Bladder Cancer

March Madness: The BC2001 & BCON Bladder Preservation Bonanza

The March 20-21st Global Radiation Oncology Twitter Journal Club (#RadOnc #JC) will be on bladder cancer! #JC will begin Saturday, March 20th at 8am CST and go through Sunday, March 21st, culminating in the Live Hour from 1-2pm CST Sunday, March 21st.

When bladder preservation therapy emerged as a management option for muscle invasive bladder cancer (MIBC) over 40 years ago, the initial question clinicians faced was whether oncologic outcomes from bladder preservation could rival those seen with radical cystectomy. While there is no prospective, randomized data directly comparing these approaches following early closure of the UK MRC Selective bladder Preservation Against Radical Excision (SPARE) trial,1 high quality retrospective data including those from a large meta-analysis suggested no differences in overall survival, disease-specific survival, or progression-free survival between the two management strategies.2,3

Since then, new questions emerged:

  • Selection Criteria: Which patients are best suited for bladder preservation?

While the RTOG approach often utilized in the USA advocates for strict criteria including maximal transurethral resection of bladder tumor (TURBT), ongoing investigations in the UK explore the omission of TURBT entirely with the BladderPath study randomizing patients to TURBT or MRI for clinical staging.4

  • Systemic Therapies: Which radiosensitizing systemic should be used (if any)?

The BC2001 trial randomized patients to radiotherapy alone versus concurrent chemoradiotherapy with 5-FU and mitomycin-C and found an improvement in locoregional control and a trend towards improved bladder cancer-specific survival with the addition of chemotherapy.5 The BCON trial investigated the effect of hypoxia modification with the addition of carbogen and nicotinamide (CON) and found improvements in 5-year overall survival and recurrence-free survival.6

  • Technique: What is the optimal field design? Target the full or partial bladder? Treat nodes or not? Conventional or hypofractionation? Boost or no boost?

Based on the great variety of options available for radiotherapeutic management, there is a great deal of heterogeneity within bladder preservation therapy itself across the globe. As the BC2001 trial incorporated a partial 2-by-2 factorial design randomizing to treatment of the whole bladder versus a partial bladder volume while allowing for both conventionally fractionated (64 Gy in 32 fractions) and hypofractionated (55 Gy in 20 fractions) schedules, up until very recently, the only data guiding us on these matters was based on a subgroup analysis indicating no differences based on field design or fractionation.5

     …that is, until very recently.

For the March 2021 #RadOnc #JC we’ll be discussing one of the biggest bladder cancer plays[IP1]  of 2021:

     Choudhury, A., et al. (2021). “Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials.” The Lancet Oncology 22(2): 246-255. [link]

This article is open access and we hope this encourages more inclusive participation. We’ll be joined by lead discussants including the paper’s authors from the UK: Professors Ananya Choudhury (@achoud72), Emma Hall (@EmmaHall71), YeePei Song (@syeepei), and Nuria Porta (@NPortaStat); plus genitourinary (GU) radiation oncology specialists Drs. Sophia Kamran (@sophia_kamran) from the USA, Vendang Murthy (@VedangMurthy) from India, and Paul Sargos (@PaulSargos) from France.


Choudhury et al reported on 782 patients with a 10-year median follow-up and described a lower risk of invasive local recurrence for patients receiving 55 Gy in 20 fractions when compared to those receiving conventional fractionation with 64 Gy in 32 fractions, with some caveats…

Guiding Topics:

T1. Background: What is the rationale for bladder preservation? What is your current practice? What criteria do you utilize when determining if a patient is a good candidate for bladder preservation?

T2. Methods: What is an individual patient data meta-analysis and how does it differ from other reviews? What is a 2 x 2 factorial design? What statistical models were used and why?

T3. Results: What were the main outcomes for radiation fractionation and use of systemics? What imbalances were found in the meta-analysis and how was this managed?  

T4. Discussion: What rationales may explain the findings of improved local control with hypofractionation? Impact of differences in radiation field design? Which patients should be treated with hypofractionation to the bladder only, nodal irradiation, or conventional fractionation?  Role of immunotherapy, boost, or hypoxia modifying agents indicated?  In which bladder cancer populations does this study not apply.

T5. Next Steps: Where is more research most needed (i.e. omitting maximal TURBT, extensive in situ disease, or hydronephrosis)? 


T6. #PatientsIncluded & More:  What matters most for patients & our allied/interdisciplinary colleagues facing bladder cancer?  How can #RadOnc #JC and this study help?

Some tips to participate:

  • Guidelines on how to sign up & participate
  • Disclaimer for ways to keep #RadOnc #JC rewarding and professional. If you’re not ready, just lurk & tune in to the conversation.

References:


Open & Patient-Focused:
1. Choudhury, A., et al. (2021). “Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials.” The Lancet Oncology 22(2): 246-255. [link] https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30607-0/fulltext

2. M Fowler. Lower-Dose Hypofractionated Radiotherapy Schedule Proves Effective for Patients With Locally Advanced Bladder Cancer. Feb 25, 2021. https://www.cancernetwork.com/view/lower-dose-hypofractionated-radiotherapy-schedule-proves-effective-for-patients-with-locally-advanced-bladder-cancer

3. Bladder Preservation with Combined-Modality Therapy (CMT). Bladder Cancer Advisory Network. Accessed Mar 11 2021.https://bcan.org/bladder-preservation/

Other

1. Huddart RA, Birtle A, Maynard L, et al. Clinical and patient-reported outcomes of SPARE – a randomised feasibility study of  selective bladder preservation versus radical cystectomy. BJU Int. 2017;120(5):639-650. doi:10.1111/bju.13900

2. Kulkarni GS, Hermanns T, Wei Y, et al. Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal  Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic. J Clin Oncol  Off J Am Soc Clin  Oncol. 2017;35(20):2299-2305. doi:10.1200/JCO.2016.69.2327

3. Vashistha V, Wang H, Mazzone A, et al. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive  Bladder Cancer: A Systematic Review and Meta-Analysis. Int J Radiat Oncol Biol Phys. 2017;97(5):1002-1020. doi:10.1016/j.ijrobp.2016.11.056

4. James ND, Pirrie S, Liu W, et al. Replacing TURBT with mpMRI for staging MIBC: Pilot data from the BladderPath study. J Clin Oncol. 2020;38(6_suppl):446. doi:10.1200/JCO.2020.38.6_suppl.446

5. Hall E, Hussain SA, Porta N, et al. BC2001 long-term outcomes: A phase III randomized trial of chemoradiotherapy versus radiotherapy (RT) alone and standard RT versus reduced high-dose volume RT in muscle-invasive bladder cancer. J Clin Oncol. 2017; 35:6_suppl, 280-280

6. Hoskin PJ, Rojas AM, Bentzen SM, Saunders MI. Radiotherapy with concurrent carbogen and nicotinamide in bladder carcinoma. J Clin Oncol. 2010 Nov 20;28(33):4912-8. doi: 10.1200/JCO.2010.28.4950.


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