Long-term Outcomes of Prostate Capsule-Sparing and Nerve-Sparing Radical Cystectomy With Neobladder: A Propensity Score-Matched Comparison

Study Population

Between June 2004 and December 2021, 648 men underwent RC plus urinary diversion at Jinhua Hospital Afffliated to Zhejiang University School of Medicine. Of these, 216 patients received an orthotopic neobladder. Among them, 59 patients underwent non-NS surgery preoperatively due to sexual inactivity, erectile dysfunction, or no requirement for preserving sexual function. Three patients had incomplete medical records, and 9 were followed for less than 12 months. Consequently, 145 patients were included in the study. Patients who were more sexually active before surgery and expressed a strong desire to preserve sexual function were selected for function-preserving cystectomy (PCS or NS). PCS was offered only to those who met the following inclusion criteria: (1) patients requesting preservation of sexual function and providing fully informed consent; (2) bladder cancer stages cT1–T3 N0 M0, with no tumor at the bladder neck confirmed by cystoscopy or biopsy; (3) normal prostate-specific antigen (PSA) levels (<4 ng/dL), transrectal ultrasound, and magnetic resonance imaging results; in cases with a suspicious prostate nodule, a negative biopsy result was required.

Surgical Techniques

Covariates and Outcome Evaluation

Tumors were staged and classified according to the 2002 TNM system. The postoperative follow-up schedule was structured as follows: patients were seen every 3 months during the first year, every 6 months during the second year, and annually thereafter. Follow-up evaluations included physical examinations, routine blood tests, blood biochemistry analyses, PSA level assessments, routine urine tests, chest x-rays, urinary ultrasounds, and computed tomography (CT) scans. Additionally, CT urography and cystoscopy were performed as needed. The primary endpoint of the study was overall survival (OS) time. Follow-up time was defined as the duration from the postoperative period to either the patient’s death or the last follow-up visit.

Functional Assessment

Functional assessment was conducted across 3 domains: urinary control (UC), sexual function, and complications. This assessment was carried out by a team of physicians and nurses not involved in the surgery, using either direct questioning during follow-up visits or by telephone. (1) Follow-up of UC function involved querying patients about their daily use of routine pads at 3, 6, and 12 months postoperatively, allowing for a one-week window before and after these time points. Urinary incontinence was defined as the daily use of one or more pads, while recovery of UC was defined as complete dryness, requiring no pads [12, 13, 20]. (2) For sexual function, the endpoint was defined as the best sexual performance, equivalent to preoperative levels, observed at any time. Preoperative questions about sexual function included topics on fertility, sexual activities (such as masturbation, foreplay, and intercourse), and erectile dysfunction. Postoperatively, at 6 months, questions focused on sexual activity and erectile function, comparing them to preoperative levels, and were recorded accordingly. (3) Complications were analyzed based on the Clavien classification [21] and included voiding obstruction, urinary tract infection, rehospitalization rates, and other complications requiring therapeutic intervention.

Statistical Analysis

Statistical analyses and PSM were conducted using IBM SPSS Statistics ver. 27.0 (IBM Co., Armonk, NY, USA). Continuous variables are presented as mean±standard deviation and were compared using an independent t-test. Categorical variables are reported as absolute numbers and percentages and were compared using the χ² test or Fisher exact test. Metastasis-free probability, cancer-specific survival (CSS), and OS were calculated using the Kaplan-Meier method, and differences in survival curves between the 2 groups were assessed using the log-rank test. A P-value of less than 0.05 was considered statistically significant.

A multivariate logistic regression model was used to calculate a propensity score for each patient. This score included variables such as age, body mass index (BMI), smoking history, American Society of Anesthesiologists (ASA) physical status (PS) classification grade, surgical approach, pathologic T stage, lymph node metastasis (N+), presence of carcinoma in situ, postoperative grade, positive surgical margin, follow-up duration, and the use of neoadjuvant and adjuvant therapy. The PSM ratio was established at 1:1, with a matching tolerance of 0.02 between the 2 groups.

Clinical Baseline Characteristics

Table 1 presents the characteristics of the PCS and NS groups before and after matching. A total of 96 patients were successfully matched, with 48 in each of the PCS and NS groups. The groups were comparable in terms of age, BMI, smoking history, ASA PS classification grade, surgical approach, pathologic T stage, lymph node metastasis (N+), presence of carcinoma in situ, postoperative grade, prostate cancer, positive surgical margin, follow-up duration, and the use of neoadjuvant and adjuvant therapy, with no significant differences observed (P>0.05).

