Key points are not available for this paper at this time.
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. 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 administration, although a grade 2 skin rash was observed in two patients. No other NCHT-related adverse events or perioperative complications were observed. Considering the adverse effects of long-term ADT, it is important to ensure a treatment-free period for patients with mCSPC. Therefore, we suggest that combining NCHT and cRARP may be a helpful treatment modality, potentially offering patients with oligo-PCa a treatment-free period. Moreover, we believe that this treatment may improve OS in the future because of the remarkable decrease in PSA levels, shrinkage of the primary tumor, absence of new metastatic lesions, and a treatment-free period of ≥10 months. Although the number of patients eligible for enrolment was insufficient and the observation period was short, we plan to increase the number of cases and extend the observation period for a comprehensive report. Makoto Kawase: Conceptualization; methodology; data curation; investigation; writing—original draft. Daiki Kato: Data curation. Yuki Tobisawa: Data curation; investigation. Koji Iinuma: Data curation. Keita Nakane: Data curation. Takuya Koie: Conceptualization; methodology; writing—review & editing. None of the authors have conflicts of interest to disclose. Approval of the research protocol by an Institutional Reviewer Board of Gifu University: 2020–115. This study obtained consent for all enrolled patients. The details of this study can be found at UMIN000046528. Not applicable. Not applicable.
Kawase et al. (Thu,) studied this question.