Although with shorter follow-up, several prospective studies have been published in recent years. The American ACOSOG Z6041 multicenter phase 2 trial recruited 79 patients who underwent LE after neoadjuvant chemoradiotherapy.
11 At a median follow-up of 56 months, the estimated 5-year OS and DFS were 90.9% and 79.3%, respectively. As in our series, two out of five local recurrences were found in patients with a pCR. This is not surprising as the LE neither includes all the area of the pre-treatment primary tumor, nor removes the mesorectal nodes. Moreover, an incomplete histopathological examination cannot be excluded. In their prospective trial, Lezoche et al. randomized 100 patients who, after neoadjuvant chemoradiotherapy, underwent LE (
n = 50) or standard laparoscopic TME (
n = 50).
19 At a median follow-up of 9.6 years, the cancer-related survival rate was 89% and the OS was 72%, without any differences compared with the laparoscopic TME arm. The rate of local recurrence was 8%. Although both previous trials included patients with favorable cases (small rectal cancer, clinically staged as cT2N0), the outcomes are comparable with our study. More recently, prospective studies included clinical T2-T3 rectal cancer.
14,
15 At a median follow-up of 60 months, Rullier et al. reported no difference between LE and TME arms, either in terms of 5-year local recurrence (7% vs. 7%), or in terms of metastatic disease (18% vs. 19%), OS (84% vs. 82%), or DFS (70% vs. 72%).
14 Furthermore, at a median follow-up of 53 months, Stijns et al. reported a 5-year actuarial local recurrence rate of 7.7%, DFS of 81.6%, and OS of 82.8%, respectively.
15 It should be noted that in our study, 60% of patients were staged as cT3 at baseline, whereas in the trials of Rullier et al. and Stijns et al. the rates of cT3 were 45% and 29%, respectively.
13,
14 These findings may suggest that the rectum preservation strategy should be based on clinical response to neoadjuvant therapy instead of clinical baseline staging. A clear message derived from our and the previous trials is that the risk of local recurrence after LE is higher than after TME surgery. In order to reduce this risk, patients with unfavorable histologic features, particularly ypT2-3 tumors, should undergo an early completion radical surgery. In three of five patients with local recurrences, the completion radical surgery was refused. Patients should be informed that LE is basically an excisional biopsy and that there is an increased risk of local recurrence, particularly for those patients refusing the recommended completion radical surgery (Table
3). Moreover, as all local recurrences were observed between 31 and 49 months after LE, a close and prolonged follow-up should be strongly recommended. This close follow-up is also required in patients with a pCR, as local recurrences have been observed in these patients.
Although this study reports on the LE approach, some considerations related to the watch-and-wait approach seem appropriate. Compared with the watch-and-wait policy, the LE approach is associated with postoperative morbidity and the need for completion TME, which is recommended in up to one third of cases,
8,
14,
15 and may be challenging. On the other hand, LE provides a histological proof of pCR, avoiding the delayed diagnosis of regrowth; in these patients long-term impact on survival is matter or debate.
20 In addition, while the watch-and-wait approach is only indicated in patients with clinical complete response, LE also seems appropriate in patients with a near complete clinical response. In the present study only 19 of 42 patients with a pCR were considered complete responders at restaging. Following the current indication (watch-and-wait to be performed only in patients with clinical complete response) 23 of 42 patients with pCR would have undergone TME instead of rectum preservation. An alternative approach could be to use both strategies within a rectum sparing program: watch-and-wait in patients with clinical complete response and LE in those with a near-complete clinical response. Independently from the strategy used, the key point still relies on the improvement of patient selection by better staging accuracy. As depicted in Fig.
1, in the group of patients with a pathologic major response (ypT0 and ypT1 with favorable histology) the rates of local recurrence were less than 5%, and more than 95% of patients were stoma-free with the rectum preserved.
The limitations of this study are related to the small sample size and to the lack of a comparative arm. Our institution is currently involved in a multicenter observational study (RESARCH), whose primary endpoint is to validate the rectal-sparing policy in patients with complete or near-complete clinical response after neoadjuvant chemoradiotherapy.
16 Randomized trials in this field are challenging mainly due to the difficult accrual of patients. Likely, the best evidence may therefore derive from large observational prospective trials or national and international registry.
21