Cancers | Free Full-Text | Assessing Trifecta and Pentafecta Success Rates between Robot-Assisted vs. Open Radical Cystectomy: A Propensity Score-Matched Analysis

Urothelial bladder cancer is the most frequent type of bladder cancer (BCa). BCa is frequently detected in older people and is closely related to smoking, but also to environmental factors and toxics [1]. BCa is the fifth most common cancer in Europe [2]. BCa is classified as non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). The standard of care for treating high-risk BCa is radical cystectomy (RC), with regional pelvic lymphadenectomy (PLND) preceded by neoadjuvant chemotherapy [3,4]. MIBC, even with optimal care, still presents with high morbidity and mortality [5]. There are major surgical risks associated with conducting extensive pelvic surgery and reconstructing the urinary system in an aged, comorbid population. A wide range of surgical treatments have made extensive use of minimally invasive surgical techniques. Using minimally invasive methods more frequently is one way to reduce surgical morbidity and accelerate recovery [6]. To reduce surgical morbidity, minimally invasive procedures, like robotic-assisted radical cystectomy (RARC), have been developed. Compared to open surgery, robotic-assisted surgery in urology has been proven to reduce blood loss, the requirement for transfusion, and the duration of the stay [7,8,9]. Although these advantages are commonly accepted, no studies have shown the significant impact of RARC compared to ORC regarding oncologic and long-term survival. The Razor study, which is a randomized phase 3 non-inferiority trial, did not find differences between RARC and ORC in 2-year progression free survival [10]. Concerns regarding RARC costs have also been reported [11]. The scientific community needs to finally establish the function of the robotic technique for the surgical treatment of bladder cancer because high-level evidence in favor of robotic RC remains scarce [12]. Several criteria have been proposed to assess RC quality in the past, evaluating oncological and perioperative outcomes [13]. Trifecta and pentafecta criteria are well established for partial nephrectomy (surgical margins status, functional preservation, and complications) [14] and radical prostatectomy (urinary continence, potency, cancer control, surgical margin status, and postoperative complications) [15]. Aziz et al. [16] proposed trifecta and pentafecta criteria composed of oncological and functional outcomes. In this study, we sought to determine whether RARC had a definite advantage over ORC using the trifecta and pentafecta criteria.

Between January 2017 and December 2022, 409 patients were treated with RC for BC; of these, 38 patients were excluded due to lack of follow-up data. In total, 371 patients were included in the study, 41 patients were treated with RARC, and 330 were treated with ORC. The mean operating times were 447 min and 356 min in the RARC and ORC groups, respectively. The median follow-up times were 10 (IQR: 9–12) months after RC. No differences were found in the pathologic stage between the two groups, with 61% (25/41) and 51% (169/330) being T2 in the RARC and ORC groups, respectively. No significant differences in histology were reported between the two groups. A statistically significant difference was observed in the UD type between the groups regarding orthotopic neobladder (RARC: 44% vs. ORC: 17%, p p p Table 1).

The primary endpoint was to assess differences in trifecta and pentafecta success rates between the ORC and RARC groups. The trifecta success rates were 63% (26/41) and 57% (188/330) for patients treated with RARC and ORC, respectively (p = 0.43). The pentafecta success rates were 32% (12/41) and 39% (128/330) of patients treated with RARC and ORC, respectively (p = 0.38). No statistically significant differences were found after PS matching in the trifecta and pentafecta success rates. The analyses for each variable of the trifecta and pentafecta before and after PS matching are reported in (Table 2). Before PS matching, there was a statistically significant difference in the treatment-free time ≤ 3 months after TURBT (RARC: 61% vs. ORC: 71%, p = 0.01) and in the absence of local recurrence within 12 months after RC (RARC: 85% vs. ORC: 71%, p = 0.01). After PS matching, only a statistically significant difference in the treatment-free time ≤ 3 months after TURBT was observed (p = 0.02). There were no statistically significant differences pre- and post-PS matching in negative STSMs (RARC: 98% vs. ORC: 96% p = 0.43), ≥16 lymph node count (RARC: 85% vs. ORC: 80%, p = 0.43), and the absence of major (Clavien–Dindo ≥ III) complication rates (RARC: 15% vs. ORC: 17%, p = 0.36) (Table 2).

Pre- and post-PS matching EBLs (RARC: 317 mL vs. ORC 622 mL, p = 0.01) and perioperative transfusion rates (RARC: 21% vs. ORC 38%, p = 0.01) were significantly lower, while no differences in terms of LOS (RARC: 16 vs. ORC: 15, p = 0.60) and 90-day hospital readmission rates (RARC: 20% vs. ORC: 24%, p = 0.88) were observed (Table 3).

Upon Kaplan–Meier analysis, no significant differences in OVS between the two cohorts were observed before (log rank = 0.32) or after PS matching (log rank = 0.26) (Figure 1).

