A Pilot Study of a Multimodal Treatment Paradigm to Accelerate Drug Evaluations in Early-stage Metastatic Prostate Cancer

Abstract

OBJECTIVE To evaluate a multimodal strategy aimed at treating all sites of disease that provides a rapid readout of success or failure in men presenting with non-castrate metastatic prostate cancers that are incurable with single modality therapy. MATERIALS AND METHODS Twenty selected men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated using a multimodal approach that included androgen deprivation, radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease or the primary site. Outcomes of each treatment were assessed sequentially. Androgen deprivation was discontinued in responding patients. The primary end point was an undetectable prostate-specific antigen (PSA) after testosterone recovery. The goal was to eliminate all detectable disease. RESULTS Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after androgen deprivation alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval: 3%–38%) achieved the primary end point, which persisted for 5, 6, 27+, and 46+ months. All patients meeting the primary end point had been classified with M1b disease at presentation. CONCLUSION A sequentially applied multimodal treatment strategy can eliminate detectable disease in selected patients with metastatic spread at diagnosis. The end point of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states and to shift the paradigm from palliation to cure.

Initial risk stratification and staging in prostate cancer with prostatic-specific membrane antigen positron emission tomography/computed tomography: A first-stop-shop

“…Extrapelvic lymph node metastasis is another important factor in decision-making; however, its presence is commonly underestimated with conventional staging methods. [ 32 33 34 35 ] In our study, we found that 17.31% of patients had retroperitoneal lymph node metastasis without evidence of hematogenous spread (M 1a ). In addition, PSMA PET-CT showed incremental value in the detection of inguinal and mediastinal lymph node metastasis, contrasting it from conventional methods.…”

Treatment of Advanced Prostate Cancer

“…Recent results have encouraged exploration of a multimodal strategy in oligometastatic advanced prostate cancer, especially because studies suggest that each modality contributes to further disease debulking and, thus, disease control (87). Several studies are evaluating this strategy, including PEACE1 (NCT01957436), MetaCure (NCT03436654), and the radiotherapy arm of MRC STAMPEDE.…”

<p>Oncological Outcome of Combining Cytoreductive Prostatectomy and Metastasis-Directed Radiotherapy in Patients with Prostate Cancer and Bone Oligometastases: A Retrospective Cohort Study</p>

“…These results are in line with the data reported by the most recent literature. 13 , 14 We suggest that cytoreductive RP in combination with metastasis-directed SBRT is a feasible cytoreductive treatment strategy and has the potential to postpone disease progression to CRPC in PCa patients with synchronous bone oligometastases.…”