In this study, we determined BCR-free survival rates and the incidence of postoperative urinary incontinence in high-risk/very high-risk and below high-risk localized prostate cancer patients after RaRP. We found that high-risk and very high-risk patients had shorter BCR-free survival than below high-risk prostate cancer patients. The high-risk/very high-risk group without adjuvant treatment had significantly worse BCR-free survival than the high-risk/very high-risk group with adjuvant treatment and the below high-risk group. The rate of SUI trended down from 50.7% at postoperative week one (immediately after removal of the urethral catheter) to 8.5% at postoperative month 12. Compared with the below high-risk group, the high-risk/very high-risk group had significantly higher SUI rates at postoperative week 1 and month 1 and comparable SUI rates at postoperative month 12. Additionally, high-risk/very high-risk was a significant predictor for immediate postoperative SUI but not for long-term SUI in multivariate analysis. Considering the oncological and functional outcomes, RaRP can be considered a safe and feasible option for high-risk and very high-risk prostate cancer patients.
High-risk/very high-risk prostate cancer patients had a worse BCR-free rate than their low- and intermediate-risk counterparts after radical prostatectomy. Reese et al. have reported a 10-year BCR-free rate of 92.1% in low-risk patients, 71.0% in intermediate-risk patients, and 38.8% in high-risk patients after radical prostatectomy [13]. The overall BCR rate in high-risk patients with locally advanced prostate cancer ranged from 13–35% and 18.5–28.6%, respectively [5, 6]. Koo et al. found that 77% of high-risk and 58% of very high-risk patients were free from BCR at final follow-up, with median follow-up durations of 31.1 and 36.1 months, respectively [9]. Gandaglia et al. reported a 3 year BCR-free survival rate of 63.3% in patients with at least cT3 localized prostate cancer [10]. In our study, the 3 year BCR-free rate in high-risk/very high-risk patients was 46.9%, which was lower than that seen in the aforementioned studies. There are several possible reasons for this. In our study, we performed RaRP and standard pelvic lymph node dissection and the enrolled high-risk/very high-risk patients had a higher median PSA level (26.5 ng/mL). Nevertheless, Gandaglia et al. reported data from RaRP and extended pelvic lymph node dissection in locally advanced prostate cancer patients with a median PSA level of 9.7 ng/mL. More severe oncological factors (indicating greater tumor burden and involvement) and less extensive lymph node dissection might explain the lower BCR-free survival rate in our study.
Adjuvant radiotherapy plays an important but controversial role in BCR in high-risk/very high-risk prostate cancer patients who undergo RaRP. Thompson et al. have reported an average of 10.3 years of PSA-relapse-free survival in patients who received radical prostatectomy followed by adjuvant radiotherapy but only 3.1 years in those without adjuvant therapy [14]. In a retrospective review of 26118 localized prostate cancer patients, adjuvant radiotherapy was associated with significantly lower all-cause mortality than early salvage therapy in patients with adverse pathology (pN1, pGleason scores of 8–10, pT3/4) [15]. By contrast, several randomized controlled trials in 2020, including the phase III RADICALS-RT trial and GETUG-AFU 17 trial, found that adjuvant radiotherapy had no significant benefits to survival but led to a higher rate and severity of long-term urinary incontinence compared with early salvage radiotherapy [16, 17]. In our study, high-risk/very high-risk patients who underwent RaRP had similar operation times and blood loss to the below high-risk group. Additionally, high-risk/very high-risk patients who received adjuvant treatment (including radiotherapy and/or ADT) after RaRP had significantly better BCR-free survival than those who did not, with BCR-free survival comparable with that of below high-risk patients. This result favors the selection of RaRP as an initial step in a multimodal treatment strategy (followed by adjuvant or salvage treatment) in high-risk and very high-risk prostate cancer patients and suggests that this is a safe approach with improved oncological outcomes.
Functional urinary incontinence outcomes reported in high-risk/very high-risk patients who undergo RaRP have varied between studies. Casey et al. have reported rates of 85% and 100% continence at postoperative months 6 and 12 in pT3 prostate cancer patients after RaRP [8]. Koo et al. have reported 56% and 32% continence rates at postoperative month 12 in high-risk and very high-risk patients, respectively [9]. Gandaglia et al. reported a 64% near-continence rate 12 months after RaRP, with no or one pad per day, in patients with locally advanced prostate cancer [10]. Varied definitions of continence among these studies may explain the inconsistent continence rates. In this study, the definition of SUI was based on the criteria of the International Continence Society, and the overall SUI rate at postoperative month 12 was 8.5%, which is in accord with the general level [18]. There was no significant difference between the below high-risk group and high-risk/very high-risk group patients. Our results suggest that RaRP is a feasible option in high-risk and very high-risk localized prostate cancer patients that does not impede the recovery of long-term continence.
The continence mechanism in men is controlled by the prostate gland, urethral sphincteric system, and urethral supportive system [19]. After radical prostatectomy, the remaining functions of the urethral sphincter and supportive system play important roles in the recovery of urinary continence. However, maximal preservation of the urethral sphincter and the supportive system cannot always be achieved in high-risk and very high-risk patients because of the high risk of extraprostatic expansion and the need for pelvic lymph node dissection. In this study, high-risk/very high-risk was the only independent predictor of SUI at postoperative week 1 but was not predictive at postoperative month 12 in multivariate analysis. The advanced intraoperative and precise dissection techniques used in robotic surgery might decrease the impact of reduced preservation of the urethral sphincter and supportive system. Thus, high-risk/very high-risk only affected early recovery, not long-term recovery, of urinary incontinence.
Previous studies have identified several biological and preoperative predictors of urinary incontinence after radical prostatectomy, including older age [20, 21], high BMI [22], comorbidities [20], increased prostate volume [23], pre-existing lower urinary tract symptoms [22], bladder and sphincter dysfunction [24], and a history of TURP and radiotherapy [25]. Perioperative predictors that have been identified include a less experienced surgeon [26]; damage to, or non-nerve sparing of, the neurovascular bundle [27]; excessive surgical dissection [25]; and adjuvant/salvage radiotherapy [28]. In this study, a higher TPV, a high biopsy Gleason score (≥ 8), and a positive surgical margin were found using the univariate analysis to be predictive of SUI at postoperative month 12. No significant predictive factors for either SUI at postoperative month 6 or 12 were identified using the multivariate analysis. Postoperative SUI is a complex summary display affected by the above preoperative and perioperative factors. With the advancement of surgical techniques, the effects of these factors may be expected to lessen.