Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration-resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with ¹⁷⁷ Lu-prostate-specific membrane antigen (PSMA)-617.

Seventy-one patients with mCRPC were treated with 1 to 5 cycles of ¹⁷⁷ Lu-PSMA-617 (6.0-7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression-free survival (PFS) were analyzed after one, three, and five cycles of RLT.

PSA response rates were not significantly different between patients receiving ¹⁷⁷ Lu-PSMA-617 plus dexamethasone and those receiving ¹⁷⁷ Lu-PSMA-617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (-21% ± 50% vs +11% ± 90%, P = .08; -21% ± 69% vs +22% ± 116%, P = .07; -13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving ¹⁷⁷ Lu-PSMA-617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47-1.61]; P = .20). Multiple regression analysis showed that age (P = .0110), alkaline phosphatase levels (P = .0380) and adjunct dexamethasone (P = .0285) were independent predictors of changes in PSA in patients with bone metastases.

We observed high response rates to ¹⁷⁷ Lu-PSMA-617 RLT in men with mCRPC. The short-term addition of dexamethasone to ¹⁷⁷ Lu-PSMA-617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting.