(UroToday.com) The Society of Urologic Oncology (SUO) annual winter meeting included an advanced prostate cancer session and a presentation by Dr. Brian Chapin discussing the role of surgery and radiation in metastatic prostate cancer. Dr. Chapin emphasized that the rationale for definitive treatment of the primary tumor in metastatic prostate cancer has several bases. This includes (i) retrospective data suggesting an improvement in overall survival, (ii) reduction of local symptomatic progression, (iii) persistence of molecularly “lethal prostate cancer” in the primary tumor, (iv) alteration of tumor biology by systemic therapy, and (v) feasibility and safety of a randomized trial for local therapy.
In 2013, Dr. Chapin and colleagues started a multicenter, randomized, phase II trial of best systemic therapy or best systemic therapy plus definitive treatment of the primary tumor in metastatic prostate cancer. The primary endpoint is CRPC progression and the trial schema for this trial is as follows:
Currently, this trial has completed enrollment and data analysis is underway, of which part of the results were shared by Dr. Chapin at the SUO meeting. There were 60 patients randomized to best systemic therapy and 59 patients randomized to best systemic therapy + local therapy. In both groups, the majority of these patients were M1b (47/60 in best systemic therapy; 42/59 in best systemic therapy + local therapy). In the best systemic therapy + local therapy group, 43 patients underwent radical prostatectomy, and six patients in the best systemic therapy group underwent definitive local therapy after CRPC disease progression.
The overall hypothesis is that there are biologically distinct subsets of prostate cancer with unique therapeutic vulnerabilities. Dr. Chapin notes that among these clinically meaningful subsets of prostate cancer are those that are (i) androgen driven, (ii) undetermined or androgen enabled, and (iii) androgen indifferent. As part of this phase 2 trial are several additional molecular analysis aims:
- Aim 1: Frequency of molecular subsets in primary and metastatic tumors in de novo metastatic disease
- Aim 2: Frequency of molecular subsets in ‘liquid biopsies’ and explore changes as a result of local therapy
- Aim 3: Associations with outcome of molecular subsets and the effect of local therapy
Based on early analysis from the phase 2 trial, Dr. Chapin notes that they have established that the aggressive variant prostate cancer molecular signature is detectable in castration-sensitive prostate cancer diagnostic core biopsies. Additionally, this signature may be prognostic in castration-sensitive disease (although not all data has been analyzed, there is a potential splitting of the Kaplan-Meier curve):
An early look at the safe and toxicity data shows that there have been no grade 4/5 adverse events in either group (and no rectal injuries among patients undergoing radical prostatectomy) with balanced Grade 1-3 toxicities amongst the two groups. Furthermore, EPIC-QoL data is pending final analysis.
For the remainder of his presentation, Dr. Chapin discussed the randomized, phase III trial of standard systemic therapy or standard systemic therapy + definitive treatment of the primary tumor in metastatic prostate cancer (S1802). The trial schema for the phase III trial is as follows:
To date, Dr. Chapin emphasized that there have been several key points regarding the SWOG 1802 trial:
- New sites can still open and enroll patients
- Enrollment can take place anytime up to 28 weeks after starting standard (NCCN) systemic therapy
- Patients must be deemed resectable in order to enroll
- Metastasis-directed therapy is allowed in oligometastatic patients prior to randomization
- The question of benefit of local therapy in the setting of advanced systemic treatment is still unanswered
As follows are the S1802 baseline demographics to date:
Tumor markers will also be assessed in S1802, integrating molecular profiling of circulating tumor cells and matched plasma + radiomic analysis. To date, there are 411 samples among 237 unique patients, with the collection of ~20 samples/month.
Dr. Chapin concluded his presentation with the following take-home messages:
- Cytoreductive surgery should not be offered off trial
- Treatment of the primary tumor in the setting of metastatic disease is likely not beneficial for everyone
- There is a need to understand the biology and mechanism underlying potential benefit in order to (i) intelligently integrate multimodality therapies and (ii) personalize care
Presented by: Brian F. Chapin, MD, Associate Professor of Urology, M.D. Anderson Cancer Center, Houston, TX
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 Society of Urologic Oncology (SUO) Winter Annual Meeting, Orlando, FL, Wed, Dec 1 – Fri, Dec 3, 2021.