Case Report: Two cases of chemotherapy refractory aggressive variant prostate cancer with extreme durable response to PARP inhibitor

Abstract

Background: Aggressive variant prostate cancer (AVPC) represents a distinct clinical subset characterized by resistance to novel hormone therapies and an unfavorable prognosis, frequently associated with the concurrent loss of tumor suppressor genes (TSG) such as PTEN, RB1, and TP53. While the progression-free survival (PFS) and overall survival (OS) of AVPC are relatively short, the optimal first-line treatment remains unclear.

Presentation: In this case report, we presented two de novo AVPC cases who have ultimately benefited from the usage of PARP inhibitors. The first patient was a 64-year-old male who was diagnosed during prostate biopsy featured by mutations in PTEN, and loss of RB1, BRCA2, ATM, and FANCA. He was treated with docetaxel/albumin-bound paclitaxel and cisplatin in the first line. Second-line therapy was applied with radiotherapy and Olaparib after failure of first-line therapy, resulting in a PSA response sustained for three years. The second case was a 75-year-old male with localized neuroendocrine feature and mutations in TP53, loss of RB1 and HDAC2. He was treated with sustained ADT and chemotherapy in the first-line treatment. Radiotherapy and Fluzoparib + abiraterone was applied as subsequent treatments with a PSA response for 2 years.

Conclusions: These two cases demonstrating a satisfactorily durable response to PARP inhibitors indicating its clinical benefit in AVPC population with detected DNA damage response (DDR) defects. The survival improvement with PARP inhibitors observed in our clinical experiences, along with current advances in tumor sequencing provide more information on future clinical trials and explorations of innovative therapies in AVPC population.

Keywords: PARP inhibitor; aggressive variant prostate cancer; chemotherapy; prostate cancer; radiotherapy; treatment.

Figure 1

Serum PSA level (A) and ECT results (B–D) of case 1. (A). LHRH: Luteinizing Hormone-Releasing Hormone. Chemotherapy: docetaxel/albumin-bound paclitaxel + cisplatin. The detailed dates and values of each PSA test can be found in the Supplementary Table S2 ; (B) ECT results for April 2021, radionuclide-concentrating foci were seen in T2-T3 vertebrae, right 12^th posterior rib, L5 vertebrae and bilateral iliac bones; (C, D). The ECT results from November 2021 and November 2022 revealed no newly developed bone metastases.

Figure 2

The trend of changes in various blood indicators during the entire treatment process of case 1 (A) and case 2 (B). (1) Units for blood indicators: Granulocyte, Leukocyte, Lymphocyte, Platelet: 10⁹/L; Red blood cell (RBC): 10¹²/L; Hemoglobin: g/L. (2) In order to display the two indicators of hemoglobin and platelets on the same figure with the other four indicators, all hemoglobin values were divided by 15 and all platelet values were divided by 20.

Figure 3

Serum PSA level (A) and ECT results (B–E) of case 2. (A). LHRH: Luteinizing Hormone-Releasing Hormone. Chemotherapy: docetaxel/albumin-bound paclitaxel + cisplatin. Detailed dates and values of each PSA test can be found in the Supplementary Table S3 ; (B) (December 2020, at the time of diagnosis) Multiple radionuclide-concentrating foci were seen in bilateral ribs, L1 vertebrae, left femur, right iliac bone, pubic symphysis and right wrist; (C) (April 2022, before radiotherapy) Radionuclide-concentrating foci were detected in bilateral ribs, L1 vertebrae and right wrist. (D) (October 2022, before treatment of Fluzoparib) Radionuclide-concentrating foci of bilateral ribs and T2-T4、L1 vertebrae; (E) (April 2023, after 6-month treatment of Fluzoparib) A reduction of metastatic foci on bilateral ribs and vertebrae was seen.