Table 1

Characteristics of the PCS and NS groups before and after matching

Oncological Outcomes

The median follow-up periods were 155 months for the PCS group and 122 months for the NS group. Cumulative survival estimates indicated a metastasis-free probability of 88.2% at both 5 and 10 years for the PCS group, compared to 71.5% in the NS group (P=0.206) (Fig. 1A). For CSS, the rates were 90.2% at both 5 and 10 years in the PCS group, whereas in the NS group, the rates were 80.9% at 5 years and 68.4% at 10 years (P=0.091) (Fig. 1B). OS rates were 87.7% at 5 years and 41.8% at 10 years in the PCS group, compared to 59.9% at 5 years and 41.0% at 10 years in the NS group (P=0.208) (Fig. 1C). Overall, no significant differences were observed between the 2 groups (P>0.05) (Fig. 1).

Fig. 1

Metastasis-free probability (A), cancer-specific survival (CSS; B), overall survival (OS; C). Kaplan-Meier curves of oncological endpoints between the 2 groups. The differences were not statistically significant (P>0.05). PCS, prostate capsule-sparing; NS, nerve-sparing.

Functional Recovery

Table 2 shows the results of postoperative functional recovery in the PCS and NS groups. Functional follow-up exceeding 12 months postoperatively was available for all patients. The rates of complete daytime UC (0 pads) at 3, 6, and 12 months postoperatively were 72.9%, 91.7%, and 97.9% in the PCS group, and 47.9%, 79.2%, and 91.7% in the NS group, respectively (P=0.012, P=0.083, and P=0.362). Notably, daytime UC was more common in the PCS group than in the NS group (P< 0.05) at 3 months and was comparable at 6 and 12 months. The rate of complete nocturnal UC (0 pads) at 3, 6, and 12 months postoperatively was 54.2%, 85.4%, and 95.8% in the PCS group and 31.3%, 60.4%, and 83.3% in the NS group, respectively (P=0.023, P=0.006, and P=0.091). It was significantly higher in the PCS group than in the NS group (P<0.05) during the early postoperative period (3 and 6 months) and similar at 12 months. Recovery to preoperative erectile function levels was achieved in 30 (62.5%) and 11 patients (22.9%) in the PCS and NS groups, respectively, with a significantly higher rate in the PCS group than in the NS group (χ²=15.369, P<0.001).

Table 2

Results of postoperative functional recovery in the PCS and NS groups after matching

Complications

Table 3 presents postoperative complications in the PCS and NS groups. During the 30-day postoperative period, Clavien-Dindo Classification grade ≥III complications were recorded in 2 patients in the PCS group (1 case each of incisional infected fissure and intestinal obstruction) and 4 patients in the NS group (1 case each of incisional infected fissure, intestinal obstruction, intestinal fistula, and rectourethral fistula) (P=0.667). Eight patients in the PCS group and 1 patient in the NS group developed prostatitis/epididymitis (P=0.031); all cases were resolved after re-treatment. Complications such as urinary tract infections (pyelonephritis), adhesive bowel obstruction, and skin abscesses necessitated re-hospitalization. In the PCS group, 3 patients experienced loss of bladder function (high capacity and no contractility) at 11, 9, and 14 years postsurgery, respectively. These patients had either U-shaped or W-shaped ileal neobladders. The latter case was also complicated by multiple bladder stones, requiring surgical interventions such as cystostomy. Additionally, a patient with a sigmoidal colon U-type neobladder developed bladder stones 3 times within 5 years postsurgery, each instance requiring lithotripsy.

Table 3

Postoperative complications in the PCS and NS groups after matching

Tumor Recurrence and Survival

Regarding tumor recurrence and survival, in 2004, Botto et al. [25] reported that the incidence of distant metastasis was 30% in patients undergoing PCS. Another study demonstrated that the 5-year OS and CSS of patients undergoing NS total cystectomy was 71%–86.7% and 64%–86.7%, respectively [10]. Furthermore, the 5-year OS of prostate-preserving versus nonpreserving surgery was comparable (70.6% and 74.2%, respectively) [7]. Importantly, CSS rates for seminal vesicle prostate-preserving versus nonpreserving procedures were similar (73.41% and 80.65%, respectively) [26]. The median follow-up time of patients undergoing PCS and NS in this study was 155 and 122 months, respectively. The metastasis-free probability was 88.2% in the PCS group and 71.5% in the NS group, whilst the CSS rates were 90.2% and 90.2% and 80.9% and 68.4% at 5 and 10 years postsurgery, respectively. Meanwhile, the 5- and 10-year OS rates were 87.7% and 41.8% in the PCS group and 59.9% and 41.0% in the NS group, respectively. Taken together, these results indicate comparability between the 2 groups (P>0.05), implying that the choice of surgical technique did not significantly affect oncological outcomes.

