Radiation Oncology/Bladder/Randomized

Bladder Cancer Level I Evidence

In the process of being cross-linked ...

Superficial Bladder Cancer

 * MRC T1 Bladder (1991-2003)
 * Randomized, 2 strata. 210 patients with pT1G3 TCC after TURBT
 * Unifocal disease & no Tis: Arm 1) observation vs. Arm 2) RT 60/30
 * Multifocal disease and/or Tis: Arm 1) intravesical therapy (MMC or BCG) vs. Arm 2) RT 60/30
 * 2007 PMID 17631326 -- "A randomized trial of radical radiotherapy for the management of pT1G3 NXM0 transitional cell carcinoma of the bladder." (Harland SJ, J Urol. 2007 Sep;178(3 Pt 1):807-13; discussion 813. Epub 2007 Jul 16.)
 * Outcome: No difference in PFS, OS, or cystectomy rate
 * Conclusion: No evidence that adjuvant RT after TURBT is better than more conservative treatment; prognosis poor regardless

Definitive RT vs Preop RT + Cystectomy

 * Danish National Bladder Cancer Group, DAVECA 8201 (1983-1986) -- Definitive RT vs Preop RT + cystectomy
 * Randomized. 183 patients. cT2-T4a. Arm 1) Pre-op RT 40 Gy + cystectomy vs Arm 2) Radical RT 60 Gy with cystectomy for salvage.
 * 1991 PMID 1785004 &mdash; "Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group." (Sell A, Scand J Urol Nephrol Suppl. 1991;138:193-201.) Median F/U 4.2 years
 * Outcome: Salvage cystectomy 28%. Local/pelvic failure Cystectomy 7% vs RT 35%, no difference in DM. No difference in OS (29% vs 23%)
 * No difference in OS (29% vs 23%). Local/pelvic recurrence lower (6.8% surgery vs 35% RT). No difference in DM.
 * Conclusion: Improved pelvic control with surgery, but no difference in survival


 * MD Anderson (1964-1970) -- Definitive RT vs Preop RT + cystectomy
 * Randomized. 67 patients, Stage B2-C. Arm 1) definitive RT 60 Gy vs Arm 2) Preoperative RT 50 Gy followed by cystectomy
 * 1977 PMID 402205 -- "Bladder cancer: superiority of preoperative irradiation and cystectomy in clinical stages B2 and C." (Miller LS, Cancer. 1977 Feb;39(2 Suppl):973-80.)
 * Outcome: 5-year OS RT 16% vs preop RT + cystectomy 46% (SS)
 * Conclusion: Institutional policy has changed to preoperative RT with planned cystectomy, except for patients declining or medically unfit for surgery

RT Alone vs Chemo-RT

 * NCI Canada (1985-1989) -- RT vs RT + concurrent cisplatin
 * Randomized. 99 patients. cT2-T4b, either definitive therapy or pre-cystectomy (selected a priori). Arm 1) RT 40/20 or 60/30 vs Arm 2) Same RT with concurrent cisplatin 100 mg/m2 Q2W x3 cycles
 * 1996 PMID 8918486 &mdash; "Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group." (Coppin CM, J Clin Oncol. 1996 Nov;14(11):2901-7.) Median F/U 6.5 years
 * Outcome: 5-year pelvic failure RT 59% vs chemo-RT 40% (SS), first site pelvic failure 52% vs chemo-RT 29% (SS), held in both definitive and preop groups. No difference in DM. 3-year OS 47% vs 33% (NS). If definitive treatment, bladder preservation RT 36% vs chemo-RT 70% (NS)
 * Conclusion: Concurrent cisplatin may improve pelvic control and bladder preservation, but not overall survival.

Induction MCV chemotherapy

 * RTOG 89-03 (1990-93) -- Selective chemo-RT bladder sparing +/- induction MCV x2 cycles
 * Phase III. Stopped prematurely due to severe neutropenia and sepsis. 123 of 174 patients. cT2-T4a. Randomized to Arm 1) 2 cycles of MCV before, or Arm 2) no MCV before RT 39.6/22 with concurrent cisplatin 100 mg/m2 q3w x2 courses (per RTOG 88-02), cystoscopy 4 weeks later. If CR, consolidative RT 25.2/14 with concurrent cisplatin 100 mg/m2, else radical cystectomy. Total RT dose 64.8/36
 * 1998 PMID 9817278 &mdash; "Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03." (Shipley WU, J Clin Oncol. 1998 Nov;16(11):3576-83.) Median F/U 5 years
 * Outcome: pCR MCV+ 61% vs MCV- 55%. 5-year bladder preservation 36% vs 40% (NS). DM 33% vs 39% (NS). 5-year OS 48% vs 49% (NS) Predictors for worse outcome hydronephrosis and incomplete TURBT
 * Conclusion: 2 cycles of MCV did not increase CR rate, change DM rate, or impact OS. High toxicity.

Partial bladder irradiation

 * Christie Hospital, UK (1993-99) -- whole bladder 52.5/20 vs partial bladder 57.5/20 or 55/16
 * Randomized. 149 patients. T2-T3N0M0, unifocal TCC <= 7cm. Randomized to whole bladder conformal RT (52.5/20, 2.63 Gy/fx) or partial bladder RT (CTV + 1.5 cm) in 4 wks (57.5/20, 2.88 Gy/fx) or 3 wks (55 Gy/16, 3.44 Gy/fx). No chemo
 * 2004 PMID 15093917 &mdash; "Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy." (Cowan RA, Int J Radiat Oncol Biol Phys. 2004 May 1;59(1):197-207.) Median F/U 5.8 years for living patients
 * Outcome: 5-year local control WBRT 58% vs PBRT4 59% vs PBRT3 34% (NS), overall 50%. 87% of recurrences within irradiated tumor volume. DM 17% vs 25% vs 22% (NS). 5-year OS 58% (NS)
 * Toxicity: Well tolerated. 85% of patients alive at 5 years preserved their bladder
 * Conclusion: Comparable outcome between whole bladder RT and partial bladder RT

Accelerated irradiation

 * Cooperative Urological Oncology Group, UK (1988-1998) -- AHFX 60.8/32 BID vs CF 64/32 QD
 * Randomized. 229 patients with T2-T3 N0-N1 bladder cancer. Arm 1) AF split-course 60.8/32 BID (22.8/12 + 19/10 + 19/10) vs. Arm 2) Conventional CF 64/32. Primary endpoint local control
 * 2005 PMID 15878099 -- "A randomised trial of accelerated radiotherapy for localised invasive bladder cancer." (Horwich A, Radiother Oncol. 2005 Apr;75(1):34-43. Epub 2004 Nov 25.)
 * Outcome: LR AF 32% vs. CF 29% (NS); 3-year OS 47% vs. 54% (NS); 5-year OS 40% vs. 37% (NS)
 * Toxicity: Acute AF 44% vs. CF 26% (SS); Late toxicity (if FFR 2 years): Grade 2+ AHFX 44% vs. conventional 38% (NS). 2 treatment-related deaths on AHFX arm
 * Conclusion: No benefit for AHFX over conventional fractionation, worse acute GI toxicity