高腫瘤突變負荷量作為判斷帕博利珠單抗在轉移性去勢抵抗性前列腺癌療效的預測性生物標誌：病例報告及文獻綜述

郭人豪¹ 許齡內² 蔡欣孜¹ 蔡宗欣² 蔡育賢¹

¹國立成功大學醫學院附設醫院 泌尿部；²安南醫院 泌尿科

High Tumor Mutational Burden as a Predictive Biomarker for Pembrolizumab Efficacy in Metastatic Castration-Resistant Prostate Cancer: A Case Report and Literature Review

Jen-Hao Kuo ¹, Lin-Nei Hsu ², Shin-Tzu Tsai ¹, Tzong-Shin Tzai ², Yuh-Shyan Tsai ¹

Department of Urology¹, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Urology², Annan Hospital, Tainan, Taiwan

Background: Immune checkpoint inhibitors have transformed treatment for several solid tumors, but efficacy in metastatic castration-resistant prostate cancer (mCRPC) remains limited. Genomic alterations, such as high tumor mutational burden (TMB), have emerged as potential biomarkers of response. Although pembrolizumab was FDA-approved for TMB-high solid tumors based on a retrospective analysis, mCRPC was not included, and its clinical effects in these patients require further investigation. This case report describes the use of TMB-based genetic testing to guide pembrolizumab therapy in an mCRPC patient.

Case Description: A 61-year-old man was diagnosed with metastatic castration-resistant prostate cancer (mCRPC), presenting with gross hematuria and a PSA level of 305 ng/mL. Despite receiving androgen deprivation therapy, salvage radiotherapy, chemotherapy, and dendritic cell therapy, his disease continued to progress over the next four years. Owing to progression with significant prostate enlargement (186 ml), he suffered from recurrent gross hematuria and urinary retention, necessitating suprapubic cystostomy. Genetic testing eventually revealed a high tumor mutational burden (TMB), leading to the initiation of pembrolizumab therapy. After three doses, MRI revealed a substantial reduction in prostate size to 90 ml, and his PSA dropped from 180 ng/ml to 0.02 ng/mL. Subsequent palliative and salvage robot-assisted radical prostatectomy was done after the fourth dose. Pathology revealed only minimal residual viable cancer cells. His PSA declined to 0.01 ng/mL and remains at this level. Following a total of nine pembrolizumab doses, he has remained disease-free for over a year with no signs of recurrence. Further genetic analysis at initial diagnosis indicated a sustained high mutation burden (more than 10 mutations per megabase).

Conclusion: This case underscores the utility of TMB-based genetic testing in guiding immunotherapy for advanced prostate cancer. The patient’s response highlights the potential of pembrolizumab in managing TMB-high mCRPC, emphasizing the importance of molecular profiling in treatment planning.