Similar Recurrence Rate Between Gleason Score of Six at Positive Margin and Negative Margin After Radical Prostatectomy

Discussion

It has been reported that RARP reduces BCR compared with conventional surgical methods. Some reviews showed that compared with the conventional surgical methods, RARP could not reduce the risk of PSM (1, 2); other reviews show that RARP decreases the risk of PSM in patients with T3 or high-risk groups (1, 2, 10). In this study, we aimed to investigate the relationship between the PSM and BCR in the robot age. In our study, the BCR-free survival rate at 5 years was 79.3%. Several articles have demonstrated that the BCR-free survival rate at 5 years was between 80.1-87.1% (11-13). The results in this study were comparable to the BCR-free rates reported in past reports. Surgeon volume, preoperative PSA, PSA density, biopsy GS, pathological stage, postoperative GS and SM have been reported to be predictors for BCR in multivariable analyses (11-13). In our study, preoperative PSA, biopsy GS, clinical stage, pathological GS, and SM status were predictors for BCR in multivariable analyses. In recent years, it has been reported that the identification of subclassifications of PSM, such as PSM length and GS at the PSM, were important for improving the BCR prediction (7, 14). Moreover, this information might be useful for patient counseling and the follow-up schedule. In previous studies, PSM length, PSM location and GG (or GS) at the PSM are often taken up as predictors. Therefore, we focused on these three factors in this study.

First, regarding the PSM length, Shikanov et al. reported the PSM length as a continuous and categorical variable (<1, 1-3, >3 mm), showed it was an independent predictor and found similar BCR rates in patients with PSM <1 mm and in patients with NSM (5). Preisser et al. showed that a PSM ≥3 mm was an independent predictor in multivariable models (7). In our study, there were no statistically significant differences between the NSM and PSM ≤3 mm; however, there was a statistically significant difference between the NSM and PSM >3 mm. Second, regarding PSM location, Gautier et al. reported that extensive apical PSMs significantly increased the risk of BCR (15). In contrast, Ploussard et al. reported that PSM subclassifications, including PSM location, do not improve the BCR prediction in organ-confined PC (6). Further, Stephenson et al. reported that location and extent of PSM did not improve the accuracy of predicting BCR (16). The definition of the locations of PSM, such as anterior, apex, base, lateral, or posterior of the prostate which did not have clear boundaries was ambiguous in all past studies. We did not select the location of PSM as a predictive factor in this study because of the difficulties of a clear definition of PSM location from our pathological findings. Finally, regarding GS at PSM, Iremashvili et al. showed that the presence of Gleason 4/5 pattern at the PSM was the most practical definition for high risk of BCR (17). Kates et al. demonstrated that higher margin GS (≥4+3) was associated with an increased risk of BCR, and that a lower GS at the margin than the final pathology GS was associated with a lower risk of BCR than if the final pathology and margin GS were the same (8). On the other hand, Preisser et al. reported that BCR free survival for Gleason pattern 3 at 72 months had a statistically significant difference vs. Gleason pattern 4 and higher. However, they could not find out whether the Gleason pattern at PSM is a predictor of BCR in a multivariate model (7). Evren et al. also could not find out whether the Gleason pattern at PSM is a predictor of BCR in a multivariate model (18). In our study, a GS equal to 7 or higher at the PSM had a significantly higher BCR rate compared with NSM and GS=6 at the PSM. In addition, there was no statistically significant difference between NSM and GS=6 at the PSM and the two groups showed a similar BCR free survival. In the present study, no less than 36.5% of the total PSM cases had a GS equal to 6 at the PSM.

The proportion of cases with a short resection margin was higher in GS=6 vs. GS ≥7 at the PSM. In the case of GS=6 at the PSM, there was no difference in the recurrence rate because of the difference in resection margin. The risk of resection length was relatively reduced when GS=6 at the PSM, which could be the one of the reasons why there was no significant difference in recurrence rate from cases with NSMs.

We have examined the details of the PSM for each factor, but in reality, each factor was thought to be closely related. Patients with worse GS at the PSM had longer PSM in this study; therefore, exacerbation factors may be related. PC with low volume (<0.5 cm3) and low grade (GS≤6) was classified as insignificant cancer according to the report of the Johns Hopkins group (19). Several large studies have reported that the rate of metastasis for GS=6 PC confirmed by RP specimen is close to zero (20). GS=6 PCs have a low risk of progression, and even if a few PCs remain in the PSM cases, they are very unlikely to be clinically problematic, which may be one of the reasons why there was no difference in BCR between NSM and GS=6 at PSM cases in this study.

So far, the pathological evaluation and report for GS at the PSM in RP specimen has not yet been established as standard pathological diagnosis. In fact, Iremashvili et al. reported that 85% to 88% of responders in a survey of the members of the International Society of Urological Pathology were not reporting the GS at the PSM (17). Improving the predictive accuracy of BCR has important clinical implications. To improve the accuracy of predicting BCR, it may be desirable to incorporate GS in PSM into the pathological evaluation of RP specimens, if a PSM is present. The American Urological Association/American Society for Radiation Oncology guidelines suggest that patients with PSM at RP should undergo adjuvant radiotherapy. However, radiation therapy is associated with an increase in the incidence of short- and long-term severe complications (21, 22). If accurate reports of the GS at the PSM become common, we can prevent patients with GS=6 at the PSM from experiencing the complications of unnecessary radiation. The nerve-sparing procedure was known to be associated with urinary incontinence prevention and preservation of sexual function (23); however, nerve-sparing was indicated to possibly increase the PSM rate (24). Some urologists may be strict in their indications for nerve-sparing to avoid getting a PSM. As shown in this study, that there was no difference in BCR rates between GS=6 at the PSM and NSM; the indication of RARP with nerve-sparing technique may be desirable in the GS=6 side, in addition to the non-cancer side of the prostate by systematic prostate biopsy, in order to obtain better urinary and sexual function.

This study had some limitations: its retrospective design, small sample size, short-term follow-up and lack of analysis of overall survival. In addition, the indication of lymph node dissection was ambiguous by the surgeon, which may affect the BCR rate. Moreover, location, extent and multifocality of PSM, which have the possibility of increasing the BCR rate, were not examined. The exact pathological stage could not be determined in all cases of our cohort because approximately 10% of the pathological specimens had positive SM in the absence of extra-prostatic extension (= pT2+); therefore, the risk of recurrence at the pathological stage could not be examined. However, finding no significant differences between GS=6 at the PSM and NSM, as shown in this report, would be useful in predicting BCR, and could have an impact on increasing the selection of patients for nerve preservation during RARP.