Мутация гена KMT2C предсказывает раннюю резистентность к кастрационной терапии при раке простаты

Alterations in the KMT2C gene in men with prostate cancer may predict early castration resistance, investigators reported in Current Oncology. “KMT2C alteration emerged as the strongest independent genomic predictor of both early castration resistance and overall survival, a finding now supported by mechanistic evidence and corroborated by an independent cohort,” Merve Turan, MD, and Merve Çırak Balta, MD, of Adnan Menderes University, Aydın, Turkey, reported. Their single-center, observational, retrospective Turkish cohort study spanned 2019 to 2025. The study included 92 men (mean age at diagnosis 66.3 years) with androgen pathway modulation-sensitive prostate cancer who underwent next-generation sequencing (NGS)-based analysis of tumor tissue to identify genetic changes potentially predictive of early castration resistance. The study’s primary endpoint was the time to castration-resistant prostate cancer (CRPC) from initiation of androgen-deprivation therapy (ADT). Secondary endpoints included overall survival (OS) from ADT initiation and from date of diagnosis. Overall, 66 patients (71.7%) developed CRPC over a median 21.1 months (interquartile range, 9.3-23.8). The median OS was 36.3 months from ADT initiation and 37.0 months from diagnosis. The most frequently altered genes included ATR in 33 patients (35.9%), PTEN in 26 patients (28.3%), TP53 in 24 patients (26.1%), and BRCA2 in 14 patients (15.2%). KMT2C alterations were found in 5 patients (5.4%). MRE11 alterations were detected in 8.7%. No one had CDK12 alterations. Investigators identified KMT2C alteration as the genomic factor most strongly predictive of shorter time to CRPC (in one model: hazard ratio [HR], 6.804; 95% CI, 1.882-24.601; P =.003). Median times to CRPC were 6.4 months (95% CI, 2.6-10.2 months) for patients with altered KMT2C and 21.3 months (95% CI, 15.6-26.9 months) for patients with wild-type KMT2C (log-rank P =0.023). KMT2C alterations were also associated with shorter OS from the time of ADT initiation (HR, 4.730; P =.019). TP53 alteration also was identified as an independent predictor of shorter OS from the time of ADT initiation (HR, 1.810; P =.038). The researchers tested an exploratory risk scoring system using clinical-genomic variables to stratify patients into 3 prognostic groups. This risk score significantly distinguished outcomes across groups (high vs low risk: HR, 7.904; 95% CI, 2.260-27.644; P =.001). Median times to CRPC were not reached for the low-risk group, 23.7 months for the intermediate-risk group, and 14.3 months for the high-risk group (overall P <.001). The researchers cautioned the score was developed post hoc and should be evaluated prospectively prior to being used in clinical practice. “Taken together, these findings support the routine integration of NGS testing at ADT initiation as both a prognostic tool and a platform for biomarker-guided treatment decisions in prostate cancer,” according to the investigators. This article originally appeared on Renal and Urology News