Table 3.
Time to recurrence rate/freedom from recurrence and recurrence-free or disease-free survival in adjuvant trials in rectal cancer with a surgery alone group and where systemic chemotherapy was provided in the experimental group.
| Trial/Reference | Inclusion Dates | Number Control Pts/Total Number Pts | Number of Patients in Stage I/II/III | Proportion Receiving ACT | Preoperative Treatment |
Follow-Up Time (Years) |
TTR/FFR | RFS/DFS | Comments |
|---|---|---|---|---|---|---|---|---|---|
| GITSG [92] | 1975–1980 | 62/227 | 0/21/37 | 0 | None | 5 | II: 67% III: 32% |
Before TME | |
| NSABP R01 [93] | 1977–1986 | 179/555 | 0/67/109 | 0 | None | 5 | 29% | Before TME, DM risks given in [94] | |
| Gunderson et al., 5 US trials pooled [94] | 1977–1986 | 179/3791 | 0/67/109 | 0 | None | 5 | II: ~60% III: ~40% |
Present DM rates of the NSABP-trial, 40% pT1–2 N+, 60% pT3 N1, 34% pT3 N0, 59% pT3 N2 | |
| QUASAR uncertain [46] | 1994–2003 | 474/948 | 0/407/67 | 0 | 6% neo-RT (8% adj-RT) |
5 | 68% | Before TME, projected 5 year | |
| EORTC 22921 [95] | 1993–2003 | 505/1011 | NR | 0 | RT or CRT | 5 | 65% | 52% | 90% T3, 10% T4. 34% DM overall |
| Gerard et al., FFCD [96] | 1993–2003 | 0/742 | 87% T3, 13% T4 | 70% | RT or CRT | 5 | 57% | Before TME, LR 17% RT vs 8% CRT, adjuvant chemo planned both groups | |
| PROCTOR/SCRIPT [59] | 2000–2013 | 221/437 | 0/32/189 | 0 | 5 × 5 or CRT | 5 | 60% | Systemic recurrence 39%, local 8% | |
| Chronicle [60] | 2004–2008 | 59/113 | 31/28 | 0 | CRT | 3 | 73% | ||
| Stockholm III [97] | 1998–2013 | 920 | NR | About 15% | 5 × 5 direct or delayed surgery, RT 2 × 25 | 5 | projected 79% | 65% | Intermediate risk tumors. ACT only recorded in patients included from 2007. ypTN I/II/III/IV/X = 271/250/278/25/11 |
| Bujko et al., Polish I trial [98,99] | 1999–2002 | 316 | 170/113 | NR | 5 × 5 direct surgery or CRT | 4 | 67% | 57% | Locally advanced, low-lying |
| Polish II trial [100] | 2008–2014 | 254/515 | NR | 39% | CRT | 8 | 67% | 41% | TNT= FF-DM |
| RAPIDO [101] | 2011–2016 | 452/920 | 42% | CRT | 3 | 73% | 70% | Locally advanced, ugly tumours, TNT provided in experimental group, RFS/DFS = DrTF, TTR/FFR = FF-DM | |
| PRODIGE 23 [102] | 2012–2017 | 230/461 | 69% | CRT | 3 | 72% | 69% | TNT in experimental group, RFS/DFS = FF-DM | |
| Valentini et al., Five European trials pooled [103] | 1993–2003 | 1209/2795 | 1879/833 | 56% | RT/CRT | 5 | Distant all 69%, ypN0 79%, ypN1–2 48%, local all 87% | Created a nomogram. ACT limited effect. Few events after 5 to 10 years (distant all from 69% to 66%) | |
| Bregoum et al. [7] | 1992–2013 | 598/1196 | 207/391 | 0 | 5 × 5 or CRT | 5 | 63% | Meta-analysis 4 trials, TME, FF-DM |
The old trials were identified in one meta-analysis/systematic overview [77] and the more recent ones in three overviews/meta-analysis [7,8,103] and four further studies where the recurrence risk could be described after preoperative RT [97] or CRT [98,99,100,101] were identified. The key publications for all trials were scrutinized to find information of recurrence rates and not only DFS or OS as mostly presented in the overviews. Abbreviations: DFS = disease-free survival, OS = overall survival, RFS = recurrence-free survival, EFS = event-free survival, TTR = time to recurrence, FFR = freedom from recurrence (100-recurrence rate in % as provided in the articles), TME = total mesorectal excision, DM = distant metastasis, RT = radiotherapy, CRT = chemoradiotherapy to 46–50 Gy, 5 × 5 = 5 times 5 Gy radiotherapy in one week, FF-DM = freedom from distant metastasis, DrTF = disease-related treatment failure, ACT = adjuvant chemotherapy, TNT total neoadjuvant treatment evaluated in the experimental arm.