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Article of the week: Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for MIBC

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community, a visual abstract by one of our resident artists and a video produced by the authors. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

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

 

Toshiki Kijima*, Hajime Tanaka*, Fumitaka Koga, Hitoshi Masuda, Soichiro Yoshida*, Minato Yokoyama*, Junichiro Ishioka*, Yoh Matsuoka*, Kazutaka Saito*, Kazunori Kihara* and Yasuhisa Fujii*

 

*Department of Urology, Tokyo Medical and Dental University, Department of Urology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, andDepartment of Urology, National Cancer Center Hospital East, Chiba, Japan

 

Abstract

Objectives

To evaluate the oncological and functional outcomes associated with selective tetramodal bladder‐sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND).

Materials and Methods

In the present study, 154 patients with non‐metastatic muscle‐invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder‐preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC‐recurrence‐free survival (RFS); cancer‐specific survival (CSS); overall survival (OS), and cross‐sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36‐item Short‐Form Health Survey (SF‐36) score.

Results

The median follow‐up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder‐preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5‐year MIBC‐RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post‐void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF‐36, patients had favourable scores, equivalent to the age‐matched references in all the QoL scales.

Conclusion

Selective tetramodal bladder‐preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

Editorial: A new horizon for bladder preservation in muscle‐invasive bladder cancer

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. [1] 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 [2]. 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 [3]. 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. [1] 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 [1]. 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%) [4] and trimodal bladder preservation therapy (11–19%) [5], 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 [67]. 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

References

  1. Kijima TTanaka HKoga F et al. 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 2019124242– 50
  2. 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
  3. Cystoscopic Evaluation Predicting pT0 Urothelial Carcinoma of the Bladder2019. Available at: https://clinicaltrials.gov/ct2/show/NCT02968732. Accessed April 2019
  4. Fahmy NAprikian ATanguay S et al. Practice patterns and recurrence after partial cystectomy for bladder cancer. World J Urol 201028419– 23
  5. Ploussard GDaneshmand SEfstathiou JA et al. Critical analysis of bladder sparing with trimodal therapy in muscle‐invasive bladder cancer: a systematic review. Eur Urol 201466120– 37
  6. Huddart RABirtle AMaynard L et al. Clinical and patient‐reported outcomes of SPARE ‐ a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int2017120639– 50
  7. Huddart RAHall ELewis RBirtle AGroup STMLife and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. BJU Int 2010106:753– 5

 

Video: Selective tetramodal bladder‐preservation therapy for MIBC

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

Abstract

Objectives

To evaluate the oncological and functional outcomes associated with selective tetramodal bladder‐sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND).

Materials and Methods

In the present study, 154 patients with non‐metastatic muscle‐invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder‐preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC‐recurrence‐free survival (RFS); cancer‐specific survival (CSS); overall survival (OS), and cross‐sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36‐item Short‐Form Health Survey (SF‐36) score.

Results

The median follow‐up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder‐preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5‐year MIBC‐RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post‐void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF‐36, patients had favourable scores, equivalent to the age‐matched references in all the QoL scales.

Conclusion

Selective tetramodal bladder‐preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

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