Editor's Note: While most prostate cancers have a favorable prognosis following radical surgery, once the disease progresses to metastatic castration-resistant prostate cancer (mCRPC), treatment options become limited, with a median survival time of less than three years. In recent years, there have been significant advancements in the field of immunotherapy. However, immunotherapy has not shown significant efficacy in the majority of prostate cancer patients. This study aimed to further analyze the effectiveness of immunotherapy in mCRPC patients by examining tumor mutational burden (TMB). This summary is provided for our readers.This study explored the relationship between tumor mutational burden (TMB) status and the efficacy and prognosis of mCRPC patients treated with the immune checkpoint inhibitor pembrolizumab. The study retrospectively analyzed data from 23 mCRPC patients who received pembrolizumab between 2014 and 2023, all of whom underwent next-generation sequencing (NGS) to determine their TMB status.
The results showed that among the 23 evaluable patients, 10 were classified as having high TMB, while 13 were classified as having low/mid TMB. The overall response rate (ORR) in the high TMB group was 50%, compared to 0% in the low/mid TMB group. Specifically, two patients in the high TMB group achieved complete response (CR), and 50% of patients in this group achieved a prostate-specific antigen (PSA) reduction of over 50% (PSA50), a result not observed in the low/mid TMB group. Additionally, the two patients who achieved CR also saw a PSA reduction of over 90% (PSA90).
Regarding survival outcomes, the progression-free survival (PFS) in the high TMB cohort was significantly longer than in the low/mid TMB cohort, with PFS of 19.34 months versus 2.53 months, respectively. Although overall survival (OS) in the high TMB cohort showed an improving trend, the difference did not reach statistical significance.
Although the proportion of mCRPC patients with high TMB is small, the study’s findings suggest that high TMB status may be associated with better responses to immunotherapy and longer PFS. However, due to the small sample size, the study may be influenced by outliers, particularly the two patients who achieved CR. Therefore, larger prospective studies are needed to further validate these findings.
In summary, this single-center cohort study revealed that higher TMB status in mCRPC patients is associated with clinical responses to immunotherapy and longer PFS, providing valuable insights for future treatment strategies.
