ASCO 2017: Intensification of Therapy for Locally Advanced and Oligometastatic Disease (Discussing Abstract 5018, 5019, 5020)
Dr. Palapattu started his talk by noting that the clinical evolution of prostate cancer over the last several years has resulted in clinicians seeing fewer low-risk and greater high-risk cases, and that there has been an emphasis on risk based treatment allocation secondary to our recognition of disease heterogeneity. Prostate cancer progression is thought to begin in the prostate, then to the regional nodes and finally beyond to the bones and visceral tissue. A subset of these patients will develop oligometastatic disease. As Dr. Palapattu quotes Dr. Willet Whitmore, for these patients “A better outcome may be possible in whom it is necessary.”
There are several unresolved questions when considering treatment of oligometastatic disease: (i) How do we define disease burden? (ii) Which consolidative/site-directed treatment should we choose? (iii) What level of disease burden should we treat? (iv) Which systemic treatments should we choose? (v) How do we sequence treatments? and (vi) What is the appropriate endpoint to select when treating patients in this context?
Discussing the Lestingi et al.1 abstract, Dr. Palapattu starts by congratulating the investigators for performing a “fairly robust surgical clinical trial.” In this study randomizing men to extended pelvic lymph node dissection (ePLND) versus limited pelvic lymph node dissection (lPLND), nearly 2/3 of positive lymph nodes were found outside the obturator chain (62.5%). As the authors conclude, ePLND leads to better staging, increased morbidity, and no oncologic benefits in the initial short follow-up time. Dr. Palapattu notes that in cancer sites where lymphadenectomy has proven to be beneficial, it has always been in concert with a systemic therapy that is also effective.
The Hussain et al.2 abstract assessed adjuvant androgen deprivation therapy with or without mitoxantrone + prednisone for high-risk men undergoing radical prostatectomy. The authors found that both disease free survival (DFS) and overall survival (OS) were similar between the two arms of the trial. Furthermore, in subgroup analyses, including (i) Gleason sum 7 + positive margins or PSA >10 or other risk factors, (ii) Gleason sum ≥8 or T3a/bN0, or (iii) N1 disease, there was no benefit to the mitoxantrone treatment arm. Importantly, this treatment regimen lead to a greater incidence of secondary cancers, namely leukemia. The authors concluded that OS was higher than expected in both arms, mitoxantrone did not improve OS and lead to other malignancies, and the data illustrate the point that systemic therapy benefit in prostate cancer cannot be extrapolated from different disease stages and that there needs to be adequate follow-up in adjuvant prostate cancer trials.
The final abstract was Tran et al.3, assessing the efficacy of stereotactic ablative radiation therapy (SABR) for the treatment of oligometastatic prostate cancer. Oligometastatic disease in this study was defined as up to six osseous, nodal, or visceral metastases, of which 66 men were evaluated. SABR was delivered in 1-5 fractions of 5-18 Gy. Among the 18 men with hormone sensitive prostate cancer who had their ADT deferred, 56% remain free of disease following SABR (1-year ADT-FS of 78%) and in 17 CRPC patients, 11 had > 50% PSA declines with 1-year TTNI of 30% over a median of 45 weeks. The authors concluded that consolidative SABR for oligometastatic disease is feasible and well-tolerated and that SABR delays time to next treatment. More definitive conclusions await the completion of prospective randomized trials, such as the Belgian STOMP and the Baltimore ORIOLE trials.
Dr. Palapattu concluded that there are a number of items we need moving forward with regard to treating oligometastatic disease: (i) more RCTs, (ii) molecular risk stratification, (iii) better systemic treatments, (iv) assessment of immunotherapies, and (v) study endpoint consensus.
Presented By: Ganesh S. Palapattu, MD, University of Michigan, Ann Arbor, MI, USA
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
References:
1. Lestingi JFP, Guclielmetti G, Pontes Jr J, et al. Extended versus limited pelvic lymphadenectomy during radical prostatectomy for intermediate- and high-risk prostate cancer: Early outcomes from a randomized controlled phase III study. J Clin Oncol 2017;35(suppl; abstr 5018).
2. Hussain M, Tangen CM, Thompson IM, et al. Adjuvant androgen deprivation (AD) +/- mitoxantrone + prednisone (MP) in patients with high-risk prostate cancer (PC) post radical prostatectomy (RP): Phase III intergroup trial S9921. J Clin Oncol 2017;35(suppl; abstr 5019).
3. Tran PT, Moyer CL, Phillips R, e al. Stereotactic ablative radiation therapy for the treatment of oligometastatic prostate cancer. J Clin Oncol 2017;35(suppl; abstr 5020).