Personalized downstaging treatment with ADT, chemotherapy and add-on zimberelimab for very-high-risk clinically...

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.

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.

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.

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).

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.