of metastatic prostate cancer. Certainly, patients must be fit for docetaxel chemotherapy, which has implications for age, performance status, as well as cardiovascular, renal, and hepatic comorbidities. 

(ii) Local Therapy of the Primary Tumor

Dr. Brausi notes that there are several prerequisites for a successful radical prostatectomy in the setting of oligometastatic disease, including accurate imaging to detect early metastases, complete resectability of the primary tumor, and acceptable morbidity. Culp et al. [8] in a study of the SEER database, found 8185 men with metastatic prostate cancer at the time of diagnosis, of which 245 underwent a radical prostatectomy and 129 men underwent brachytherapy. When assessing for prostate cancer specific mortality, adjusting for age, PSA, T-stage, tumor grade, and year of diagnosis, there was a significant improvement for those receiving local therapy to the prostate compared to those receiving ADT only. Radical prostatectomy was associated with decreased cancer specific mortality in all M-stages while brachytherapy improved cancer specific morality in M1c disease. An assessment of 1,538 patients with metastatic disease undergoing radical prostatectomy in the Munich Cancer Registry assessed overall survival [9], finding similar results to the Culp SEER study. The EAU guidelines recommends consideration of radical prostatectomy in ‘highly selected’ men with cT3b-cT4 cN0 or cTx and c/pN1 prostate cancer [7]. Furthermore, an extended lymph nodes dissection should always be performed in high-risk patients and for those with lymph node involvement. However, Dr. Brausi notes that there is no recommendation concerning local therapy for distant metastasis, noting that the guideline standard of care is still ADT. According to a recent study by Heidenreich et al. [10], inclusion criteria for cytoreductive prostatectomy in men with low volume skeletal metastases includes: (i) locally resectable prostate cancer (evaluated on mpMRI), (ii) ≤3 hot spots on bone scan, (iii) pelvic lymph node metastases ≤3 cm, (iv) no retroperitoneal lymph node metastases, and (v) no visceral metastases. Treatment design should include neoadjuvant ADT for 6 months, leading to a decrease in PSA <0.4 ng/mL, followed by extended radical prostatectomy and extended pelvic lymphadenectomy, as well as 2 years of adjuvant ADT. The conclusion of Dr. Heidenreich’s study is that “cytoreductive radical prostatectomy may improve overall and cancer specific survival in a well selected cohort of patients based on the individual PSA response to neoadjuvant ADT. Cytoreductive prostatectomy effectively prevents complications of the lower and upper urinary tract.” 

(iii) Metastasis-Directed Therapy

Dr. Brausi briefly notes that there are a number of metastatic-directed therapy clinical trials for oligometastatic lesions, as well as several retrospective-series that include varying doses and schedules of targeted radiotherapy. 

Dr. Brausi concluded his presentation by noting several important take-home messages: (i) oligometastatic prostate cancer includes a spectrum of biologies and may include a distinct entity that progresses slowly, (ii) local therapy to the prostate appears safe and reduces the need for palliative treatment, as well as radical prostatectomy significantly improving survival compared to ADT alone in lymph node metastases, (iii) cytoreductive radical prostatectomy may be an option in men with good prognosis following neoadjuvant ADT, and (iv) aggressive treatment of oligometastatic prostate cancer should be considered only in the setting of prospective trials.

Speaker: Maurizio Brausi, Ospedale Civile Ramazzini, Carpi, Italy 

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre @zklaassen_md at the EAU - Update on Prostate Cancer  – September 15-16, 2017, Vienna, Austria

References:

1. Gravis G, Boher JM, Joly F, et al. Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial. Eur Urol. 2016;70(2):256-262.
2. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.
3. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163-1177.
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8. Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol 2014;65(6):1058-1066.
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