While achieving the “trifecta”—being cancer-free, continent and potent—is the commonly anticipated goal of many radical prostatectomy (RP) patients, issues such as urinary incontinence (UI) and erectile dysfunction (ED) are often realities that considerably impact their quality of life (QoL) [1]. The nervesparing (NS) RP, pioneered by Walsh et al. [1] in the 1980s, sought to reduce rates of UI and ED through careful dissection of the neurovascular bundles away from the prostate during prostatectomy. Initial reports comparing Walsh’s approach to its predecessor were promising and demonstrated improved urinary continence (UC). However, subsequent papers have painted a mosaic of results with variable rates of continence dictated by numerous potential confounders [2-9]. Such observations led us to question if NS RP was a clinically significant approach in our own patient population. With the exception of perineural invasion due to significant tumor burden, aggression, or extension, the NS RP is typically championed by urologic surgeons and educated patients [10].

Even if it is successfully performed, the positive effect of NS on postoperative UC is controversial. Some studies from the past decade have emphasized that NS approaches (1) should be performed whenever possible and within clinical reason [8], (2) reduce the time to regained continence [4], and (3) do not adversely affect pathologic outcomes [6]. To contrast, we and others have suggested that there is no significant difference between NS and non-NS procedures regarding long-term continence [5,7,11]. Tzou et al. [5] indicated that the similar outcomes of NNS and NS procedures might be attributable to large differences in data acquisition. Moreover, the heterogeneity of the definitions for continence, and especially for successful NS, further complicates this issue [12].

There is a discrepancy between the “intention to perform” NS and NS that is both successful and effective. Thus, from this, there are 2 possible ways to define NS. One definition is derived from the surgeon’s operative note (surgeon-defined), which is a subjective definition that does not necessarily prove that the essential nerves were successfully spared. A second definition is based on functional outcomes such as preservation of penile erections, which is only possible if the neurovascular bundles (NVB) were themselves preserved. This is an objective way of indicating a successful NS surgery [13,14].

We surmised that if NS did indeed have an effect on continence, then there must be a correlation between potency and continence. Therefore, we hypothesized that the most comprehensive definition of effective NS would be seen in the postoperative recovery of erectile function per the patient International Index of Erectile Function (IIEF)-scores (IIEF-defined). In consideration of the given endpoint of the study, we performed calculations for both surgeon-defined and IIEF-defined NS modalities. Here, we present the results of a prospective investigation on a cohort of patients who underwent RP at our institution over a 9-year period.

Between January 2004 and October 2013, 253 men underwent RP at our institution. Seventeen men did not complete preoperative questionnaires and were consequently excluded from the study. All clinical data from the remaining 236 patients were collected and compared. Applying our previously described quantifiable definition of continence (EPIC-UI>85), a Kaplan-Meier analysis demonstrated a cumulative continence rate of 76% for the entire cohort. At 1 year postoperatively, 53% recovered satisfactory continence; at 2 years, 61%; and at 3 years, 65%.

Though the pathogenesis of UI after RP for most patients is based on the presumed intraoperative destruction of the NVB as well as the innervated accompanying muscle tissue, the influence of NS RP on UC preservation remains controversial [3,9,19,20]. Initial reports comparing Walsh’s approach to its predecessor were promising, respectively demonstrating rates of continence as high as 85% versus 16% [21]. Yet, the analysis of over 3 decades’ worth of international NS prostatectomies has yielded a notable mix of results. Flynn and Webster [22] reported a high heterogeneity of outcomes, with post-RP UI spanning the low single-digits up to 74%. To that end, Sanda et al. [2] pointed to age, high PSA scores, and race as factors that affected post-RP UI rates. Reeves and colleagues suggested that NS RP ultimately resulted in earlier recovery of UC but at the 1- and 2-year follow-ups, there was no difference in the rates of continence between those who underwent NS RP versus those who underwent NNS RP [7]. In totality, such studies are highly variable with respect to their data analysis and interpretation [9].

