RARP offers potential benefits such as a low PSM rate compared with open RP owing to better visibility and less blood loss 19,20. In our series, the overall PSM rate was 30.1%, which is a higher rate than that reported in high-volume RARP studies, in which the range typically was 10.8–22% 21. This may be attributable to a much higher percentage (56.6%) of patients in the pT3 stage in our study than in other studies, where the percentage of pT3 stage patients ranged from 9.3 to 37.5% 21.
We determined the major preoperative predictor for the PSM rate to be PSA > 10 ng/mL. The predictors of the ISUP score upon biopsy and the cT stage defined through MRI did not exhibit a positive correlation in multivariate analysis. Liss et al. assessed 216 cases of RARPs and concluded, similar to us, that the preoperative predictive factor of PSM was PSA level instead of cT stage and ISUP score 22. The author explained this phenomenon because a portion of patients was transferred from other hospitals; thus, biopsy methods and MRI outcomes were not standardized, potentially yielding different results. Another reason we proposed may be the high pathological ISUP (43%) and T stage (30.2%) upgrading rate from biopsy to prostatectomy in our database. These factors may limit the precise prediction of the postoperative PSM rate through the use of the preoperative cT stage and ISUP grade.
Estimated blood loss > 200 mL is a significant intraoperative predictor of the PSM rate, and we speculated that intraoperative bleeding would hinder clear visualization from identifying prostate margins and prolonging the surgical time. In our study, further analysis found the operative time was longer among patients with an estimated blood loss of > 200 mL than in those with an estimated blood loss of ≤ 200 mL (mean: 303 min vs. 235 min, respectively). Kim et al. determined that higher blood loss was associated with larger prostate size in a series of 1168 RARPs. Nevertheless, the final PSM rate did not significantly differ among divided-size subgroups 23. Tamhankar et al. reviewed 1406 RARPs to determine the steepness of the surgical learning curve reflected by the extent of blood loss and reported a 70% reduction in blood loss from the start to the end of the training period. However, the surgical time and the number of cases were not associated with the risk of PSM 24.
Individualized surgical experiences may influence RARP performance. Several studies have reported that the PSM rate is inversely proportional to the number of surgical cases 25–28. In our study, a single surgeon with extensive prior experience in laparoscopic surgery performed the surgeries; consequently, the PSM rate was almost the same at approximately 30% per 100 cases. This finding suggests that the surgeon’s previous experience in minimally invasive surgery can minimize the risk of PSMs when using a robotic surgical approach. White et al. reported a single-urologist case series and revealed that extensive previous experience in ORP might potentially prevent an increase in the PSM rate during the initial learning curve in RARP 29.
The pT3 stage predictor was significantly correlated with a high PSM rate according to previous reports 21,22,30−33. Ficarra et al. studied 322 RARPs and reported that the pathological findings of extraprostatic extension (EPE) were the only relevant PSM predictor 34. Previous studies have reported that T upstaging rates varied widely from 4.5–68% of cases 35,36. In this study, T upstaging occurred in one-third of cases, suggesting that preoperative understaging data may result in underresection of prostate tumors. In particular, the ISUP grade at RP is not considered an independent predictor, implying that total resection of high-grade tumors can be accomplished without leaving positive margins. A Partin table is a useful tool developed at John Hopkins Hospital for evaluating the risk of EPE before prostatectomy on the basis of preoperative PSA, ISUP, and clinical stage 37. However, in our data, only preoperative PSA level was significantly associated with EPE in multivariate analysis. The discrepancy of preoperative ISUP and clinical stage in pathological reports of RP specimens may reduce the utility of preoperative parameters for predicting postoperative PSM.
Kang et al. reported the distribution of surgical margins in high-risk PCa, with positive rates of 16.2% in the apex, 14.7% in the bladder neck, 38.2% in posterolateral regions, and 26.5% in multifocal regions 30. For our study, the majority of PSM is 73.8% in the posterolateral, 27.7% in apical and 13.5% in bladder neck regions. Previous studies have reported that the high PSM rate occurs in the posterolateral area, especially for high-risk pT3 diseases 30,38. Eastham et al. reported large amounts of neurovascular tissue over the posterolateral region, potentially enhancing tumor cell migration and promoting local invasion 39; furthermore, the BCR rate was higher among individuals with posterolateral PSM than in those with NSM (HR: 2.80). The NS procedure is associated with the PSM in the posterolateral region 22,40, potentially explaining the high technical skill needed for successful dissection of the correct planes of fascia. However, the current results demonstrated that the NS group had a lower risk of PSM in the posterolateral region than the non-NS group did (3% vs. 20%). This is probably because of the higher percentage of patients in the pT3 stage than in the pT2 stage in the non-NS group (79% vs. 21%), which may be more influential than NS techniques.
