Dose-escalated RT for MIBC (retrospective)
ForMIBC T2-3, M0 (node+ allowed), post-TURBT curative RT ± concurrent chemo
TL;DR2y invasive local recurrence 5.5% vs 27.5% with SIB dose escalation in MIBC TMT (adjusted SHR 0.20, p=0.035); no OS, MFS or G2+ toxicity difference.
Pattern of failure is the RT read: standard-dose invasive failures sat at the original tumour site (14 within vs 2 outside), and the escalated cohort had 1 invasive failure inside the boost. A 60Gy/20fx or 70Gy/32fx SIB to the primary on daily CBCT carried no G2+ GU/GI cost, which supports testing primary-tumour escalation in TMT.
In a unifocal MIBC TMT candidate without hydronephrosis, this supports a primary-tumour SIB as a trial-worthy option rather than routine practice; it does not extend to multifocal disease, which the escalated cohort never included.
Standard-dose invasive failures clustered at the original tumour site (14 within vs 2 outside), the dose-limited failure pattern a primary boost targets. The SIB (up to 60Gy/20fx or 70Gy/32fx) on daily CBCT added no G2+ GU/GI toxicity at 23 mo median f/u, so the open question is late effects rather than deliverability.
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Multicentre retrospective cohort from 3 centres, March 2015 to May 2025. N=107: 39 dose-escalated vs 68 standard. Median follow-up 23 mo (range 3-104).
Curative-intent MIBC after TURBT, RT with or without concurrent chemo; node-positive allowed if M0. Metastatic or palliative-intent pts excluded. 51% received no chemo, mostly for poor PS or comorbidity.
Standard: 55Gy/20fx or 64Gy/32fx whole bladder. Escalation: SIB up to 60Gy/20fx or 70Gy/32fx to the primary lesion. Empty-bladder CT sim, daily CBCT, MRI/FDG PET fusion in select pts.
2-year local control for invasive and non-invasive disease, metastasis-free survival, OS, bladder preservation and toxicity. Invasive recurrence analysed by Fine-Gray competing-risk models.
Invasive recurrence was the only endpoint that separated (adjusted SHR 0.20, p=0.035); non-invasive recurrence, metastasis and OS did not differ. Full arm values in the table.
| Endpoint | Escalated (n=39) | Standard (n=68) | Effect |
|---|---|---|---|
| 2y invasive local recurrence | 5.5% | 27.5% | SHR 0.20 (0.05-0.89), p=0.035 (MVA, T stage) |
| 2y non-invasive recurrence | 6.7% | 9.9% | SHR 0.88 (0.23-3.33); MVA p=0.79 |
| 2y metastasis | 21.1% | 32.3% | MVA p=0.75 |
| 2y OS | 71.1% | 64.4% | p=0.5 |
| G2+ GU toxicity | 17.9% | 22.1% | p=0.8 |
| G2+ GI toxicity | 5.1% | 7.4% | p=0.9 |
| Cohort / site | Invasive | Non-invasive |
|---|---|---|
| Escalated, within boost field | 1 | 0 |
| Escalated, outside boost field | 1 | 3 |
| Standard, within original tumour site | 14 | 2 |
| Standard, outside original tumour site | 2 | 5 |
G2+ GU 17.9% vs 22.1% and G2+ GI 5.1% vs 7.4% (escalated vs standard), no difference (p=0.8, p=0.9). G3 toxicity only in 2 standard-dose pts; no early cessation.
BC2001 and BCON built modern TMT on radiosensitisation of whole-bladder RT, not on dose to the primary. RAIDER tested tumour-focused adaptive escalation prospectively; this series adds a routine-practice, CBCT-era hypofractionated experience in the same direction.
Asymmetric outcome ascertainment: 3 standard-arm recurrences were imaging-only and presumed invasive, while every escalated recurrence was cystoscopy-confirmed. Chemo use (56% vs 44%) and hypofractionation (97% vs 87%) also favoured the escalated cohort, and f/u starts at 3 mo, short for late bladder toxicity.
