Efficacy and safety of combination neoadjuvant chemo‐hormonal therapy and robot‐assisted radical prostatectomy for oligometastatic prostate cancer

摘要

Previously, most patients with metastatic castration-sensitive prostate cancer (mCSPC) received hormone therapy, including androgen deprivation therapy (ADT). In a retrospective study using the Surveillance Epidemiology and End Results database, patients with mCSPC and oligometastases (Oligo-PCa) who underwent radical prostatectomy (RP) or brachytherapy experienced prolonged overall survival (OS) compared with those receiving ADT alone.1 Recently, several clinical trials revealed that cytoreductive robot-assisted RP (cRARP) may reduce the risk of radiographic progression or death in patients with Oligo-PCa.2, 3 Additionally, combination therapy with androgen receptor signaling inhibitor (ARSI) and ADT before cRARP has been reported to enhance OS, metastasis-free survival, and quality of life in patients with mCSPC.4, 5 Therefore, neoadjuvant therapy, including ARSI with cRARP, may improve oncological outcomes in patients with Oligo-PCa. Tegafur-uracil (UFT) is a cytotoxic agent that inhibits deoxyribonucleic acid (DNA) repair, and its efficacy has been reported in several clinical studies on castration-resistant prostate cancer.6 Additionally, apalutamide directly binds to the ligand-binding domain of the androgen receptor and acts to inhibit androgen receptor rearrangement, DNA binding, and androgen receptor-mediated transcription.7 In this study, we aim to report our initial experience with the combination of neoadjuvant chemo-hormonal therapy (NCHT) with cRARP for Oligo-PCa. We are conducting a single-arm prospective study of combined NCHT and cRARP for Oligo-PCa. Oligo-PCa was defined as having ≤3 metastatic sites and no visceral metastases. In our protocol, we enrolled 15 patients with Oligo-PCa receiving the combination of a gonadotropin hormone-releasing hormone antagonist, UFT (300 mg daily oral), and apalutamide (240 mg daily oral) for ≥4 months. All patients underwent imaging studies, including magnetic resonance imaging (MRI). Patients with prostate-specific antigen (PSA) levels <0.2 ng/mL and imaging studies indicating no progression underwent cRARP. After cRARP, all treatments were discontinued; however, adding metastasis-directed therapy was considered if PSA reduction was inadequate or pain due to metastasis was present. The primary end point of this study was treatment-free survival (TFS) after cRARP. The patients had their serum PSA and testosterone levels measured every 3 months to assess biochemical recurrence (BCR). Furthermore, imaging studies were carried out every 6 months to assess radiographic progression. BCR was diagnosed when the postoperative serum PSA levels rose to >0.2 ng/mL. JMP Pro 16 (SAS Institute Inc, Cary, NC, USA) was used for data analyses. TFS was analyzed using the Kaplan–Meier method. Fifteen patients were enrolled in the study, and 11 underwent cRARP until 2023. The remaining four patients refused cRARP, three of whom continued hormone therapy and one underwent radiotherapy. Figure 1a shows the characteristics and early oncological outcomes of the patients undergoing cRARP. The median follow-up duration was 27 months. PSA reduction was observed in all patients who underwent cRARP, and pathologically complete response (CR) was observed in two patients. Figure 1b shows the progress of Case 9, where MRI 6 months after NCHT showed remarkable shrinkage of the primary lesion compared to its size before treatment. Histopathological findings of the surgical specimen showed that nearly all cancer cells had disappeared (yellow line) and hyaline deposition had occurred; however, a small number of cancer cells remained in the seminal vesicle (Figure 1c). Although BCR was seen in four cases, no new metastasis to other organs or lymph nodes was observed. The median TFS was 10 months. Furthermore, the 1-year TFS (Figure 1d) and radiographic progression-free survival rates were 68.6% and 100%, respectively. Regarding safety of NCHT, the rash resolved mildly after the discontinuation of apalutamide a