Table 2. Trimodal therapy outcomes based on modern published clinical studies with more than 50 patients.
| Study | Median follow-up (months) | No. of patients | Inclusion criteria | Neoadjuvant or adjuvant chemotherapy | Concomitant chemotherapy | Radiotherapy | CR rate | Salvage RC | Survival |
|---|---|---|---|---|---|---|---|---|---|
| Prospective phase 3 studies | |||||||||
| AlGizawy et al. [2014] (57) | 27 | 80 | T2-3, N0, M0; complete TUR: 60%; hydronephrosis: N/A | None | Cisplatin + gemcitabine (2 cycles) | 46 Gy +20 Gy if initial CR | 83.8% | 32.5% | 3-yr OS: 61%; 3-yr CSS: 69% |
| James et al. [2012] (27) | 69.9 | 182 | T2-T4a, N0, M0; complete TUR: 56.6%; hydronephrosis: N/A | NAC: platinum-based (31.3%) | 5-FU + mitomycin C | 55 Gy or 64 Gy | N/A | 11.4% | 5-yr OS: 48% |
| Tunio et al. [2012] (52) | 60 | 230 | T2-T4, N0, M0; complete TUR: 76.5%; hydronephrosis: 30% | None | Cisplatin weekly x6 | 65 Gy | 80.7% | 21.3% | 5-yr OS: 52%; 5-yr CSS: 47% |
| Shipley et al. [1998] (58) | 61 | 123 | T2-T4a, Nx, M0; complete TUR: 71.5%; hydronephrosis: 19.5% | NAC: MVC (50%) | Cisplatin | 64.8 Gy (n=62); 39.6 Gy +25.2 Gy if CR (n=61) |
58.5% | 20.3% | 5-yr OS: 49% |
| Housset et al.[1993] (59) | 27 | 54 | T2-T4, N0-N1; complete TUR: 46%; hydronephrosis: 42.6% | None | 5-FU + cisplatin | 44 Gy | 79.6% | 27.8%1 | 3-yr OS: 59%; 3-yr CSS: 62% |
| Phase 2 studies | |||||||||
| Coen et al. [2019] (44) | 51.6 | 66 | T2-T4a, Nx, M0; complete TUR: N/A; hydronephrosis: 0% | Adjuvant: GC | 5-FU + cisplatin or gemcitabine | 40 Gy +24 Gy if initial CR | 83.3% | 12.1% | 3-yr OS: 83.3% |
| Mitin et al. [2013] (60) | 60 | 93 | T2-T4a, Nx, M0; complete TUR: N/A; hydronephrosis: 0% | Adjuvant: GC + paclitaxel (60%) | Paclitaxel + cisplatin (49%); 5-FU + cisplatin (51%) |
40.3 Gy + 24 Gy if CR or near CR | 67%; 86%2 | 5.4% | 5-yr OS: 73% |
| Lagrange et al. [2011] (61) | 96 | 51 | T2-T4a, N0, M0; complete TUR: 66%; hydronephrosis: 17% | None | 5-FU + cisplatin | 45 Gy + 18 Gy if initial CR | N/A | 33.3% | 8-yr OS: 36% |
| Choudhury et al. [2011] (40) | 36 | 50 | T2-T3, N0, M0; complete TUR: N/A; hydronephrosis: 10% | None | Gemcitabine weekly | 52.5 Gy | 88% | 10% | 5-yr OS: 65%; 5-yr CSS: 78% |
| Kaufman et al. [2009] (33) | 49.4 | 80 | T2-T4a, N0, M0; complete TUR: N/A; hydronephrosis: 0% | Adjuvant: paclitaxel + gemcitabine (70%) | Paclitaxel + cisplatin | 40.3 Gy + 24 Gy if CR2 | 81%2 | 12.5% | 5-yr OS: 56%; 5-yr CSS: 71% |
| Gogna et al. [2006] (62) | 23 | 113 | T2-T4a, <10 cm tumor; complete TUR: 21.2%; hydronephrosis: N/A | None | Cisplatin weekly | 64 Gy | 70% | 13.3% | 5-yr CSS: 50% |
| Kragelj et al. [2005] (63) | 136 | 84 | T1-T4, M0; complete TUR: 66.7%; hydronephrosis: 14.3% | None | Vinblastine weekly | 63.8-64 Gy | 78% | 4.8%3 | 9-yr OS: 25%; 9-yr CSS: 51% |
