With the widespread use of prostate-specific antigen (PSA) screening, a majority of prostate cancers are diagnosed in the early stages (1,2). Combination with multiparametric magnetic resonance (MP-MRI) helps better estimate the prostate cancers and guides the treatment approaches (3). Radical prostatectomy (RP) is regarded as a standard treatment for localized prostate cancer. Although effective at cancer control, RP has several common complications including erectile and urinary dysfunction, which severely affects the quality of life. Therefore, the trifecta outcome (cancer control, urinary continence, potency recovery) has become the most desired outcome following RP. The nerve-sparing (NS) modification of RP is required for maintaining sexual functioning after surgery (4). The necessary surgical procedure of NS-RP is to maintain the integrity of the neurovascular bundle (NVB). The distance between the ipsilateral neurovascular bundles (NVBs) and foci of prostate tumor (the N-T distance) (5), measured in specimen removed by RP, is a practical way for determining indications that warrant the use of NS-RP. However, the N-T distance is a postoperative measurement tool, and we still need preoperative clinical indications. In this study, we propose the clinical indications of NS-RP and discuss the clinical safety and feasibility.

Radical prostatectomy (RP) is the main surgical treatment for localized prostate cancer, and nerve-sparing (NS) is recognized as a critical surgical procedure to preserve or restore erectile function. NS-RP improves sexual function and restores urinary continence, but it might increase the positive rate of the surgical margin (7,8). Until now, the indication of NS-RP remains ambiguous.

Previous studies suggested that the intraoperative visual and tactile examination of epfascial sclerosis nodule could be the determination on whether to spare the nerve in RP or not (9). However, due to open surgery being substituted by laparoscopic surgery, depending on intraoperative examination was not practical and precise. Furthermore, in some studies (5,10–12), the extra-prostatic extension (EPE) in the region of NVB was regarded as one of the most important clinical variants for NS-RP or not. Naya et al. (10) reported that the strongest preoperative independent predictors of the EPE were the maximum tumor length ≥7 mm and positive basal core location. Tsuzuki et al. (11) showed that PSA (>10 ng/ml), biopsy Gleason score (>7), average percent involvement of each positive core (>20%), percent of side-specific biopsy cores with tumor (≥1/3), and abnormalities in the rectal examination were statistically significant independent predictors of EPE in the NVB. However, rather than adopting the EPE in the NVB as a criterion, the N-T distance (>2 mm) in postoperative pathologic specimens was used in our study.

We suggested the N-T distance (>2 mm) as the criterion based on the following reasons: (I) the N-T distance is not only associated with PSM but also a more objective indicator, compared with the extra-prostatic extension. Therefore, using N-T distance as the criterion to evaluate NS is more consistent with the clinical principles of cancer control. (II) The network of nerve fibers and extra-capsular tumor cells are both microscopic, thus their anatomical structures are hard to be recognized visually. Despite using the three-dimensional DaVinci system, which magnifies the field by 10–12 times, their anatomical structures are still difficult to visualize intraoperatively, leading to more possibility of PSM. As a result, to keep the balance between tumor control and nerve-sparing, using the N-T distance from the postoperative specimen is a more objective indicator. (III) Sung et al. (13) demonstrated that the average distance from the prostatic capsule to nerve fibers was 1.73 mm in the ventral part, 1.80 mm in the dorsal (rectal) part, 1.58 mm in the right lateral part, and 1.23 mm in the left lateral part (p = 0.266). Also, no significant difference was observed among the base (1.62 mm), mid-part (1.41 mm), and apex levels (1.72 mm) (p = 0.673). Inoue et al. (5) reported that the mean N-T distance with EPE was 2.01, 1.95, and 1.85 mm in the apex, middle, and base, respectively. Therefore, PSM was very likely to occur when performing NS-RP when the N-T distance was <2 mm. (IV) In our previous study related to the network of nerve fibers under endoscopic technique, the network was divided into two groups and five zones. The most vulnerable areas were the peri-seminal vesicle reticulum (zone 1), NVB (zone 2), and bilateral prostatic network (zone 3). Through autopsy, we found that the nerve network in the ventral 12-point region of the pelvic fascia around the prostate was sparsely distributed and other regions were equally distributed. Hence, measuring the N-T distance in the NVB region as the criterion was anatomically appropriate. (V) Previous research showed that EPE happened in the NVB region and easily caused PSM (14,15). In our study, the percent of PSM happened in the NVB region and the base of the prostate was 89% (8/9). Thus, regarding the N-T distance as the criterion was consistent with the pathophysiology of prostate cancer.

Previous studies found that the EPE was associated with the percent of side-specific biopsy cores with tumor (≥1/3), preoperative PSA level, and biopsy Gleason score (5,14–17). Preoperative MP-MRI (18,19) is also related to EPE and is used to estimate the risk category of prostate cancer (3,20). Our study used the N-T distance (2 mm) as the criterion for NS-RP and predicted its associated preoperative clinical variants. The result showed that only the percent of side-specific biopsy cores with tumor (≥1/3) and preoperative MP-MRI examination were the independent risk variances. Based on the above results, we suggested that the preoperative indication of NS-RP was percent of side-specific biopsy cores with tumor (<1/3) and no extra-capsular extension by MP-MRI examination, even though PSA level >10 ng/ml or biopsy Gleason score >8 in clinical T2c cases.

Our study still had some limitations. The samples were relatively small due to exclusion of cases undergoing bilateral NS surgery, leading to selective deviation. For those bilateral NS cases, lacking neural markers resulted in the unreliable measurement of the N-T distance. Instead, we measured the distance between the posterolateral region of the prostate and tumor (<2 mm) as substitution and finally got similar results. We must point out that it remains to be further demonstrated the rationality of adopting the N-T distance (>2 mm) as the NS-RP criterion. Furthermore, more prospective studies should be designed to evaluate the above preoperative factors as the criterion of the NS-RP.

For the patients with radical prostatectomy, percent of side-specific biopsy cores with tumor (<1/3) and no extra-capsular extension by MP-MRI examination can be regarded as preoperative indications for nerve-sparing surgery when we defined the distance between a tumor and neurovascular bundle >2 mm as the nerve-sparing criterion.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the ethics committee of Jinhua Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

ZZ: study design, collecting of clinical data, and writing of the article. YZ: patient follow-up and collecting of clinical data. YX and SH: conducting of the statistical analysis. All authors contributed to the article and approved the submitted version.

This work was supported by grants from the Basic Public Welfare Research Project of Zhejiang (LGF18H050006) and the Major Research Program of Jinhua Science and Technology (2021–3–022).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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