Oftentimes, the available data assessing UI or NS are acquired in different descriptive manners and, at the same time, UI and NS often lack consistent definitions. UI for example, is often defined as being reliant on one or no pads, while NS is usually defined by the surgeon or pathology reports [3-9,12]. However, our study is based on self-reporting questionnaires; here, successful NS is defined by a satisfactory functional outcome regarding erectile function, which proves that the cavernous nerves were maintained and are functional. In another regard, strongly influencing variables such as age have not been recognized in many studies [23]. Lastly, the impact of modern surgical advances (such as laparoscopic- and robotic-assisted techniques) lack widespread systematic assessment with respect to UI. To this end, a recent publication demonstrated similar functional outcomes between open and robotic-assisted RPs [24].

Kundu et al. [20] assessed the impacts of NS and demonstrated similar results to ours. A positive association was seen between young age and preservation of continence, but none was seen between NS and the prevention of UI [20]. To contrast, Park et al. [6] analyzed a cohort of 360 patients, revealing significantly better UC rates with NS. However, they defined continence as requiring “no pad.” Slight differences from this definition, such as subjectively good continence despite the use of security pads during physical activity, were otherwise classified as “incontinent.” Furthermore, the study utilized only surgeon-defined NS statuses; histologic assessment of functional nerve preservation was not performed, and postoperative potency outcome was not reported. This methodology is congruent to several other studies but not all [3,8,25]. Other studies have defined NS in more unique ways. For example, in addition to using surgeon-defined NS statuses, Tzou et al. [5] performed a subgroup analysis with “successful NS” defined as one that ultimately yielded an erection “firm enough for intercourse.” Of note, this study did not demonstrate any influence of NS on UI. Taking all of this into account, we believe that the controversy surrounding the efficacy of NS RP on UC essentially lies with the definition of continence and the definition of NS. In an attempt to address this, we were the first to use the EPIC scoring system to quantitatively define continence [12]. EPIC allowed us to describe continence in a more nuanced fashion, versus simply relying on the binary definition of “pad” vs. “no pad.” In this study, we expanded upon our quantitative definition of UI by also quantifying the functional outcomes of NS RP using the IIEF scoring system.

A point of distinction between the NNS and NS cohorts is that the NNS group was significantly older and their tumor burden significantly larger (Supplementary Tables 2, 5). Traditional wisdom might indicate that an older group with higher tumor burden (receiving NNS surgery) would have impaired continence compared to a younger group with less tumor burden (receiving NS surgery). However, we found no such differences.

To establish a degree of homology with prior work, we also performed a subanalysis using surgeon-defined NS. Here, too, we found no difference in UI rates between either definition of NS and NNS surgery. We also performed a subanalysis using the term “successful NS,” but strayed away from defining success based on penile tumescence for intercourse [5]. Instead, we relied upon another clear, widely accepted scoring system—IIEF—to assess potency. In all of these subanalyses, NS did not influence the return or preservation of UC.

Such results are surprising because there is a preponderance of data supporting the NS approach. However, our study demonstrates a different approach to defining “NS,” which ultimately impacted how we assessed postoperative outcomes. Additionally, there is a growing body of work that questions the role of the NVB in explicitly innervating the urinary sphincters versus its more clear-cut role in innervating the penis and contributing to potency [26-29]. This is still an area of debate, as a recent publication suggested that the NS technique (and not NVB preservation) was paramount to UC preservation [30].

Strengths of this study include: long follow-up (up to 9 years), largely unchanged, single institution, and single senior surgeon.

On the other hand a corresponding criticism to our singlecenter status and geographic location would undoubtedly be having a small cohort size. However, the number of patients in our study is comparable in size to several studies [7]. Furthermore, even if significant differences in the postoperative UC of NS and NNS surgeries were seen with higher patient volumes, the clinical relevance of NS surgery would still be called into question.

In conclusion, in this study, we used the IIEF-EF scoring system to objectively measure the postoperative success of NS RP and found that NS RP did not improve postoperative UC. NS surgery conducted with the intent of improving postoperative UC is not necessarily evidence-based. Conservation of UC should not be the primary motivating factor in whether or not a patient and surgeon decide to pursue NS RP and should be highly questioned in the presence of preoperative ED.