Personalized downstaging treatment with ADT, chemotherapy and add-on zimberelimab for very-high-risk clinically localized prostate cancer: A case report.

Rationale: Very-high-risk prostate cancer (PCa) is associated with poor prognosis. Radical prostatectomy (RP) is an option for selected high-risk PCa cases, especially in younger, healthier patients. However, a high Gleason score and high T stage can increase the risk of RP. Neoadjuvant therapy has been reported in high- or very-high-risk PCa, but its clinical use remains controversial.

Diagnoses And Patient Concerns: A 53-year-old male patient diagnosed with PCa was referred to our hospital. The patient's Gleason score was 4 + 5, and the clinical stage was T4N0M0, with an abnormally enlarged prostate adhering to the rectum and leading to decreased mobility of the rectum, suggesting a very-high-risk PCa inappropriate for RP. However, instead of external beam radiation therapy, which is the standard treatment for inoperable PCa, the patient insisted on RP.

Interventions: Androgen deprivation therapy plus docetaxel was chosen as the first downstaging treatment; however, the tumor was too slightly downsized to undergo RP. Therefore, zimberelimab was added after confirmation of a genomic feature of high microsatellite instability and high tumor mutational burden status.

Outcomes: After 4 doses of zimberelimab, the prostate shrank significantly. The patient successfully completed RP after another dose of zimberelimab, and achieved a pathological complete response (pCR).

Lessons: Our case represents a successful attempt at personalized treatment and provides preliminary evidence for the clinical use of downstaging therapy of androgen deprivation therapy, chemotherapy, and add-on zimberelimab for very-high-risk clinically localized PCa.