Watch-and-wait strategy in rectal cancer: Is there a tumour size limit? Results from two pooled prospective studies.

BACKGROUND: Frequency and predictive factors for a clinical complete response (cCR) in unselected patients are unclear. MATERIAL AND METHODS: Two prospective observational studies were designed and pooled to explore predictive factors for cCR. Both studies evaluated the watch-and-wait strategy in consecutive patients; the first single-institutional study in elderly with a small tumour, the second multi-institutional study in all the patients receiving standard of care preoperative radiotherapy. RESULTS: Four hundred and ninety patients were analysed. Short-course radiotherapy alone, or with consolidation chemotherapy or chemoradiation was given to 40.6%, 40.2% and 19.2% of the patients, respectively. The median interval from the radiation start to the first tumour response assessment was 10.2 weeks for short-course radiation and 13.2 weeks for chemoradiation. Seventy-three patients had cCR and 71 underwent w&w with the median follow-up of 24 months. The regrowth rate was 26.8%. cCR rate was 39.0% for low-risk cancer (cT1-2N0), 16.8% for intermediate-risk (cT3 with unthreatened mesorectal fascia [MRF-] or cT2N+) and 5.4% for high-risk (cT4 or MRF+). In the multivariable analysis, tumour volume (or tumour length and circumferential extent) and cN status were significant predictors for cCR. In circular cancers or with a length ≥7 cm (n = 184), cCR rate was only 2.7%, sustained cCR 1.6% and the sensitivity of cCR diagnosis 23.1%. None of 27 patients with a tumour larger than 120 cm3 achieved cCR. CONCLUSIONS: Considering watch-and-wait strategy is questionable in patients with circular tumours or with tumour length ≥7 cm.

Should Short-Course Neoadjuvant Radiation Therapy Be Applied for Low-Lying Rectal Cancer? A Systematic Review and Meta-Analysis of the Randomized Trials.

PURPOSE: National Comprehensive Cancer Network guidelines recommend either long-course chemoradiation (LC) or short-course radiation (SC, 5 × 5 Gy) for rectal cancer before total mesorectal excision. However, they do not recommend SC for low-lying tumors. As early toxicity of SC is lower than that of LC, and postoperative complications as well as late toxicity are similar, the probable reason is a notion that for low-lying tumors LC may be more effective than SC in assuring local control. METHODS AND MATERIALS: A systematic review and meta-analysis of the randomized trials comparing SC with LC was performed to test the hypothesis that for low-lying tumors, LC is superior to SC in reducing the risk of local failure. RESULTS: The systematic search identified 4 trials including, in total, 421 patients with tumors <5 cm from the anal verge; 221 were randomized to SC and 200 to LC. The meta-analysis showed that the difference in local failure rate between SC and LC was insignificant; the pooled odds ratio was 0.87, 95% confidence interval 0.53 to 1.44, P = .59. Heterogeneity between trials was insignificant; I2 = 0.0%, P = .47. CONCLUSIONS: Our meta-analysis does not support the notion that LC given before total mesorectal excision is superior to SC in reducing the risk of local failure in low-lying tumors.

The risk of distant metastases in rectal cancer managed by a watch-and-wait strategy - A systematic review and meta-analysis.

BACKGROUND: The watch-and-wait (w&w) strategy is associated with frequent local regrowth (LR). Distant metastases (DM) occur more often in the patients with LR than in those without. However, it is unknown whether omitting immediate surgery results in the additional risk of DM. MATERIALS/METHODS: A systematic review and meta-analysis were performed to determine the maximum risk of additional DM. To estimate this, we used data showing the proportions of DM in patients with and without LR, assuming that the excess DM in patients with LR may develop in two ways: from subclinical DM already present at baseline and due to seeding from the uncontrolled primary tumor, and that the incidence of subclinical DM at baseline in the LR subgroup is at least not lower than in the non-LR subgroup. Based on the calculated rate of excess DM in the LR subgroup we have obtained the rate for the whole group of patients undergoing w&w. RESULTS: The maximum estimated risk of additional DM was 3.0% (95% CI: 1.2-4.9%) in the total group. After correction for short follow-up, the maximum risk at 5 years was 6.5%. Thus, the risk of excess DM is between 0% and 6.5%. Other evidence from a systematic review and the conservative assumptions taken for the calculation of the correction suggest that this maximum risk may be overestimated. CONCLUSIONS: The additional risk of DM seems to be low. However, the high probability of bias, heterogeneity of the patients' population and low quality of evidence make our estimation uncertain.