Radical cystectomy remains the benchmark treatment for muscle-invasive bladder cancer. ORC has been refined over decades; therefore, the majority of urologists feel confident with this technique. However, RARC is becoming increasingly prevalent and accessible. RARC has been demonstrated to be technically feasible, with several RCTs indicating its potential [19,20,21,22,23,24,25]. Recent meta-analyses reported advantages in LOS, EBLs, and PBTs with RARC [26,27]. Of interest is the association between PBTs and worse oncological outcomes (higher recurrence rates and mortality), which is an important factor to take into account when choosing the optimal surgical approach [28]. ORC has shown a longer LOS and worse early health-related QoL outcomes compared to RARC at 5, 12, and 26 weeks [29]. No significant differences in terms of operative times between RARC with intracorporeal reconstruction (iRARC) and ORC were observed [27]. However, no clear advantages of reducing major complication rates and improving OVS and QoL were found in RARC, although the RCTs evaluating these outcomes did not assess survival outcomes [27]. Therefore, in such a complex scenario, reporting surgical outcomes correctly and precisely is pivotal to adequately compare the two approaches. To help to standardize outcomes in robotic surgery, Salomon et al. proposed the trifecta for radical prostatectomy in 2003 [30]. In 2015, Aziz et al. [16] (PROMETRICS group) introduced the concepts of trifecta and pentafecta to assess the quality and oncological efficacy of radical cystectomy [16,31]. In 2019, Cacciamani et al. [31] expanded upon this by proposing an RC-pentafecta, which includes the absence of ureteral diversion-related surgical complications. We tested the trifecta and pentafecta from the PROMETRICS group on both the RARC and ORC cohorts. Our study revealed no differences in trifecta (RARC: 67% vs. ORC: 57%, p = 0.43) and pentafecta (RARC: 32% vs. ORC: 39%, p = 0.38) success rates between the RARC and ORC cohorts. The trifecta and pentafecta helped us in assessing RC quality, but functional outcomes and QoL were not considered, which is something to consider in the future.

The rates of negative STSMs were similar between the two groups (RARC: 98% vs. ORC: 96%, p = 0.62). Negative STSMs are a critical outcome in oncologic surgery, being associated with metastatic progression, overall survival, and cancer-specific mortality [32]. In the literature, a positive STSM rate 33]. No significant differences in the lymph node count were observed (RARC: 85% vs. ORC: 80%, p = 0.43). After PSM analysis, no differences were found between the two cohorts. These rates are in line with previous studies on RARC vs. ORC [20,21,24,26].

No statistically significant differences were observed regarding the absence of major complications at 90 days, while the interval between the transurethral resection of bladder tumor and radical cystectomy was notably briefer among patients in the ORC group (RARC: 61% vs. ORC: 78%, p = 0.01). This discrepancy likely derived from the limited availability of robotic surgical slots at our institution. Additionally, the COVID-19 pandemic may have exacerbated this issue by reducing the number of robotic procedures performed, thereby impacting surgical waiting lists adversely [34,35].

After PS matching, RARC still demonstrated superior outcomes in terms of intraoperative EBLs and decreased rates of PBTs, yet no further significant disparities were identified. Notably, a reduction of over 50% in blood loss has been documented, consistent with previous studies [22,24,25,29].

Because RC is associated with significant morbidity [36], the use of minimal invasive approaches is promising to reduce perioperative complications and increase functional outcomes [37]. Recovery protocols have been proposed to reduce peri- and intraoperative complications through multidisciplinary efforts [38]. Enhanced recovery after surgery (ERAS) protocols aim to optimize recovery reducing perioperative complications, time to first bowel movement, and the length of hospital stay [39]. However, no significant differences were found in LOS (RARC: 16 days vs. ORC: 15 days, p = 0.53), which is in line with the results from the BORARC trial [21].

OVS rates at 12-month follow-up for RARC and ORC were 93% and 84% (p = 0.29), respectively, which is in line with the current literature. We observed no differences in OVS after PS matching and Kaplan–Meier survival analysis (log rank = 0.26). However, this study did not assess survival outcomes; therefore, a larger sample and longer follow-up times are needed. Interestingly, Brassetti et al. [37] in a retrospective study found a significant difference in OVS in patients achieving trifecta at 12 months, defined as urinary continence, recurrence-free status (RFS), and the absence of RARC-/ICUD-related severe complications (SCs) after iRARC, suggesting that trifecta could be used as a tool to decide which patients could benefit from a stricter follow-up. In general, OVS in the first years is commonly associated with bladder cancer, but with a longer follow-up time, deaths are associated with patients’ comorbidities or other diseases not related to bladder cancer [3].

Readmission rates were comparable between the two cohorts (RARC: 20% vs. ORC: 21%, p = 0.90), and similar outcomes were reported in previous studies [29]. The main causes of readmission in the first 90 days were infection, sepsis, and surgical wound issues. At 90 days, readmission rates were around 26%, of which 60% occurred in the first 30 days. Unfortunately, no clear benefits have been proven on the role of RARC in reducing readmission rates [27,40].

In our cohorts, UD assessment were performed extracorporeally, which could have reduced the benefits of a totally robotic procedure [37]. Nonetheless, a recent RCT between ORC and RARC with a totally intracorporeal urinary reconstruction only showed similar oncological outcomes, but a significant impact on perioperative outcomes [41].