SIU 2022 Updates Muscle-invasive bladder cancer in elder patient

CONGRESS & MEETING HIGHLIGHT

Carlo Giulioni

Department of Urology, Polytechnic University of Marche Region, Umberto I Hospital "Ospedali Riuniti", Ancona, Italy.

RADIOTHERAPY IN GREAT ELDERLY BLADDER CANCER: EXCLUSIVE OR TRIMODALITY TREATMENT?

Trimodality treatment is determined by maximal debulking transurethral resection of bladder tumour (TURBT) Combined with radiotherapy (RT) and platinum-based chemotherapy (CT). All cases are discussed at a multidisciplinary urologic tumour board and are dedicated to Highly selected patients, corresponding to 10-15% of current radical cystectomy patients (1). There are several criteria to consider in patient selection: • Radicality of TURBT • Tumor stage: negative lymph nodes are required • Hydronephrosis: significantly increased risk of distant metastasis • Multifocality and CIS are considered exclusion criteria • Good bladder function l Finality: to preserve normal function of the bladder • Highly motivated patients: patients must be aware of all options and agree with the possibility of salvage cystectomy • Discussion at multidisciplinary urologic tumour board.

Therefore, the ideal patients have T2 MIBC, with no hydronephrosis nor CIS, TURBT was visibly complete, the tumour was unifocal, with a necessary good bladder function and capacity. In a retrospective analysis of 475 patients with Т2-T4a

MIBC treated at the Massachusetts General Hospital with transurethral resection of bladder tumour followed by concurrent CT-RT, rates of CR improved from 66% to 88% and 5-yr disease-specific survival from 60% to 84% over treatment eras, with the 5-yr risk of salvage radical cystectomy rate decreasing from 42% to 16% (2). According to the evidence, TMT is mini-invasive therapy with low morbidity (sexual, urinary), leaving an intact bladder and guaranteeing satisfactory oncologic results. In an editorial commentary regarding stereotaxic radiotherapy (SBRT) (3), it targeting macroscopic bladder tumours could differ from the conventional palliative treatment of the whole bladder in three critical ways: • The treatment course is shortened; • The target volume is reduced and the daily dose is typically hypofractionated. • The intent is the symptoms (and tumour growth) management minimizing bowel and urinary toxicities, especially reducing OTT treatment and augmenting patients' compliance to RT.

In summary, the TMT approach might be considered a valid and feasible option in fit patients who refuse radical cystectomy (80% intact-bladder disease-free survival at 5 years). Patients' selection and a multidisciplinary discussion remain fundamental elements for proposing every approach in bladder cancer, even for elderly patients who are optimal candidates for TMT or palliative RT.

RADICAL CYSTECTOMY IN ELDERLY PATIENTS

Bladder cancer is a potential killer of the elderly, as cancerspecific mortality was higher in older individuals than in their younger counterparts (4). In pre-treatment decisionmaking, frailty is a determining factor as it correlates with mortality and side effects of cancer treatment and is more important than chronological age. According to the EAU guidelines, the decision on bladder-sparing treatment or radical cystectomy in older / frail patients with invasive bladder cancer must consider tumour stage and frailty (5). Therefore, one of the decision-making points is whether our approach has palliative or curative intent. Although an endoscopic procedure alone is not recommendable, performing a complete TURBT in the elderly is essential, as it may be curative in selected cases, cystectomy may not be feasible / refused, bladder sparing is more effective if no / low residual volume and re-tur may add morbidity. Partial cystectomy is a less challenging alternative for the elderly patient, although this procedure is contraindicated in the case of positive pelvic lymph nodes, prior history of urothelial carcinoma and ureteral reimplantation (6). Some factors can be relevant to improve partial cystectomy outcomes: • N-acetyl cysteine: Reduction on PSM & local recurrence. • PLND: CSM reduced from 40% to 30% when PLND was performed. • Advance in technology for positive margins rate: approximately 19% of PSM, no difference between robotic, lap. and open partial cystectomy.

Afterwards, the literature does not indicate a preference for radical cystectomy in the elderly. In a series of 34 elderly patients who underwent radical cystectomy and ureterocutaneostomy derivation, complications of grade III or greater, according to the Clavien-Dindo classification, were in about 5% of cases. There are no studies with large sample sizes on minimally invasive radical cystectomy in elderly patients, although they are promising. Yanagihara et al. reported a non-significant major postoperative complication rate compared to young patients, with similar outcomes for Cancer-specific survival and Recurrence Free Survival (7). Moreover, no case series regarding robot-assisted radical cystectomy was published, although the UAE guidelines recommend informing the patient about the pros and cons of this procedure (5). Nevertheless, regardless of the choice of surgical technique, current literature confirms that outcomes of cystectomy are better in centres performing over 20 surgeries per year. Therefore, elderly patients should be recommended to undergo cystectomy in high-volume centres, both for RARC and ORC. In summary, elderly patients with BC are more likely to die of bladder cancer than their younger counterparts and should not be denied RC just because of age/comorbidities. Nonetheless, these are fundamental determinants of postoperative morbidity and mortality.

