For patients with clinically localized prostate cancer and a life expectancy beyond 10 years, radical prostatectomy is the treatment of choice. Recently, more than 80% of radical prostatectomy procedures in the USA are performed with robotic assistance [18]. Recent literature reviews and meta-analyses show that RARP is associated with decreased rates of PSMs, improvements in potency and continence recovery at short-term follow-up, and shorter hospital stay compared to open and laparoscopic radical prostatectomy approaches in low- and intermediate-risk patients [19].
However, 20–30% of patients continue to present with D'Amico high-risk prostate cancer at the time of initial diagnosis [5–7]. Optimal treatment for those diagnosed with high-risk prostate cancer is controversial, and the role of radical prostatectomy for locally advanced high-risk prostate cancer remains a topic of debate due to several reasons, including discouragement of surgical management and evasion of RARP because of inexperience with the technique and potential difficulty in performing extended pelvic lymph node dissection [20]. Therefore, long-term oncologic outcomes of RARP in patients with high-risk prostate cancer remain poorly reported.
Several series have recently reported the role of RARP in patients with high-risk prostate cancer. Despite its aggressive behavior, the prognosis of high-risk prostate cancer is not uniformly poor. High-risk prostate cancer is confined to the prostate in many patients, who may experience long-term progression-free survival after radical prostatectomy. Yossepowitch et al. analyzed radical prostatectomy outcomes in 957 patients with clinically localized high-risk prostate cancer and found that the cancer was confined to the prostate in 43% of the patients [21]. Compared with low- and intermediate-risk patients, there was a 3.3-fold increase in relapse hazard and higher likelihood of progression at five and ten years after radical prostatectomy. A multicenter study by Sooriakumaran et al. concluded that radical prostatectomy for patients with resectable distant metastases was safe in expert hands in the setting of meticulous patient selection [22]. The adoption of radical prostatectomy as a treatment option for high-risk prostate cancer was based on the reported overall (and disease-specific) survivals rates of 87% (93%), 70% (83%), and 58% (71%) at 5, 10, and 15 years, respectively [23].
The big question remains whether radical prostatectomy is superior to radiotherapy combined with hormonal therapy. Several studies retrospectively compared radical prostatectomy with radiotherapy. Boorijian et al. retrospectively compared outcomes between radical prostatectomy and radiotherapy combined with hormonal therapy in patients with high-risk prostate cancer and found comparable 10-year cancer-free survival rates between the two groups; the authors also found that the risk of all-cause mortality was greater after radiotherapy with hormonal therapy compared to radical prostatectomy [24]. Zelefsky et al. found that cancer-free survival rates were comparable between radical prostatectomy and radiotherapy combined with hormonal therapy in patients with high-risk prostate cancer [25]. In that study, the absolute benefit of 7.8% in distant metastasis-free survival favored radical prostatectomy. Radical prostatectomy is therefore superior to radiotherapy combined with hormonal therapy in healthy patients with long life expectancy. Additionally, Boris et al. demonstrated the feasibility and durability of salvage RARP after failed radiotherapy and reported that the functional and oncologic outcomes of RARP were not inferior to those of open radical prostatectomy [26]. Based on these results, we suggest that, when feasible, RARP should be considered in patients with organ-confined high-risk prostate cancer if the patient accepts the surgical risk. Salvage RARP is another good option for the treatment of patients with organ-confined high-risk prostate cancer after failed radiotherapy.
In the present study, the median operative time was 185 minutes and the median intraoperative blood loss was 200 mL; only one patient with cardiovascular disease received intraoperative blood transfusion. These findings are not substantially different than those reported in a systematic review of RARP outcomes in patients with high-risk prostate cancer [6]. The study reported that the mean operative time was 168 min, the estimated blood loss was 189 mL, the mean length of hospital stay was 3.2 days, and the duration of catheterization was 7.8 days. In the present study, the median duration of hospital stay and urinary catheter indwelling was seven days due to nature of the Korean medical insurance. Advantages of these long hospitalizations include the prevention of postoperative complications such as ileus and lymphocele.
