We are witnessing a shift toward treatment de‐escalation in muscle‐invasive bladder cancer. Patients diagnosed with muscle‐invasive bladder cancer have traditionally faced two treatment options: (1) radical cystectomy with urinary diversion or (2) chemoradiation, both of which can impact quality of life and subsequent morbidity while variably influencing recurrence rates. Recent research has turned toward treatment de‐escalation in an attempt to preserve the bladder while maintaining survival rates. In this issue of BJUI, Kijima et al.  propose a tetramodal treatment regimen which combines chemoradiation with partial cystectomy, in an attempt to avoid radical cystectomy without compromising recurrence and survival. Similar ongoing clinical trials are beginning to explore the role of treatment de‐escalation by potentially avoiding cystectomy and/or radiation altogether. Dr Daniel Geynisman is leading a phase II trial at Fox Chase Medical Centre to investigate the role of single‐modality chemotherapy . In that study, therapy is individualized by applying a risk‐adapted approach to identify genetic mutations in cancer cells to predict whether chemotherapy will be effective in eliminating all cancer and preventing future recurrence and metastasis. A related study led by Dr Alexander Kutikov is assessing the reliability of cystoscopic evaluation in predicting pT0 urothelial carcinoma of the bladder at the time of radical cystectomy . By identifying urine biomarkers, investigators could potentially identify those patients who will respond completely to neoadjuvant chemotherapy, thus obviating the need for subsequent cystectomy.
While these studies have not yet provided definitive evidence to forgo definitive therapy (whether it be chemoradiotherapy or radical cystectomy), in this issue of BJUI, Kijima et al.  propose similar de‐escalation efforts to promote bladder preservation in a carefully selected population, by preserving quality of life with chemoradiation while addressing the potential increased risk of recurrence with partial cystectomy. The authors report the oncological and functional outcomes of a series of patients who underwent a new tetramodal bladder preservation treatment combination for muscle‐invasive bladder cancer . After patients underwent maximal transurethral bladder tumour resection, induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection, only 4% of patients experienced recurrence of muscle‐invasive bladder cancer over a median follow‐up of 2 years, with an overall cancer recurrence rate of 18% and a 5‐year cancer‐specific survival of 93%.
When comparing these findings with the bladder cancer recurrence rates after partial cystectomy in the setting of muscle‐invasive disease (~40%)  and trimodal bladder preservation therapy (11–19%) , the findings presented in this paper are remarkable. Although the lower recurrence rate observed in this patient series may be influenced by a shorter follow‐up time than other studies looking at similar outcomes in patients treated for muscle‐invasive bladder cancer, the results of this paper demonstrate a promising frontier in bladder cancer treatment, combining the benefits of trimodal therapy with the extirpative intent of surgery while preserving the bladder. The long‐term (>5 year) cancer‐specific outcomes of these patients, however, remain unknown and are important to examine in order to contribute to our understanding of the true efficacy of this bladder cancer management strategy.
Given that treatment de‐escalation and bladder preservation share the goal of reduced morbidity and improved quality of life, functional outcomes after tetramodal therapy remain unclear yet critical. Differences in functional outcomes between cystectomy and bladder preservation also remain unclear, as randomized trials in this space are challenging to accrue, a lesson learned with the SPARE trial [6, 7]. Certainly, radiation and partial cystectomy are interventions that can decrease bladder capacity and result in irritative LUTS. The extent to which tetramodal therapy impacts these functional outcomes will be important to address moving forward. Despite the absence of a pre‐treatment baseline symptom profile, the overall favourable urinary quality‐of‐life score and reasonable bladder capacity after treatment completion are encouraging and suggest adequate patient tolerability.
As we usher in a new era of personalized medicine in muscle‐invasive bladder cancer, tetramodal bladder preservation treatment may have a role in bladder preservation by decreasing recurrence while maintaining quality of life. We look forward to long‐term data regarding oncological and functional outcomes to determine if this treatment strategy offers a significant benefit when compared with the ‘gold standard’ therapies for muscle‐invasive bladder cancer.
by Pauline Filippou and Angela B Smith
- Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle‐invasive bladder cancer: oncological and functional outcomes of 107 patients. BJU Int 2019; 124: 242– 50 , , et al.
- Phase II Trial of Risk Enabled Therapy after Initiating Neoajduvant Chemotherapy for Bladder Cancer (RETAIN BLADDER), 2018. Available at: https://www.carislifesciences.com/wp-content/uploads/2018/02/ASCO-GU-A-Phase-II-Trial-of-Risk-Enabled-Therapy-After-Initiating-Neoadjuvant-Chemotherapy-for-Bladder-Cancer-RETAIN-BLADDER.pdf. Accessed April 2019
- Cystoscopic Evaluation Predicting pT0 Urothelial Carcinoma of the Bladder, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT02968732. Accessed April 2019
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- Clinical and patient‐reported outcomes of SPARE ‐ a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int2017; 120: 639– 50 , , et al.
- Group STM. Life and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. BJU Int 2010; 106:753– 5 , , , ,