Overall survival of prostate cancer patients treated with Lu‑177 PSMA 617 (Pluvicto®) in a multidisciplinary setting— a single center experience

Rákkutatás · Prostate cancer

The multidisciplinary approach can positively influence overall survival of metastatic castration‑resistant prostate cancer patients treated with Lu‑177 PSMA‑617.

Introduction: VISION trial led to the approval of Lu-177 PSMA-617 for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have received at least one androgen receptor pathway inhibitor and one taxane based chemotherapy. Since its approval, nomograms and other predictive and prognostic markers have been proposed for patient selection, as not all patients respond to Lu-177 PSMA. We retrospectively evaluated the impact of multidisciplinary approach on overall survival (OS) of mCRPC patients referred for Lu-177 PSMA therapy in our center and compared it with the historical OS and PSA response data from the VISION and TheraP trials. In VISION trial, patients were selected based on PSMA PET only whereas in TheraP trial dual PET i.e. PSMA and FDG PET were used for patient selection. Methods: After IRB approval, patient’s electronic records were retrospectively reviewed and data collected in an institutional database. All patients were discussed in our multidisciplinary theranostics tumor board (TTB). All patients deemed eligible for treatment with Lu-177 PSMA were screened with PSMA PET/CT (no FDG PET). Wherever feasible, patients underwent post-therapy PSMA SPECT/CT after every cycle. TTB recommended continuation or discontinuation of therapy after assessing laboratory values, post-therapy SPECT/CT and ECOG status of patients. For this study, the following data were analyzed: age, time of first cycle, time since first diagnosis, time since PSMA PET, interval from first treatment to last follow-up (FU) PSA at baseline, PSA after 2nd cycle, PSA after the last cycle, PSA response defined as PSA50 i.e. > 50% drop in PSA at the end of last cycle and after 2nd cycle, number of cycles, dose modification (if any), survival status, date of last follow-up. All statistical analyses were performed in SPSS v30. p-value < 0.05 was considered as statistically significant. VISION and TheraP trial OS of 15.3 months 19.1 months were benchmarks. Results: Out of 114 patients discussed in TTB, 90 patients (mean age of 71.4 ± 8.0 years) were found to be eligible to receive Lu-177 PSMA, 8 were enrolled in clinical trials and 16 were ineligible. 60.8% of the patients received ≥5 cycles of therapy whereas 19.5% were treated with ≥2 at the time of data analyses. TTB recommended dose modification in 14.4% of patients. PSA50 response was observed in 41.4% and 43.2% (vs. 46% in VISION trial) after the 2nd and last cycles, respectively. Median follow-up duration was 13.5 months. Thirty-three (36.7%) died during follow-up. Median OS was found to be 19.1 months (95% CI 15.7-22.5, figure 1). Patients treated with ≥5 cycles (median not reached) had significantly higher OS as compared to those with ≤ 4 cycles (5.9 months; log rank test p <0.001). Patient achieving PSA50 response after last cycle had significantly higher OS compared to those that did not (median not reached vs 17.5 months; log rank p=0.006). Patients not showing PSA50 after 2 cycles were found to have lower OS (median not reached vs. 19.1 months; log rank p=0.031, figure 2). In a multivariate analysis consisting of PSA50 after the 2nd cycle, after last cycle and number of cycles, only the latter (≥5 cycles) was found to be an independent predictor of OS. Conclusions: Within the limitations of comparing real world data with multicenter prospective trial data, in our single center experience, median overall survival was found to be approximately 4 months higher than OS reported in VISION trial and equal to that in TheraP trial. The multidisciplinary approach, integrating clinical performance, laboratory values and post-therapy SPECT/CTs can positively influence the overall survival of mCRPC patients treated with Lu-177 PSMA.

This study demonstrates that incorporating multidisciplinary assessment—clinical status, laboratory data, and post‑therapy imaging—improves overall survival in metastatic castration‑resistant prostate cancer patients receiving Lu‑177 PSMA‑617. The findings support the use of a tumour board approach to optimise patient selection and treatment planning, which could lead to better outcomes in routine practice.

Bizonyítékszint: Állatkísérletes. Állatmodellben vizsgálták.

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