The continence rates in the current study were consistent with the findings of other study that demonstrated the benefits of early recovery of urinary continence in patients with low- or intermediate-risk prostate cancer undergoing RARP, such as a report by Student et al. who found similar continence rates (62.5%, 68.8%, 75.0%, and 86.7% at 1, 2, 6, and 12 months, respectively) [27]. We performed the detrusorrhaphy technique which is designed for thickening and strengthening the detrusor muscles from the posterior bladder neck to the bilateral dissected pedicles area; this technique is thought to prevent hyper-mobilization of the bladder neck area, thereby reducing stress urinary incontinence, and is considered important for continence recovery as we previously reported [28]. Furthermore, using a validated sexual function questionnaire, we found that the rate of return baseline preoperative sexual function scores was 11.1% one month after RARP, which subsequently increased to 18.9%, 38.9%, and 56.7% at 3, 6, and 12 months after RARP, respectively. These outcomes are better than those reported by other studies using the same validated questionnaire in patients undergoing RARP. In their study examining nerve-sparing in salvage RARP, Bonet et al. reported that the 12-month potency rate was 25.6% in the good nerve-sparing group and that good nerve-sparing tended to be predictive of potency after salvage RARP [29]. In the current study, we performed athermal clipless intrafascial nerve-sparing technique if indicated; this technique might be associated with improved viable tissue preservation within the neurovascular bundles as we previously reported [28].
In the present study, the rate of patients with stage pT2 organ-confined prostate cancer by postoperative pathologic assessment was 31.3%, similar to that reported in the systematic review of RARP-related outcomes by Yuh et al., who found that the average rate of organ-confined disease was 35% (range, 7–48%) [6]. During the 3-year follow-up period in the present study, 43 of the 90 patients (47.8%) did not require secondary therapy such as radiotherapy or hormonal therapy. The rate of PSMs in the current study was 27.8%, in line with previous reports, as revealed in the systematic review by Yuh et al., in which the rate of PSMs was 35% (range, 12–53%) [6]. The rate of PSMs was reduced to 8.9% in the patients with stage pT2 disease. In the present study, the median follow-up duration was 51.5 months. Of the 21 patients (23.3%) who experienced BCR at a median of 10.5 months after RARP, 9 and 12 patients received adjuvant therapy and salvage therapy, respectively. Comparable to the present study findings, Kumar et al. reported that the overall BCR rate was 19.2% during a mean follow-up duration of 24.3 months and that the mean time to BCR was 7.9 months in patients with high-risk prostate cancer [30]. Our analyses revealing 3-year BCR-free and CR-free survival rates of 85.5% and 90.8%, respectively, are comparable to those reported in a study of patients with high-risk prostate cancer by Rogers et al. [31].
In patients with high-risk prostate cancer, RARP should be performed by skilled and experienced surgeons rather than beginners to reduce complications and to achieve optimal surgical results, given that radical prostatectomy is associated with high morbidity. A study by Punnen et al. provides further support for the effect of surgical experience on improved outcomes with RARP in patients with high-risk prostate cancer [32].
The limitations of the present study are the retrospective and noncomparative design of the study, which was performed by a single surgeon in a single institution, and the small sample size. While the present study was not a randomized trial, we believe that the biases associated with the study design were minimal, given that the surgeon has already performed more than 1000 RARPs between 2007 and 2020 and that the surgical methods in patients with high-risk prostate cancer are not challenging. Despite the ongoing follow-up of the study patients, our initial results suggest optimal functional and oncologic outcomes with RARP in patients with high-risk prostate cancer. Future studies should be conducted to include larger cohorts with longer follow-up periods to concomitantly compare the functional and oncologic outcomes of RARP with radiotherapy and/or hormonal therapy in patients with high-risk prostate cancer in a standardized fashion.