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Relapses after Robot-Assisted Radical Cystectomy
By: Ahmed S. Elsayed, MD; Khurshid A. Guru, MD | Posted on: 29 Jan 2021
If surgeons adhere to key oncologic principles, robot-assisted radical cystectomy (RARC) provides equal oncologic results compared to open radical cystectomy (ORC) based on 5-year and 10-year studies. 1 Concerns regarding relapses have risen since a higher incidence of peritoneal carcinomatosis (21% vs 8%) and extrapelvic lymph node recurrence (23% vs 15%) after RARC when compared to ORC was reported. Various explanations including methodological and statistical concerns have been reported. 2
Several hypotheses have been proposed to explain the potential higher incidence of recurrences after RARC compared to ORC. The lack of tactile feedback may increase the risk of positive soft tissue surgical margins (PSTSM), especially in locally advanced disease, and that potentially may lead to a higher incidence of local recurrence. Carbon dioxide pneumoperitoneum deployed in minimally invasive surgery has been considered to inhibit peritoneal immune response against malignant urothelial cells leading to recurrence in the pelvis and at port sites, although never validated.
Table 1. Summary of recurrences rates and patterns after radical cystectomy despite surgical approach.
| Present | Venkatramani et al 4 | Bochner et al 3 | Collins et a l5 | |
|---|---|---|---|---|
| Year | 2020 | 2020 | 2018 | 2017 |
| Type of study | Retro | RCT | RCT | Retro |
| No. patients | 2107 | 152 vs 150 | 58 vs 60 | 717 |
| Surgical approach | RARC | ORC vs RARC | ORC vs RARC | RARC |
| Any followup (months) | 26 | 36 | 59 | 31 |
| % Urothelial carcinoma | 77 | 76 vs 82 | 95 vs 95 | 95 |
| % pT3 or greater | 37 | 32 vs 31 | 33 vs 28 | 33 |
| % Positive disease margins | 6 | 5 vs 6 | 5 vs 3 | 4.8 |
| % Pathological node positive disease | 20 | 16 vs 23 | 16 vs 17 | 18 |
| No. RFS | 66 at 5 yrs | 65 vs 68 at 3 yrs | NR | 75 at 2 yrs |
| No. LRFS | 84 at 5 yrs | NR | NR | NR |
| No. DMFS | 74 at 5 yrs | NR | NR | NR |
| % Any recurrence | 25 | 26 vs 26 | 43 vs 33 | 25 |
| % Local recurrence | 11 | 3 vs 4 | NR | 11 |
| Most common site of local recurrence | Pelvis | Cystectomy bed | Pelvic soft tissue | Pelvic lymph nodes |
| % Distant metastases | 18 | 23 vs 22 | 18 | |
| Most common site of distant metastases | Lungs and extra-pelvic lymph nodes | Extra-pelvic lymph nodes and bone vs bone | Extra-pelvic lymph nodes | Extra-pelvic lymph nodes |
| % Peritoneal carcinomatosis | 1.2 | 0.7 vs 1.3 | 3 vs 3 | 0.7 |
| % Abdominal wall/port-site metastases | 1.2 | 0.7 vs 0 | 0 vs 8 | 0.6 |
| % Extrapelvic lymph nodes | 5 | 6 vs 6 | 17 vs 8 | 7 |
To determine the relapse rates and patterns after RARC, the International Robotic Cystectomy Consortium (IRCC) performed a retrospective review of the prospectively maintained database (3,000+ patients among 28 institutions from 14 countries). A total of 2,107 eligible patients were analyzed for disease relapse following RARC, and 521 patients (25%) relapsed. Local recurrences were observed in 241 (11%) and distant metastasis occurred in 382 (18%) patients. Early oncologic failure (within 3 months) was seen in 4%. The median time to disease relapse, local recurrence and distant metastases was 8 months for all categories. The most common site for local recurrence was the pelvis (5%) while the most common sites for distant metastasis were the lungs (6%) and extrapelvic lymph nodes (5%). Abdominal wall/port-site metastases were observed in 25 patients (1.2%), and peritoneal carcinomatosis was observed in 26 patients (1.2%). Five-year relapse-free survival (RFS), local recurrence-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) were 66%, 84%, 74% and 60% respectively.
On final report preoperative hydronephrosis was associated with poor RFS, LRFS and DMFS. Perioperative blood transfusion was associated with RFS and DMFS. Meanwhile, age, ileal conduit urinary diversion and ICU stay were associated with worse OS. Pathological T3 or greater and node positive disease were associated with worse RFS, LRFS and OS. PSTSM was associated with worse LRFS and OS.
Several randomized controlled trials (RCTs) have shown similar RFS (up to 5 years) between ORC and RARC. 3,4 Similar findings were recently reported by the Controlled Three-arm Trial of Open, Robotic, and Laparoscopic Radical Cystectomy (CORAL) trial showing similar RFS between ORC, laparoscopic RC and RARC. Large retrospective studies found that RARC had a similar oncologic outcome compared to large ORC series based on historic data. 1 The current study shows similar RFS in comparison to previous RARC and ORC series (see table).
Bochner et al showed nonstatistically significant differences between ORC and RARC analyzing local and abdominal wall recurrences separately. 3 However, when the pelvic and abdominal recurrences were combined into a single group representing local/regional recurrence, the ORC group showed significantly less local/regional recurrence compared to RARC (p=0.035). Intra-abdominal recurrences have been attributed to the lack of tactile feedback and subsequent inadequate cancer control, especially for locally advanced tumors. We did not note an unreasonably high rate of local or abdominal recurrences in our series.
While intracorporeal urinary diversion (ICUD) has been increasingly adopted, an extracorporeal approach has been used for all patients in previously published RCTs comparing ORC and RARC. Therefore, the effect of the diversion approach was not examined. 3,4 Our study shows no oncologic differences between the open and ICUD approaches. The iROC trial, which is an RCT comparing RARC with ICUD to ORC, is currently recruiting and may provide more robust evidence regarding the effect of diversion approach.
The stage of disease and adverse features remains the main predictor of relapse and survival following RARC. Like any other surgical procedure, technique and strictly adhering to oncologic principles hold the keys to best chances towards success after RARC.
- Hussein AA, Elsayed AS, Aldhaam NA et al. Ten-year oncologic outcomes following robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. J Urol 2019; 202: 927.
- Pourmalek F, Abdi H and Black PC: Re: Daniel P. Nguyen, Bashir Al Hussein Al Awamlh, Xian Wu, et al. Recurrence patterns after open and robot-assisted radical cystectomy for bladder cancer. Eur Urol 2015;68:399–405. Eur Urol 2016; 69: e35.
- Bochner BH, Dalbagni G, Marzouk KH et al: Randomized trial comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: oncologic outcomes. Eur Urol 2018; 74: 465.
- Venkatramani V, Reis IM, Castle EP et al: Predictors of recurrence, and progression-free and overall survival following open versus robotic radical cystectomy: analysis from the RAZOR Trial with a 3-year followup. J Urol 2020; 203: 522.
- Collins JW, Hosseini A, Adding C et al: Early recurrence patterns following totally intracorporeal robot-assisted radical cystectomy: results from the EAU Robotic Urology Section (ERUS) Scientific Working Group. Eur Urol 2017; 71: 723.