The in-field failure pattern in the standard cohort gives escalation a mechanistic rationale; the magnitude is not trustworthy given selection. Bladder preservation was high in both groups partly because relapsed pts were unfit for cystectomy, so it conflates control with fitness.
Retrospective, non-randomised; escalated cohort selected (all unifocal, less hydronephrosis). Few invasive events (2 vs 16), adjusted for T stage only, so dose cannot be separated from selection.
- Does SIB primary-tumour escalation reduce invasive recurrence in a randomised TMT trial?
- Is the benefit preserved in multifocal MIBC?
- Late GU toxicity beyond 2 years with a 60Gy/20fx or 70Gy/32fx boost? recruiting Hypofractionated IMRT With Concurrent Chemotherapy in Muscle-invasive Bladder Cancer (HIRACUM) Phase NAn=53 · primary completion 2026-12 · MIBC chemo-hypo-IMRT 56-64Gy/20fx, toxicity + QoL
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The longer read
The case for dose escalation in bladder preservation rests on a pattern-of-failure argument, and this series supplies that argument more convincingly than its headline hazard ratio. In the standard-dose cohort, invasive failures sat overwhelmingly at the original tumour site (14 within versus 2 outside), which is what you would expect if dose to the gross tumour, not field extent, is the limiting factor. Boosting the primary through a simultaneous integrated boost while holding the whole-bladder prescription at 55Gy/20fx or 64Gy/32fx is the logical response, and the escalated cohort recorded only 2 invasive recurrences, one of them inside the boost field. The direction is biologically coherent. The open question is how much of the magnitude survives the design.
Less than the SHR of 0.20 implies. Every escalated patient had unifocal disease, against 65% of the standard cohort, and hydronephrosis, a marker of deeper or bulkier tumour and an independent adverse factor for OS in this same dataset, was present in 10% versus 28%. Unifocal tumours without hydronephrosis are exactly where a boost is technically easy to plan and where local control would be better regardless of dose. A Fine-Gray model adjusting only for T stage, with 2 invasive events on one side, cannot separate dose from that selection, and an interval running from 0.05 to 0.89 shows how fragile the point estimate is. Ascertainment tilts the same way: three standard-arm recurrences were imaging-detected in pts unfit for cystoscopy and classified as presumed invasive, while every escalated recurrence was cystoscopy-confirmed. Frailer pts, worse tumours and softer outcome definitions all sat in the comparator arm.
Against the trials that define TMT practice, the relevance is specific rather than general. BC2001 and BCON built the modern approach on radiosensitisation of whole-bladder RT, and neither asked whether more dose to the primary helps. RAIDER approached that question prospectively with adaptive tumour-focused planning. This series belongs next to that work as routine-practice evidence that a primary boost is deliverable in hypofractionated schedules under daily CBCT, without an early toxicity price. That is a feasibility and hypothesis contribution, not an efficacy one.
Toxicity is the more reassuring part. G2+ GU and GI rates were not higher with escalation, and grade 3 events occurred only in the standard cohort. But a median follow-up of 23 months, with a range starting at 3, is short for contracture, haematuria and reduced capacity, which is where a boost would be expected to cost. Absence of an early signal is not absence of late harm.
The null metastasis and OS results should not be read as evidence against escalation. In a cohort where half did not receive chemotherapy because of poor PS, and where chemo omission and hydronephrosis dominated survival, a local-control gain in 107 pts would not be expected to reach OS. Bladder preservation was high in both groups partly because relapsed pts were too unfit for cystectomy, so that endpoint conflates control with fitness. What would make this result wrong is simple: if unifocal, non-hydronephrotic tumours do this well at standard dose. Only a randomised or carefully matched prospective comparison answers that, and this dataset is a reasonable justification for running one.