Introduction
Node-positive bladder cancer (NPBC) is associated with poor outcomes compared to node-negative bladder cancer (NNBC) with 5-year recurrence-free rates of 35% vs. 78%1. In a subset of NPBC patients, neoadjuvant chemotherapy (NAC) and surgery can provide long-term control (5-year cancer-specific survival 63.5%2) but little has been reported on pelvic radiotherapy in bladder cancer. The IMPART study assessed the feasibility of delivering radical intensity-modulated radiotherapy (IMRT) to the bladder and pelvic nodes.
Methods
38 patients with NPBC or high-risk NNBC (e.g. cT3b/T4, small cell histopathology) were recruited between June 2009 and November 2012.
IMRT was delivered to the whole bladder, tumour bed, pelvic nodes and involved nodes with doses of 52Gy, 64Gy, 52Gy and 60Gy respectively in 32 fractions. NAC and/or concurrent chemotherapy were permitted. Data was analysed using STATA 13.1 for Windows and Excel.
Results
Median age was 71 years (range 47-88 years). 31/38 (82%) were male. 3/38 (8%) had a previous cystectomy. 22/38 (58%) had NPBC (N1= 9 (24%), N2= 9 (24%), N3= 4 (11%)).
31/38 patients (82%) received NAC and 18/38 (47%) concurrent chemotherapy. 37/38 (97%) had radiotherapy planned as per protocol and 35/38 (92%) completed radiotherapy as planned. Grade 3 gastrointestinal and genitourinary acute toxicity rates were 20% and 6% respectively. At 1 year, the G3 late toxicity rate was 5%.
27/38 (71%) patients had disease recurrence. Sites of relapse, in order of frequency, were distant metastatic (12/38, 32%), local muscle-invasive bladder disease (7/38, 18%) and local non-muscle-invasive only (6/38, 16%). Only 2/38 (5%) had pelvic node relapse. 1-, 2- and 5-year pelvic relapse-free survival were 55%, 37% and 26% respectively.
2/38 patients (5%) died before/during treatment from unrelated causes and 4/38 (11%) died with no recorded relapse. At a median follow-up of 5.2 years, 5/38 patients (13%) remain alive and recurrence-free. Median overall survival was 1.9 years (95% CI 1.1-3.8) with 1-, 2- and 5-year overall survival of 68%, 50% and 34% respectively.
Conclusion
Delivering IMRT to the bladder and pelvic nodes in NPBC or high-risk NNBC is feasible with low toxicity and pelvic nodal recurrence rates. Relapse patterns suggest that strategies targeting local bladder recurrence (e.g. radiation dose escalation, concomitant therapies), and reducing distant metastasis (e.g. immunotherapy) are required to improve patient outcomes.
References
- Stein, J.P., et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19, 666-675 (2001)
- Meijer, R.P., et al. Induction chemotherapy followed by surgery in node positive bladder cancer. Urology 83, 134-139 (2014).