The value of tumor markers in men with metastatic prostate cancer undergoing [177 Lu]Lu-PSMA therapy.

BACKGROUND: Currently, prostate-specific membrane antigen-radioligand therapy (PSMA-RLT) is considered a last-line treatment option in advanced castration-resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA-RLT and whether the changes assessed after PSMA-RLT correlate with the OS. METHODS: The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro-gastrin-releasing peptide (pro-GRP). For the evaluation, we performed blood tests before each PSMA-RLT cycle and during follow-up visits (which were 2-3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional-hazards regression model. The significance level was set at P < .05. RESULTS: The study included 137 patients who received a total of 487 PSMA-RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut-off), LDH (248 U/L cut-off), and PSA (first quartile cut-off) correlated significantly with survival post-PSMA-RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro-GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS. CONCLUSION: Along with the established tumor marker PSA, ALP, LDH, BAP, and pro-GRP were correlated with the OS post-PSMA-RLT in the univariate and multivariate analyses.

Outcome and safety of rechallenge [177Lu]Lu-PSMA-617 in patients with metastatic prostate cancer.

BACKGROUND: Data are sparse regarding the feasibility of radioligand therapy (RLT) with [177Lu]Lu-PSMA-617 as a retreatment. We aimed to assess the outcome and safety of rechallenge PSMA-RLT in patients with progressive prostatic cancer who previously benefited from this therapy. MATERIALS AND METHODS: Patients who received rechallenge therapy at our department from January 2015 to March 2018 were assessed. Non-haematological and haematological adverse events were evaluated from laboratory data and clinical reports and were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Time to prostate-specific-antigen (PSA) progression and the overall survival (OS) rate of the study patients were calculated from the date of the first rechallenge cycle. Furthermore, the OS calculated from the first cycle baseline PSMA-RLT was compared with the survival of patients who received only baseline PSMA-RLT. The response data were determined using [68Ga]Ga-PSMA-PET/CT and measurements of the tumour marker PSA. RESULTS: Included in this retrospective study were 30 patients who were initially treated with a median of 3 cycles (range 1-5) of PSMA-RLT and were eventually retreated after a median of 6 months (range 2-26). Each patient received a median of 3 (range 1-6) rechallenge cycles. None of the patients experienced a disabling or life-threatening grade 4 adverse event according to the Common Toxicity Criteria (CTC). Grade 3 toxicity occurred in 8 patients (27%). Serious adverse events included leucopoenia (n = 2), neutropoenia (n = 1), anaemia (n = 4), thrombopenia (n = 4) and elevated renal parameters (n = 1). Irreversible adverse events occurred in 21 patients (70%). The permanent adverse events were mild/moderate (CTC grade 1/2) in 19 patients and serious (CTC grade 3) in two patients, respectively. According to PSA measurements, 75-90% of patients showed a benefit (response/stable) from the first 4 rechallenge cycles. The median OS was 12 months calculated from the first rechallenge cycle and 25 months calculated from the first cycle baseline PSMA-RLT. For comparison, the median OS in patients who received only baseline PSMA-RLT was 9 months. The difference according to the logrank test was significant: p value <0.001. Patients with a PSA decrease after the first cycle of rechallenge PSMA-RLT survived a median of 19 months, while patients with a PSA increase survived only 6 months. CONCLUSION: Rechallenge prostate-specific membrane antigen (PSMA) therapy has an acceptable safety profile. The majority of the retreated patients benefited from the rechallenge therapy. Patients who showed a biochemical response achieved a longer OS compared to patients who did not respond. The median OS was significantly longer in patients after rechallenge PSMA-RLT than in patients who received only baseline PSMA-RLT.