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Salvage radical cystectomy after radiotherapy: A more complicated procedure?
14th Meeting of the EAU Section of Oncological Urology (ESOU)
Salvage radical cystectomy after radiotherapy: A more complicated procedure? P. Gontero, F. Soria, Turin (IT) Radical cystectomy (RC) is currently the gold standard treatment option for muscle invasive bladder cancer (MIBC) due to its undisputable oncological efficacy (1, 2). In spite of advances in surgical techniques and postoperative care, the procedure carries a significant morbidity. Recent series adopting a standardized methodology for reporting of complications observed that one out of 2 patients experienced at least a single complication within 3 months from surgery which was categorized as severe in 15% and lethal in 3% of cases (3, 4). In some instances, RC is required in a salvage setting after previous radiotherapy (RT). While the term salvage RC (sRC) in the majority of cases refers to failure of bladder sparing approaches to treat MIBC, other malignant diseases, namely gynaecological and colorectal cancers, usually treated with a multimodal approach that includes RT, may subsequently need sRC for disease recurrence or severe radiation toxicity to the bladder (5). Bladder cancer arising after previous radiation treatment for prostate cancer is another emerging context of sRC, potentially due to the enhanced risk of radiation induced secondary bladder malignancy (6). Since BCa is mainly a disease of the elderly, with a median age at diagnosis of 73 years and the majority of new diagnoses occurring in the decade between 75 and 84 years, a non-negligible rate of patients undergoing RC have been previously irradiated (7). RT could be delivered from an external source or internally by means of brachytherapy. It is known to induce severe tissue damages that extend beyond the organ of interest to the surrounding organs by carrying a desmoplastic reaction that makes difficult the identification and dissection of surgical planes. Moreover, tissue ischemia resulting from RT could lead to more vulnerable intestinal tissue, with higher risk of perforation, prolonged ileus, diarrhoea, delayed wound healing and increased infection rates (8) These modifications led to the perception of a more challenging and morbid surgery after RT. This perception was corroborated by historical series reporting perioperative complications and perioperative mortality rates ranging from 44% to 66% and from 15% to 33%, respectively (5). Despite these evidences, perioperative outcomes of RC after RT remain mostly unknown. More contemporary series comparing irradiated and non-irradiated patients provided conflicting results. Eisenberg et al. (9) reviewed the complication rate within 90 days of surgery in 148 patients treated with RC at a single institution who previously received 60 Gy or greater pelvic RT. Overall, 9 patients (6.1%) died during the first 90 days due to surgical procedure; no intraoperative deaths were reported. Moreover, 114 of 148 patients (77%) experienced one or more early complications with a mean of 2.9 complications per patients. Of these, 32.4% (48 of 148) experienced high grade complications, according to Clavien-Dindo classification system. Al Hussein Al Awamlh et al. (10) compared the perioperative outcomes of irradiated and nonirradiated patients undergoing robotic-assisted radical cystectomy (RARC). Of 252 patients enrolled in the study, 48 had a history of prior pelvic irradiation. No differences were seen between groups. Interestingly, 54% of patients in both groups experienced complications; of these, 24% and 21% were graded as major complications in irradiated and non-irradiated patients, respectively. We recently aimed to clarify the morbidity rate of RC after RT in a large, multicenter series of 682 patients from 28 high volume centers using a standardized methodology of reporting of complications. All patients had a previous history of RT for urological or non-urological cancer Eur Urol Suppl 2017; 16(2):90
