RESUMO
Lutetium-177 prostate-specific membrane antigen radioligands (177Lu-PSMA) are new therapeutic agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We evaluated the prognostic value of circulating tumour DNA (ctDNA) profiling in patients with mCRPC starting treatment with 177Lu-PSMA I&T. Between January 2020 and October 2022, patients with late-stage mCRPC (n = 57) were enrolled in a single-centre observational cohort study. Genomic alterations in the AR gene, PI3K signalling pathway, TP53, and TMPRSS2-ERG were associated with progression-free survival (PFS) on Kaplan-Meier and multivariable Cox regression analyses. Median PFS of 3.84 mo (95% confidence interval [CI] 3.3-5.4) was observed, and 21/56 (37.5%) evaluable patients experienced a prostate-specific antigen response of ≥50% during treatment. Among 46 patients who provided a blood sample for profiling before 177Lu-PSMA treatment. ctDNA was detected in 39 (84.8%); higher ctDNA was correlated with shorter PFS. Genomic structural rearrangements in the AR gene (hazard ratio [HR] 9.74, 95% confidence interval [CI] 2.4-39.5; p = 0.001) and alterations in the PI3K signalling pathway (HR 3.58, 95% CI 1.41-9.08; p = 0.007) were independently associated with poor 177Lu-PSMA prognosis on multivariable Cox regression. Prospective evaluation of these associations in biomarker-driven trials is warranted. Patient summary: We examined cell-free DNA in blood samples from patients with advanced metastatic prostate cancer who started treatment with lutetium-177-PSMA, a new radioligand therapy. We found that patients with genetic alterations in the androgen receptor gene or PI3K pathway genes did not experience a lasting benefit from lutetium-177-PSMA.
RESUMO
BACKGROUND: Small cell carcinoma of the prostate is a rare condition with important differences from prostatic adenocarcinoma in terms of clinical and prognostic characteristics. A low prostate-specific antigen and a symptomatic patient, including paraneoplastic symptoms, characterize small cell carcinoma of the prostate. Diagnosis is made on the basis of prostate biopsy, and fluorodeoxyglucose positron emission tomography/computed tomography is often used for staging because up to 60% of patients present with de novo metastatic disease. Patients with metastatic disease are usually treated with platinum-based cytotoxic chemotherapy regimens similar to those used for small cell carcinoma of the lung. However, prognosis remains poor, with a median overall survival of 9 to 17 months despite therapy. CASE PRESENTATION: This report describes a case of an 80-year-old Caucasian patient with lymph node and bone metastatic small cell carcinoma of the prostate following low-dose-rate brachytherapy for a low-risk prostate carcinoma and treated with chemotherapy and immunotherapy. CONCLUSION: Low-dose-rate brachytherapy might be an etiology of small cell prostate cancer.