Abstract
PurposeHematotoxicity is a potentially dose-limiting adverse event in patients with metastasized castration-resistant prostate cancer (mCRPC) undergoing prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT). We aimed to identify clinical or PSMA-targeted imaging-derived parameters to predict hematological adverse events at early and late stages in the treatment course.MethodsIn 67 patients with mCRPC scheduled for 177Lu-PSMA-617 RLT, pretherapeutic osseous tumor volume (TV) from 68Ga-PSMA-11 PET/CT and laboratory values were assessed. We then tested the predictive capability of these parameters for early and late hematotoxicity (according to CTCAE vers. 5.0) after one cycle of RLT and in a subgroup of 32/67 (47.8%) patients after four cycles of RLT.ResultsAfter one cycle, 10/67 (14.9%) patients developed leukocytopenia (lymphocytopenia, 39/67 [58.2%]; thrombocytopenia, 17/67 [25.4%]). A cut-off of 5.6 × 103/mm3 for baseline leukocytes was defined by receiver operating characteristics (ROC) and separated between patients with and without leukocytopenia (P < 0.001). Baseline leukocyte count emerged as a stronger predictive factor in multivariate analysis (hazard ratio [HR], 33.94, P = 0.001) relative to osseous TV (HR, 14.24, P = 0.01). After four cycles, 4/32 (12.5%) developed leukocytopenia and the pretherapeutic leukocyte cut-off (HR, 9.97, P = 0.082) tended to predict leukocytopenia better than TV (HR, 8.37, P = 0.109). In addition, a cut-off of 1.33 × 103/mm3 for baseline lymphocytes separated between patients with and without lymphocytopenia (P < 0.001), which was corroborated in multivariate analysis (HR, 21.39, P < 0.001 vs. TV, HR, 4.57, P = 0.03). After four cycles, 19/32 (59.4%) developed lymphocytopenia and the pretherapeutic cut-off for lymphocytes (HR, 46.76, P = 0.007) also demonstrated superior predictive performance for late lymphocytopenia (TV, HR, 5.15, P = 0.167). Moreover, a cut-off of 206 × 103/mm3 for baseline platelets separated between patients with and without thrombocytopenia (P < 0.001) and also demonstrated superior predictive capability in multivariate analysis (HR, 115.02, P < 0.001 vs.TV, HR, 12.75, P = 0.025). After four cycles, 9/32 (28.1%) developed thrombocytopenia and the pretherapeutic cut-off for platelets (HR, 5.44, P = 0.048) was also superior for the occurrence of late thrombocytopenia (TV, HR, 1.44, P = 0.7).ConclusionsPretherapeutic leukocyte, lymphocyte, and platelet levels themselves are strong predictors for early and late hematotoxicity under PSMA-directed RLT, and are better suited than PET-based osseous TV for this purpose.
Highlights
As a type-2 transmembrane protein overexpressed on the surface of prostate and prostate cancer cells, the prostate-specific membrane antigen (PSMA) has emerged as a promising imaging target for men afflicted with prostate cancer (PC) [1, 2]
After one cycle of radioligand therapy (RLT), leukocyte count declined from 7.13 ± 2.36 to 5.82 ± 2.17 × 103/mm3 (P < 0.001); 10/67 (14.9%) patients developed leukocytopenia according to Common Terminology Criteria for Adverse Events (CTCAE)
In receiver operating characteristics (Fig. 1a, b), baseline leukocytes demonstrated the highest accuracy in identifying subjects with and without leukocytopenia with an AUC of 0.87 (P < 0.001, best threshold, 5.6 × 103/mm3), followed by osseous tumor volume (TV) (AUC 0.75, P = 0.002, best threshold, 100cm3) and PSA (AUC 0.71, P = 0.02, best threshold, 260 μg/l)
Summary
As a type-2 transmembrane protein overexpressed on the surface of prostate and prostate cancer cells, the prostate-specific membrane antigen (PSMA) has emerged as a promising imaging target for men afflicted with prostate cancer (PC) [1, 2]. PSMA-targeted positron emission tomography (PET)/ computed tomography (CT) has witnessed expanded use, mainly due to its strikingly higher accuracy in detecting sites. Retrospective studies investigating PSMA-targeted RLT demonstrated high efficacy, even in patients with widespread metastatic disease [8]. The first prospective phase 2 study (LuPSMA trial) further corroborated these findings yielding a PSA decline of >50% in 57% of the enrolled subjects [9]. Further building on these encouraging results, the prospective VISION phase-3 trial will further elucidate the clinical value of PSMA RLT in metastasized castrationresistant prostate cancer (mCRPC) [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