14th Meeting of the EAU Section of Oncological Urology (ESOU) and subsequently underwent RC. Complications were categorized according to type (medical and surgical) and time of onset (early, intermediate and late). Complications were graded according to the Clavien-Dindo classification (11). During follow up, three-quarters of the patients experienced at least one complication after RT, half of them had a major complication (Clavien grade ≥ 3) and a non-negligible rate of patients experienced a fatal complication. In the majority of the cases complications were surgery-related. When analysing the influence of different radiation regimens on RC outcomes, RT for bladder cancer increased the risk of any complication after secondary RC compared to patients previously irradiated for prostate cancer. RC after previous RT carries a high major complication rate that, contrary to previous reports, dramatically outweighs that reported in RT naïve RCs. Patients undergoing such procedure should be counselled accordingly. References 1. Hautmann RE, Gschwend JE, de Petriconi RC et al: Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 2006; 176-486 2. Witjes JA, Compérat E, Cowan NC, De Santis M, Gakis G, Lebret T, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 2014; 65:778–92. 3. Shabsigh A, Korets R, Vora KC et al: Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55:164. 4. Novara G, De Marco V, Aragona M et al: Complications and mortality after radical cystectomy for bladder transitional cell cancer. J Urol 2009; 182:914. 5. Ramani VA, Maddineni SB, Grey BR et al: Differential complication rates following radical cystectomy in the irradiated and non irradiated pelvis. Eur Urol 2010; 57:105863. 6. Yee DS, Shariat SF, Lowrance WT et al. Impact of previous radiotherapy for prostate cancer on clinical outcomes of patients with bladder cancer. J Urol. 2010 May;183(5):1751-6 7. Galsky MD. How I treat bladder cancer in elderly patients. J Geriatr Oncol. 2015;6(1):1–7. 8. Nieuwenhuijzen JA, Horenblas S, Meinhardt W, van Tinteren H, Moonen LMF. Salvage cystectomy after failure of interstitial radiotherapy and external beam radiotherapy for bladder cancer. BJU Int 2004; 94:793–7. 9. Eisenberg MS, Dorin RP, Bartsch G et al. Early complications of cystectomy after high dose pelvic radiation. 2010; 184:2264-69. 10. Al Hussein Al Awamlh B, Nguyen DP, Otto B et al. The safety of robot-assisted cystectomy in patients with previous history of pelvic irradiation. BJU Int 2016; 118:437443. 11. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240:205–13.
Eur Urol Suppl 2017; 16(2):91
Salvage radical cystectomy after radiotherapy: A more complicated procedure? P. Gontero, F. Soria, Turin (IT) Radical cystectomy (RC) is currently the gold standard treatment option for muscle invasive bladder cancer (MIBC) due to its undisputable oncological efficacy (1, 2). In spite of advances in surgical techniques and postoperative care, the procedure carries a significant morbidity. Recent series adopting a standardized methodology for reporting of complications observed that one out of 2 patients experienced at least a single complication within 3 months from surgery which was categorized as severe in 15% and lethal in 3% of cases (3, 4). In some instances, RC is required in a salvage setting after previous radiotherapy (RT). While the term salvage RC (sRC) in the majority of cases refers to failure of bladder sparing approaches to treat MIBC, other malignant diseases, namely gynaecological and colorectal cancers, usually treated with a multimodal approach that includes RT, may subsequently need sRC for disease recurrence or severe radiation toxicity to the bladder (5). Bladder cancer arising after previous radiation treatment for prostate cancer is another emerging context of sRC, potentially due to the enhanced risk of radiation induced secondary bladder malignancy (6). Since BCa is mainly a disease of the elderly, with a median age at diagnosis of 73 years and the majority of new diagnoses occurring in the decade between 75 and 84 years, a non-negligible rate of patients undergoing RC have been previously irradiated (7). RT could be delivered from an external source or internally by means of brachytherapy. It is known to induce severe tissue damages that extend beyond the organ of interest to the surrounding organs by carrying a desmoplastic reaction that makes difficult the identification and dissection of surgical planes. Moreover, tissue ischemia resulting from RT could lead to more vulnerable intestinal tissue, with higher risk of perforation, prolonged ileus, diarrhoea, delayed wound healing and increased infection rates (8) These modifications led to