Visceral metastases in castration resistant prostate cancer: Does ¹⁷⁷Lu-PSMA help?

Objectives: The presence of visceral metastases has been linked to poor prognosis in patients of metastatic castration resistant prostate cancer (mCRPC). A recent systematic review and meta-analysis reported that the presence of visceral metastases was associated with poor response and survival outcomes in patients of CRPC treated with ¹⁷⁷Lu-PSMA radioligand therapy (RLT). In this study, we report our institutional experience with ¹⁷⁷Lu-PSMA-617 in patients of CRPC with visceral metastases.

Methods: This was a retrospective, single centre study. Data of consecutive patients of CRPC with documented visceral metastases and treated with ¹⁷⁷Lu-PSMA-617 at our centre, from October 2015 to October 2020, were collected and analysed. The patients were assessed for best PSA response (defined as proportion of patients achieving a ≥50% decline in PSA from baseline), radiological response, progression-free survival (PFS) and safety profile.

Results: Eleven males (median age: 71 years, range: 60-85years) with mCRPC and documented visceral metastases on ⁶⁸Ga-PSMA-11 PET/CT showing tracer uptake greater than that of normal liver were included in this analysis. Of these, liver, lung and adrenal metastases were observed in 7/11 (64%), 2/11 (18%) and 3/11 (27%) patients respectively. Additionally, all the eleven patients had tracer avid skeletal lesions. Prior treatments included: Docetaxel (5 patients); Abiraterone (7 patients) and Enzalutamide (5 patients). The patients received a median cumulative activity of 13.3 GBq (range: 5.9 - 22.2 GBq) of ¹⁷⁷Lu-PSMA-617 over 1-4 cycles at 8-12 weeks intervals. Best PSA response was achieved in 3/11 (27%) patients. Radiological response could be evaluated in 8 patients, of which, only one patient showed a partial response. The median PFS was 3.5 months (95% confidence intervals, 3.0 - 4.5 months). No major grade 3/4 adverse events were noted.

Conclusions: ¹⁷⁷Lu-PSMA RLT has limited efficacy in the treatment of CRPC with visceral metastases. The poor response could be attributed to the neuroendocrine transdifferentiation in such lesions, leading to reduction or loss of PSMA expression. Using a stricter eligibility criterion for patient selection (i.e. treating lesions with PSMA expression 1.5-2 times that of normal liver), as well as dual ⁶⁸Ga-PSMA/ ¹⁸F-FDG PET/CT could possibly lead to better outcomes.