URINARY DERIVATION IN THE ELDERLY PATIENT

Radical cystectomy with urinary derivation is the most complex surgical procedure in the urological field, with postoperative surgical morbidity up to 20 years after surgery. The type of urinary derivation is the most impacting factor on postoperative morbidity and quality of life in these patients (8). In a retrospective review of 117 patients over 80 years, there is a reduced probability of receiving continent derivation compared to young people (3% vs 40%), with a higher rate of entering the ICU (4% vs 11%) (9). Age> 80 years is often considered the threshold after which neobladder reconstruction is not recommendable, although in carefully selected elderly patients, all other forms of wet and dry urinary diversions, including orthotopic bladder substitutions, are possible. However, according to Tan et al., age is an independent predictor of high-grade complications beyond previous abdominal surgery, an ASA score> 2, and intraoperative blood loss (10). Then there are the late complications depending on the position and length of the segment intestinal used for urinary diversion. Bricker's Ileal Conduit is the preferred choice in patients with neurological and psychiatric disease, limited life expectancy, renal or hepatic failure, cancer extended to prostatic urethra/bladder neck, or complicated urethral stricture. Furthermore, due to the shorter contact time of urine with the intestinal mucosa, metabolic complications in patients with ileal duct are less frequent than in patients

with an orthotopic neobladder. Nevertheless, early (such as gastrointestinal or uretero-ileal anastomosis dehiscence) or late (such as bowel, renal, stomal complication or urolithiasis) may occur in approximately 30% of patients (11). Cutaneous ureterostomy may be equally valid in high-risk patients with previous intestinal surgery or radiotherapy aiming for an oncological debulking strategy or a palliative intent. According to a retrospective study comparing the outcomes of urinary diversions, UCS with a single stoma can represent a valid alternative to IC in elderly patients with relevant comorbidities, reducing peri-operative complications without significant impairment of quality of life (12). In conclusion, a radical cystectomy may be proposed for the older adult (> 75-80 yo), and several urinary diversions can be offered in the well selected patients, with acceptable complication rates and overall survival.

REFERENCES

1. Mathieu R, Lucca I, Klatte T, et al. Trimodal therapy for invasive bladder cancer: is it really equal to radical cystectomy? Curr Opin Urol. 2015; 25(5):476-82. 2. Giacalone NJ, Shipley WU, Clayman RH, et al. Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience. Eur Urol. 2017; 71(6):952-960. 3. Jereczek-Fossa BA, Marvaso G. Palliative radiation therapy in bladder cancer: a matter of dose, techniques and patients' selection. Ann Palliat Med. 2019; 8(5):786-789. 4. Lughezzani G, Sun M, Shariat SF, et al. A population-based competing-risks analysis of the survival of patients treated with radical cystectomy for bladder cancer. Cancer. 2011; 117(1):103-9. 5. EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022. ISBN 978-94-92671-16-5 6. Ma B, Li H, Zhang C, et al. Lymphovascular invasion, ureteral reimplantation and prior history of urothelial carcinoma are associated with poor prognosis after partial cystectomy for muscle-invasive bladder cancer with negative pelvic lymph nodes. Eur J Surg Oncol. 2013; 39(10):1150-6. 7. Yanagihara Y, Nishida K, Watanabe R, et al. Feasibility of Laparoscopic Radical Cystectomy in Elderly Patients: A Comparative Analysis of Clinical Outcomes in a Single Institution. Acta Med Okayama. 2019; 73(5):417-418. 8. Hautmann RE, Hautmann SH, Hautmann O. Complications associated with urinary diversion. Nat Rev Urol. 2011; 8(12):667-77. 9. Donat SM, Siegrist T, Cronin A, et al. Radical cystectomy in octogenarians--does morbidity outweigh the potential survival benefits? J Urol. 2010; 183(6):2171-7. 10. Tan WS, Lamb BW, Kelly JD. Complications of Radical Cystectomy and Orthotopic Reconstruction. Adv Urol. 2015; 2015:323157. 11. Shimko MS, Tollefson MK, Umbreit EC, et al. Long-term complications of conduit urinary diversion. J Urol. 2011; 185(2):562-7. 12 Longo N, Imbimbo C, Fusco F, et al. Complications and quality of life in elderly patients with several comorbidities undergoing cutaneous ureterostomy with single stoma or ileal conduit after radical cystectomy. BJU Int. 2016; 118(4):521-6.

CORRESPONDENCE Carlo Giulioni Department of Urology, University Hospital “Ospedali Riuniti”. 71 Conca Street, 60126, Ancona – Italy E-mail: carlo.giulioni9@gmail.com Phone: +39 320/7011978 ORCID: 0000-0001-9934-4011

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