the perception of a more challenging and morbid surgery after RT. This perception was corroborated by historical series reporting perioperative complications and perioperative mortality rates ranging from 44% to 66% and from 15% to 33%, respectively (5). Despite these evidences, perioperative outcomes of RC after RT remain mostly unknown. More contemporary series comparing irradiated and non-irradiated patients provided conflicting results. Eisenberg et al. (9) reviewed the complication rate within 90 days of surgery in 148 patients treated with RC at a single institution who previously received 60 Gy or greater pelvic RT. Overall, 9 patients (6.1%) died during the first 90 days due to surgical procedure; no intraoperative deaths were reported. Moreover, 114 of 148 patients (77%) experienced one or more early complications with a mean of 2.9 complications per patients. Of these, 32.4% (48 of 148) experienced high grade complications, according to Clavien-Dindo classification system. Al Hussein Al Awamlh et al. (10) compared the perioperative outcomes of irradiated and nonirradiated patients undergoing robotic-assisted radical cystectomy (RARC). Of 252 patients enrolled in the study, 48 had a history of prior pelvic irradiation. No differences were seen between groups. Interestingly, 54% of patients in both groups experienced complications; of these, 24% and 21% were graded as major complications in irradiated and non-irradiated patients, respectively. We recently aimed to clarify the morbidity rate of RC after RT in a large, multicenter series of 682 patients from 28 high volume centers using a standardized methodology of reporting of complications. All patients had a previous history of RT for urological or non-urological cancer Eur Urol Suppl 2017; 16(2):90
14th Meeting of the EAU Section of Oncological Urology (ESOU) and subsequently underwent RC. Complications were categorized according to type (medical and surgical) and time of onset (early, intermediate and late). Complications were graded according to the Clavien-Dindo classification (11). During follow up, three-quarters of the patients experienced at least one complication after RT, half of them had a major complication (Clavien grade ≥ 3) and a non-negligible rate of patients experienced a fatal complication. In the majority of the cases complications were surgery-related. When analysing the influence of different radiation regimens on RC outcomes, RT for bladder cancer increased the risk of any complication after secondary RC compared to patients previously irradiated for prostate cancer. RC after previous RT carries a high major complication rate that, contrary to previous reports, dramatically outweighs that reported in RT naïve RCs. Patients undergoing such procedure should be counselled accordingly. References 1. Hautmann RE, Gschwend JE, de Petriconi RC et al: Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 2006; 176-486 2. Witjes JA, Compérat E, Cowan NC, De Santis M, Gakis G, Lebret T, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 2014; 65:778–92. 3. Shabsigh A, Korets R, Vora KC et al: Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55:164. 4. Novara G, De Marco V, Aragona M et al: Complications and mortality after radical cystectomy for bladder transitional cell cancer. J Urol 2009; 182:914. 5. Ramani VA, Maddineni SB, Grey BR et al: Differential complication rates following radical cystectomy in the irradiated and non irradiated pelvis. Eur Urol 2010; 57:105863. 6. Yee DS, Shariat SF, Lowrance WT et al. Impact of previous radiotherapy for prostate cancer on clinical outcomes of patients with bladder cancer. J Urol. 2010 May;183(5):1751-6 7. Galsky MD. How I treat bladder cancer in elderly patients. J Geriatr Oncol. 2015;6(1):1–7. 8. Nieuwenhuijzen JA, Horenblas S, Meinhardt W, van Tinteren H, Moonen LMF. Salvage cystectomy after failure of interstitial radiotherapy and external beam radiotherapy for bladder cancer. BJU Int 2004; 94:793–7. 9. Eisenberg MS, Dorin RP, Bartsch G et al. Early complications of cystectomy after high dose pelvic radiation. 2010; 184:2264-69. 10. Al Hussein Al Awamlh B, Nguyen DP, Otto B et al. The safety of robot-assisted cystectomy in patients with previous history of pelvic irradiation. BJU Int 2016; 118:437443. 11. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240:205–13.
Eur Urol Suppl 2017; 16(2):91