Previous studies have been reported the apex is the most frequent region of PSM in RP specimens 31,41. This is attributable to the unclear prostate capsular margins, which are difficult to identify in pT2 and pT3 stages 38. More other studies have reported that apical PSM is correlated with the surgeon’s approach and skills rather than the tumor stage 21,26,41. The surgeon in this study has extensive laparoscopic experience, explaining the relatively low rate of PSM in the apex. The estimated blood loss was significantly higher among patients with apical PSM, which implies potential bleeding from the dorsal vein complex upon dissection of the apical prostate 42. Coelho et al. reported that high BMI was a predictor for apical PSM in a cohort study involving 876 RARPs 31, and our study determined that high BMI was significantly associated with higher odds of PSMs at multifocal regions (p = 0.025) but not apical regions.
Koizumi et al. reported that employing the RARP approach has a higher likelihood of leading to PSM at the bladder neck than either ORP or LARP do 29. This is possible because of the excessive preservation of bladder neck tissue to secure postoperative urinary continence 15. Furthermore, the presence of a prominent median lobe during surgery might increase the risk of PSM over the bladder neck (p = 0.047), indicating the challenging task of identifying surgical margins between the protruding prostatic lobe and bladder neck.
Several studies have reported patients who underwent prostatectomy with a 5-year BCR-free survival rate ranging from 74–87% and a median PSA recurrence time of 2.6 years 43–45. In this study, the 5-year BCR-free survival rate was 66.7%, which was lower than that reported in other studies; this is probably owing to the higher ratio (53%) of aggressive pT3 disease at the outset of the accumulation of RARP cases. Evidence supports the characterization of PSM as a strong predictor of disease progression 46–48. Our data indicate that the hazard ratio for PSM with BCR is 1.725 (p = 0.027). Recently, Zhang et al. performed a systematic review and meta-analysis, wherein they included 38000 patients and determined PSM to be an independent factor with higher BCR in multivariate analysis (p < 0.001, pooled HR 1.35) 6. Ploussard et al. analyzed a prospective study including 1943 RPs with a mean follow-up of 68 months and suggested that PSM was a significant predictor of BCR, the need for salvage therapy, and even cancer-related death. However, PSM was significantly correlated with BCR at stage pT2 and pT3a disease but not pT3b stage disease 48. PSM's effect on BCR in stage pT3b disease was reportedly weak owing to a markedly higher risk of micrometastatic lesions, which are more influential than PSM is. Similarly, our study's PSM effect was nonsignificant in the pT3 stage compared with the other two predictors, PSA and ISUP grade.
In particular, among men who underwent RARP with postoperative PSM, an ISUP grade > 3 at RP (p = 0.002, HR 2.689) was the sole predictor of BCR-free survival regardless of pT stage and PSA concentration. Karakiewicz et al. reported similar results among 5831 RPs, indicating that the PSM group had a 3.7-fold higher risk of progression, particularly in the group with tumors at an ISUP grade > 2 in PSM 47. Furthermore, Kang et al. reported that pathological ISUP grade > 3 was a predictor for BCR (p = 0.047, HR 4.180). These results suggest that disease progression depends on the PCa tumor grade in surgical margins 49. Moreover, Stephensen et al. reported the effect of the number and extent of PSM on BCR, indicating that a mildly increased risk of BCR is significantly correlated with multifocal and extensive PSM 50. However, we did not analyze the effect of PSM's extent; the current evidence is inadequate to differentiate the effect of unifocal and multifocal PSM on BCR-free survival. The residual low-grade tumors on PSM may not increase the BCR rate. Our study’s surgeon used electrocautery methods when dissecting the prostate fascia, thus indirectly decreasing the residual tumors on margins and reducing PSA recurrence risk. Furthermore, in Asian countries, the incidence of PCa is relatively low; however, the type of PCa typical to Asia is more aggressive than that in Western countries 18,51. A high percentage of PCa patients have pT3 stage disease in prostatectomy, which may reduce the influence of PSM in terms of PCa progression.