Our study, "Multi-institutional Analysis of Metastasis-directed Therapy with or Without Androgen Deprivation Therapy in Oligometastatic Castration-sensitive Prostate Cancer," endeavors to elucidate the optimal manner of integrating MDT with ADT. Through a multicenter international retrospective cohort analysis, we aimed to shed light on the long-term outcomes of combining ADT with MDT vs MDT monotherapy in patients with conventional imaging detected omCSPC.
The cohort comprised 263 patients, segmented into two groups: those receiving MDT in conjunction with a defined/limited course of ADT (105 patients) and those treated with MDT alone (158 patients). The primary focus was to assess outcomes in terms of biochemical progression-free survival (bPFS), distant progression-free survival (dPFS), and combined biochemical or distant progression-free survival (cPFS). Clinical outcomes were assessed using Kaplan-Meier survival analysis and multivariable Cox proportional hazard regression models for analysis.
A total of 263 patients treated between 2003 and 2018 were included with a median follow-up of 52 months. Patients treated with concurrent ADT were more likely to have synchronous metastatic disease (23% vs 1%, p < 0.001) and less likely to have lymph node–only disease (10% vs 41%, p < 0.001). The median length of ADT prescription was 21.3 months. Patients treated with concurrent MDT + ADT demonstrated significantly improved 5-yr bPFS (24% vs 11%), dPFS (41% vs 29%), and cPFS (19% vs 9%) compared with those treated with MDT alone. On multivariable Cox regression accounting for pre-MDT variables only, concurrent ADT was associated with significantly improved bPFS (hazard ratio [HR] 0.43, 95% CI 0.28–0.67; p < 0.001), dPFS (HR 0.45, 95% CI 0.27–0.76; p = 0.002), and cPFS (HR 0.44, 95% CI 0.28–0.67; p < 0.001).
Given that testosterone suppression would inherently bias the results in favor of the ADT + MDT treatment, we performed an a priori subset analysis of eugonadal PFS evaluating the time to first progression (biochemical or distant) from the time of testosterone ≥150 ng/dl for patients receiving ADT and from the end of MDT for patients not receiving ADT. Testosterone recovery was documented in 44 of the patients who received MDT plus ADT. Within this subset analysis, the use of ADT was still associated with a longer median eugonadal PFS of 21.4 mo (95% CI 2.9–39.9 [HR 0.67, 95% CI 0.44–1.0]) versus 10.2 months (95% CI 8.0–12.5 [HR 0.37, 95% CI 0.24–0.55]). One concern is rate of testosterone recovery and the database recorded the following. By 48 mo after MDT, confirmed testosterone recovery to >150 ng/dl was achieved in 46.2%, 55.8%, and 21.2% of patients receiving ADT for 6, 6–24, and >24 mo of ADT, respectively. Due to limited testosterone testing or reporting, 48-mo testosterone recovery was unknown in 53.8%, 25.0%, and 51.5% of patients receiving 6, 6–24, and >24 mo of ADT, respectively. Some of these men would have had testosterone recovery but are not included in the eugonadal analysis.
This comprehensive multi-institutional report underscores the potential benefits of augmenting MDT with ADT in the management of omCSPC. While approximately 10% of patients demonstrated durable control with MDT alone, the addition of ADT appears to significantly prolong the time to progression and distant recurrence. These findings advocate for a more integrated approach to omCSPC treatment, potentially incorporating concurrent ADT to achieve optimal patient outcomes. It is important to consider that these results specifically evaluate patients with omCSPC detectable on conventional (CT and NM bone scan) imaging. These findings, therefore, may not be applicable in a cohort of PSMA-PET detected omCSPC as it represents an earlier stage in the progression and is believed to represent a more indolent disease
In conclusion, our study contributes valuable insights into the management of omCSPC, advocating for the consideration of combined MDT and ADT as a potentially superior treatment strategy. As the field moves forward, ongoing phase 3 studies are expected to provide further clarity, refining treatment options for omCSPC and paving the way for more effective and personalized therapeutic approaches.
Written by: Matthew P. Deek, MD1 Philip Sutera, MD2 & Christopher Sweeney, MD3
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia.