Introduction:
Sipuleucel-T (Sip-T) has been shown to improve the overall survival in patients with metastatic castrate-resistant prostate cancer (mCRPC). Recently, studies have shown potential benefit of lymph node dissection (LND) for lymph-node predominant, oligometastatic prostate cancer. With IRB approval, this phase 1, randomized trial evaluated the effect of LND on mCRPC patients with pelvic, retroperitoneal, or inguinal lymph node predominant disease around the time of treatment with Sip-T (ClinicalTrials.gov: NCT02036918).
Methods:
Patients were randomized 1:3 between LND followed by Sip-T (Arm A) and immediate Sip-T followed by LND (Arm B). Follow up for 6 months after treatment included PSA assessment and restaging imaging. We evaluated clinical parameters of recurrence based on the Prostate Cancer Working Group 2 and RECIST 1.1 definitions, with specific designation of surgical-field lymph nodes as non-target lymph nodes to avoid false characterization of post-LND resolution of radiographic disease as a complete remission. Progression-free survival (PFS), overall survival (OS), and freedom from next line of therapy were evaluated between arms (intention-to-treat) and as a function of clinical parameters using R version 3.6.3.
Results:
20 patients (arm A=5, arm B=15) were included in our analysis. Demographics, baseline characteristics, and treatment results are presented in Table 1. Most patients underwent open LND of pelvic or retroperitoneal disease. Ability to achieve a complete resection differed between the two arms, due to severe fibrosis from prior treatment or extra-template disease. PSA responses of the participants are highlighted in Figure 1, demonstrating typically longer time to progression in Arm A. OS and PFS were not statistically different between the two arms. However, patients who underwent complete resection of disease were found to have improved survival metrics compared to those who had incomplete resection. Pre-study PSA doubling time < 3 months was associated with worse PFS (median 2.5 months vs 6 months, p = 0.0054). Only baseline PSA doubling time was associated with a significant difference in median time to next line of therapy.
Conclusion:
LND around the time of Sip-T treatment of mCRPC may have favorable effects on disease response in select patients with long baseline PSA doubling time and ability to undergo complete resection. Further study of the immune signatures of these phenomena will allow better understanding of the applicability of extirpation in metastatic prostate cancer, as well as the predictors of favorable response to Sip-T in lymph node predominant mCRPC.
Funding: Dendreon
Image(s) (click to enlarge):
IMPACT OF LYMPHADENECTOMY ON THE RESPONSE TO SIPULEUCEL-T TREATMENT OF METASTATIC CASTRATE-RESISTANT PROSTATE CANCER
Category
Prostate Cancer > CRPC
Description
Poster #135
-
Presented By: Ankeet Shah
Authors:
Ankeet Shah
Dominic C. Grimberg
Scott P. Campbell
Rohith Arcot
Wiguins Etienne
Brant A. Inman