Postoperative Function

In terms of UC and sexual function, the quality of life associated with neobladder reconstruction was significantly higher compared to other urinary diversion modalities [20]. Earlier studies [6, 7, 10–12] have established that, in patients undergoing NS procedures, the daytime UC rate ranges between 77% and 89.5%, while the nocturnal UC rate ranges from 54% to 88.9%. In contrast, in patients undergoing PCS, the daytime UC rate ranges between 94.4% and 100%, whereas the nocturnal UC rate is 70.2%–96%. Furthermore, He et al. [22] documented that at 3, 6, and 12 months postoperatively, the daytime UC rates were 34.1%, 66.7%, and 90% in the NS group, respectively, while the nocturnal UC rates were 27.3%, 57.1%, and 82.5%. Conversely, in the PCS group, the UC rates were 80%, 94.7%, and 92.9% during daytime and 75%, 94.7%, and 92.9% during nighttime, respectively. Additionally, Wang et al. [27] noted that the UC rates were 36.8%, 52.6%, and 94.7% during daytime and 5.3%, 21.1%, and 57.9% during nighttime in the NS (interfascial) group, respectively. Simultaneously, the daytime UC rates were 76.9%, 84.6%, and 91.7% in the NS (intrafascial) group, whereas the nocturnal UC rates were 46.2%, 58.3%, and 66.7%, respectively. Erectile function recovered in between 28.6% and 86.1% of patients in the NS group [7, 25–27] and in 50%–91.6% of patients in the PCS group [7, 9, 10]. Consequently, we posit that there is no universal consensus on a standardized measure for postoperative UC in the literature. Indeed, different studies employed various forms of questionnaires and urinary pad tests. For example, UC was defined as the use of a maximum of one pad per day or night or as a criterion based solely on the subjective report of patients. This results in the inability to objectively compare postoperative UC. The questionnaire employed included the widely recognized complete UC and voiding pattern questionnaire, wherein UC was defined as the non-use of pads (0 pads) by the patient [12, 13, 20]. It is worthwhile emphasizing that the complete UC rate at 3, 6, and 12 months postoperatively was significantly higher in the PCS group compared to the NS group (P<0.05) during the early postoperative period (3 and 6 months) and was comparable by 12 months postoperatively. Regarding sexual function recovery, 62.5% of patients undergoing PCS returned to preoperative levels, compared with 22.9% of those undergoing NS, highlighting the superiority of PCS over NS.

In this study, the incidence of postoperative complications was higher in the PCS group than in the NS group. Further analysis revealed that patients in the PCS group were at a greater risk of developing complications due to bladder neck obstruction.

Dysuria (requiring intermittent clean catheterization) within 6 months after surgery was more common in the PCS group. A total of 8.3% of patients in the PCS group developed bladder neck obstruction (including recurrent prostatic hyperplasia leading to dysuria) requiring surgical intervention. Additionally, 16.7% of patients in this group developed prostatitis or epididymitis. These complications may be attributed to factors such as the type and morphology of the bowel materials used to construct the neobladder. Given that all these complications occurred in the PCS group, it suggests that the PCS technique might be more prone to occult vesicourethral obstruction. This underscores the importance of long-term follow-up for patients who undergo PCS.

Limitations of This Study

This study provided an empirical summary based on a large patient cohort, reporting oncological and functional outcomes as well as complications associated with the PCS and NS techniques. However, all patients undergoing RC were selected from a single center, which could introduce selection bias. Additionally, while PSM was employed to mitigate imbalances in prognostic factors between treatment groups, a randomized controlled trial remains the gold standard for eliminating biases. Surgical outcomes are also significantly influenced by the skills and experience of the operator. In this case, all interventions were performed by or under the supervision of a senior chief physician (Zhu). The primary objective of this study was to report the oncological and functional outcomes of 2 different NS radical procedures.