Pentafecta Outcomes of 230 Cases of Robotic-assisted Radical Prostatectomy with Bilateral Neurovascular Bundle Preservation

Discussion

The present study is the first in Asia to report pentafecta outcomes following 230 cases of RARP with bilateral NVB preservation performed by a single surgeon at a high-volume Center. The isolated continence, potency, and BCR-free rates were reached in 98.3%, 86.1% and 92.6% of patients, combined with trifecta rates achieved in 81.7%. In addition to the complication-free status (93.9%) and NSM (77%), the pentafecta rate was 60.4%. These findings are comparable to the results of our mentor, Dr. Patel (6). Side-by-side comparison of Dr. Patel's series and the present series is shown in Table VIII. Patients' in Dr. Patel's series had lower median PSA levels than in our series (4.4 versus 7.4 ng/ml). Statistically significant differences (all p<0.001) were found in age (58.57±7.532 versus 62.5±6.7), clinical T1 stage and low-risk category in Dr. Patel's series versus ours. However, the continence, potency, BCR-free, trifecta and complication-free rate between the two series were similar. The NSM was significantly higher, resulting in a higher pentafecta rate in Dr. Patel's series than in ours (70.8% versus 60.4%, p<0.05). Among Patel's patients, some of those who were ideal candidates for RARP with bilateral NVB preservation would have undergone active surveillance (13). In Taiwan, where there is no PSA screening program, more cases of prostate cancer are diagnosed at advanced disease and a large percentage (49.3%) of high-risk patients undergo RARP (1). In the present series, 14.3% of patient were considered at high risk, and RARP with bilateral NVB preservation can jeopardize surgical margins in these patients. In our previous study, the PSM rate increased from 43.9% in non-NVB preservation to 84.1% in NVB preservation among high-risk patients (p<0.01) (14). In other words, NVB preservation during RARP for the high-risk group increased PSMs. Srivastava et al. used a risk-stratified grade to adjust the nerve-sparing procedure during RARP (15). Similarly, von Bodman et al. advised that nerve-sparing techniques were performed during RARP according to intraoperative frozen section of the prostate to reduce the PSM rate (16). Among 904 patients undergoing RARP, Sooriakumaran et al. reported that unifocal PSMs of ≤3 mm were not significantly associated with BCR(5). However, those authors suggested that patients with >3 mm/multifocal PSMs may have a higher risk (2.84-fold) of BCR than those with unifocal PSMs of ≤3 mm, or NSMs, especially if they have lower-risk disease (5).

The course of progress made in learning RARP includes five parameters, out of which the first is no perioperative complications. Previously, we reported that experience of 150 cases are needed to reduce perioperative complications (9). The return to urinary continence can be better after the experience of 100 cases of RARP (17). The learning curve to achieve good potency and cancer control (NSM and BCR-free) is partially dependent on the patient cohort, including patients' age, PSA level and risk classification. Good et al. reported analysis of the pentafecta learning curve for LRP, including multiple learning curves for initial perioperative outcomes (150 cases), oncological outcomes (150-200 cases), then continence (200-250 cases), and finally over 250 cases to stabilize the potency outcomes (18). Our data did not show differences in the pentafecta rates of RARP between group I and group II. The reasons may be that group I (115 cases) was selected from 375 cases, and we crossed the pentafecta learning curve during this period. The second reason is likely age differences, since group II had statistically significant older age than group I (63.4±7.1 years old versus 61.6±6.1 years old, p=0.038) (Table I). The failed pentafecta group was also statistically significantly older than the group achieving pentafecta (63.6±6.4 versus 61.8±6.8 years old, p=0.041). Likewise, Dr. Patel et al. reported that patient age proved to be the only parameter independently associated with pentafecta outcomes after RARP when analyzed using multivariable analysis (6). On univariable analysis, patient age and pathological stage were the two factors that influenced achieving the pentafecta (6). Our results showed that the ratio of pT2 to pT3 was 78.4% to 21.6% in the group achieving pentafecta and 42.9% to 57.1% in the failed pentafecta group (p<0.001). Our results revealed that the pathological stage is a factor associated with achieving pentafecta, which is compatible with Dr. Patel's comments. Undoubtedly, our data reflect 57.1% of pT3 and 58.2% of PSM in the failed pentafecta group. Ploussard et al. analyzed 1,504 consecutive men undergoing radical prostatectomy, of which 73.7% of patients with PSM versus 93.0% of patients with NSM (p<0.001) achieved 2-year BCR-free survival (19). PSM does not influence BCR in pT2 disease. In pT3 disease, PSM length (≥3 mm) and multifocality (≥3 sites) are significantly related to poorer outcomes (19). Si-Tu et al. also reported 170 cases of LRP and noted that multivariable analysis revealed that patient age and pathological stage are two independent factors that can predict pentafecta (20).

Minimally-invasive surgery (e.g. LRP and RARP) is the trend of treatment forlocalized prostate cancer. Patients have high expectations for functional and oncological outcomes. Dr. Patel advocated the new concept of pentafecta outcome after RARP (6), which is a patient-oriented consideration. Pentafecta rates can depict postoperative patient satisfaction and provide a more comprehensive tool for counseling patients undergoing RARP (6). However, the new concept has not yet been widely adopted. In Table IX, we review pentafecta outcomes of four series of RARP and three of LRP in a world series (6, 18, 20-22). The case numbers ranged from 91 to 335. RARP was performed by multiple surgeons in two series, while one surgeon performed RARP in Dr. Patel's series and the present series. Briefly, in that comparison of series, the overall continence rate ranged from 81.3% to 98.3%, with LRP varying from 81.3%-97.1% and RARP having the higher rates (87.5%-98.3%). Moreover, the overall potency rate ranged from 39.6% to 89.8%, and similarly, LRP had greater variation (39.6%-75.3%), whereas RARP achieved 59%-89.8%. The overall BCR-free rate ranged from 87.5% to 100%, with LRP representing the high scale (89.4%-100%), followed by RARP (87.5%-96.4%). The complication-free rate ranged from 81.1% to 93.9%, including 81.1%-93.9% in the LRP series and 87.9%-94.7% in the RARP series.The NSM rate ranged from 76.5% to 90.7%, similarly in both LRP (75.6%-94.7%) and RARP (77%-90.7%). Lastly, the pentafecta rate ranged from 27.5% to 72.9.%, with 27.5%-72.9%in LRP and 45.6%-70.8% in RARP. Based on these data, we can illustrate the pentafecta rate for counseling patients before surgery. As in our previous publication, the major concerns for patients undergoing RARP were cancer control, followed by postoperative continence rate, then less pain, less blood loss and preservation of erectile function (23). Sometimes, preserving the neurovascular bundle can result in positive surgical margins and BCR development. Therefore, patient selection is a very important point, along with low-risk disease and younger age, which appear to achieve higher pentafecta based on our data.

This study has several limitations. The functional outcomes, including continence and potency, were mainly determined via physician assessment rather than by patient questionnaire. Using the continence definition of pad-free status, the correlation between patient-reported and physician-reported assessments was high (24). For potency evaluation, potency was defined as an erection sufficient for intercourse with (N=75) or without (N=123) PDE-5 inhibitors, achieved in 86.1% (198/230) of cases. In addition, the follow-up period was relatively short-term (mean=24 months), which should be extended to intermediate- and long-term follow-up in order to confirm functional results and BCR-free survival.