| Hussain et al. [2001] (64) | N/A | 56 | T2-T4a, N0/N1; complete TUR: 39.3%; hydronephrosis: N/A; unresectable: 34% | Adjuvant: 5-FU + cisplatin | 5-FU + Cisplatin | 60 Gy | 49% | N/A | 5-yr OS: 32% |
| Fellin et al. [1997] (65) | 46 | 56 | T2-T4, N0/Nx, M0; complete TUR: 18%; hydronephrosis: 41% | NAC: MCV | Cisplatin | 40 Gy + 24 Gy if CR | 50% | 46.4% | 5-yr OS: 55%; 5-yr CSS: 59% |
| Tester et al. [1996] (66) | 52.8 | 91 | T2-T4a, N0-N2/Nx, M0; complete TUR: 0%; hydronephrosis: 20% | NAC: MCV | Cisplatin | 39.6 Gy +25.2 Gy if CR | 74.8% | 40% | 4-yr OS: 62% |
| Large retrospective studies | |||||||||
| Giacalone et al. [2017] (34) | 54.6 | 475 | T2-T4a, N0, M0; complete TUR: 70%; hydronephrosis: 12% | NAC: MCV (25%); adjuvant: varied (45%) | Varied | 41.4 Gy +23.4 Gy if CR | 75% | 29% (at 5-year); 31% (at 10-year) | 10-yr OS: 39%; 10-yr CSS: 59% |
| Krause et al. [2011] (67) | 71.5 | 473 | T2-T4a, Nx, M0; complete TUR: 62%; hydronephrosis: N/A | None | Platinum-based (varied) | Median dose: 53.9 Gy; N=142 RTx alone |
70.4% | 13.3%4 | 10-yr OS: 30%; 15-yr OS: 19% |
| Sabaa et al. [2010] (68) | 71 | 104 | T2-T3a, N0, M0; complete TUR: 100%; hydronephrosis: 0% | Adjuvant: GC (100%) | Cisplatin weekly | 60-65 Gy | 78.8% | 16.3% | 5-yr OS: 59%; 5-yr CSS: 69% |
| Aboziada et al. [2009] (69) | 18 | 50 | T2-T3, N0, M0; complete TUR: 40%; hydronephrosis: 32% | None | Cisplatin weekly | 46 Gy +20 Gy if CR or PR | 72% | 40% | 1.5-yr OS: 100%; 1.5-yr CSS: 84% |
| Perdonà et al. [2008] (70) | 66 | 121 | T2-T4, Nx, M0; complete TUR: 81%; hydronephrosis: 8.3% | NAC: MCV | Cisplatin or carboplatin | 65 Gy | 85.7% | 20.2% | 5-yr OS: 72%; 5-yr CSS: 79% |
| Weiss et al. [2007] (71) | 27 | 112 | T1-T4, N2, M0; complete TUR: 84.8%; hydronephrosis: 20% | None | 5-FU + cisplatin | 55.8–59.4 Gy | 88.4% | 17.0% | 5-yr OS: 74%; 5-yr CSS: 82% |
| Rödel et al. [2002] (37) | 36 | 415 | T1-T4; complete TUR: 61.0%; hydronephrosis: N/A | None | Cisplatin +/− 5-FU or carboplatin, N=289 | 54 Gy; N=126 RTx only | 72% | 20% | 10-yr OS: 31%; 10-yr CSS: 42% |
1, excluding 18 patients (33.3%) who were treated with primary RC after CR to induction treatment; 2, CR defined as pT0, Ta, Tis on post induction tumor site biopsy; 3, only 14.3% of patients with persistent or recurrent invasive tumors underwent salvage RC; the other patients refused surgery for tumor dissemination, locally advanced inoperable tumor or poor performance status; 4, rate of RC in non-responders. TUR, trans-urethral resection; CR, complete response; RC, radical cystectomy; OS, overall survival; CSS, cancer-specific survival; 5-FU, 5-fluorouracil; N/A, not available; NAC, neoadjuvant chemotherapy; MCV, methotrexate; cisplatin; vinblastine; PR, partial response; GC, gemcitabine + cisplatin; RTx, radiotherapy.