Abiraterone acetate rechallenge for mCRPC patients with AR mutant / 中华泌尿外科杂志

ABSTRACT

A 75-year-old patient was admitted with "progressive dysuria for more than 2 months" in January 2017. The tPSA level was 498 ng/ml and then diagnosed as metastatic prostate cancer (cT 3bN xM 1). For the resistance of abiraterone, gene mutation was detected during the endocrine therapy. After 5 months of endocrine therapy, the serum tPSA was decreased to a minimum of 12.5 ng/ml. Since July, the serum PSA level gradually rebounded, and the endocrine therapy was altered to androgen deprivation therapy (ADT). The level of tPSA was maintained at 104 ng/ml in October 2017, and ADT was discontinued. After 1 year of discontinuation, the re-examination of PSA was 3 205 ng/ml. As the first-line regimen for mCRPC, abiratone and prednisone combined with goserelin was used. After 5 months of treatment, the level of tPSA still showed progression. The drug resistance of abiraterone was considered, so the treatment was discontinued. Next-generation sequencing technology (NGS) revealed the presence of AR, FGFR3 and RIT1 mutations, while no HRR germline mutation was detected. Docetaxel combined with ADT was performed. It was changed to comprehensive treatment of goserelin + docetaxel in March 2019. During chemotherapy CT images indicated significant reduction of pelvic lymph nodes and left inguinal lymph nodes, while bone metastasis showed stable condition. In April 2020, the chemotherapy was terminated for the lower extremity edema, joint pain and other related discomfort. The level of tPSA was 289 ng/ml after the last chemotherapy. DNA sequencing testing were performed again, and the mutation of AR and AR-V7 was negative. According to the results of genetic testing, the tPSA continued to decrease to 23 ng/ml after 6 months of abiraterone rechallenge, the imagings suggested that no disease progression. After AR mutation turns negative after chemotherapy, patients with refractory CRPC can still obtain a good PSA response such as tumor control and other clinical benefits from abiraterone. Abiraterone rechallenge is probably a new attempt for AR mutant patients with refractory CRPC.