Which tumour factors preclude organ preservation in patients with rectal cancer?

BACKGROUND: cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes, extramural vascular invasion (EMVI) and mesorectal fascia threatening (MRF+) have been utilized as exclusion criteria in several studies on the watch-and-wait (w&w) strategy. Here, our aim was to validate these criteria through a post hoc analysis of two pooled prospective studies on w&w following routine radio(chemo)therapy. METHODS: A review of baseline magnetic resonance imaging was performed in a subgroup of 223 patients treated at a single institution. Of these, 17.9 % started w&w, 12.6 % achieved clinical complete response (cCR) and 9.0 % sustained cCR during median follow-up of 54 months. RESULTS: The multivariable logistic analysis showed that the proportion of circumferential bowel involvement and EMVI significantly influenced the chance of sustained cCR; odds ratios were 0.063 (95 % confidence interval [CI] 0.008-0.489, p = 0.008), and 0.109 (95 % CI 0.014-0.850, p = 0.034), respectively. Sustained cCR was observed in none of the 57 patients with 90 %-100 % circumferential bowel involvement and in only one of the 89 patients with EMVI. In contrast, cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes or MRF+ were not independently associated with sustained cCR. Among the subgroups of patients with these features but without (near-)circular tumour or EMVI+, sustained cCR was observed in 12 %-25 % of patients. CONCLUSION: Sustained cCR after routine preoperative radio(chemo)therapy is unlikely in patients with (near-)circular tumour or EMVI, whereas patients with cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes and MRF+ should not be denied w&w.

The importance of measuring baseline tumour volume (or alternatively tumour length along with its rectal circumferential extent) in the watch-and-wait strategy in rectal cancer: a review.

BACKGROUND: The impact of the tumour volume or size on achieving clinical complete response (cCR) after radio(chemo)therapy is poorly understood. MATERIALS AND METHODS: A literature search was performed to gather data on the predictive value of baseline tumour volume or size in achieving cCR. RESULTS: In total, nine reports were identified. In two of three studies evaluating the baseline tumour volumetry, the tumour volume was the most powerful predictor for cCR. In four of six studies evaluating baseline tumour size without volumetry, tumour dimension was significantly associated with cCR, in one study reached borderline significance and in one report was insignificant. In three of four studies where a multivariable analysis was performed, the cT category did not show an independent predictive value for cCR. Because the tumour shape is often (semi)annular, its circumferential rectal extent along with the tumour length probably impact the tumour volume most, and thus, could be considered an acceptable alternative for time-consuming volumetry. CONCLUSIONS: Our review suggests that baseline tumour volume (or alternatively, tumour length along with its circumferential rectal extent) is the most relevant clinical predictor of cCR. Therefore, we postulate assessing and reporting these parameters in studies on the watch-and-wait strategy.

Correlation between Lymphocyte-to-Monocyte Ratio (LMR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Extramural Vascular Invasion (EMVI) in Locally Advanced Rectal Cancer.

Rectal cancer constitutes around one-third of all colorectal cancers. New markers are required to optimize the treatment. Extramural vascular invasion (EMVI) is a magnetic resonance imaging (MRI)-based negative prognostic marker. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) are blood-based systemic inflammatory response markers with proven prognostic value in many cancers, including CRC. We hypothesized whether there is a relationship between LMR, NLR, PLR and the presence of EMVI on pre-treatment MRI in patients with locally advanced rectal cancer (LARC). We conducted a retrospective analysis of 371 patients with LARC treated in the Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland between August 2016 and December 2021. One hundred eighty-four patients were found eligible for the study. A correlation between the extension of the tumour, nodal status, clinical stage of the disease and the presence of EMVI was found (p < 0.001). The pre-treatment level of neutrophils, platelets and carcinoembryonic antigen (CEA) was significantly higher in the EMVI-positive population (p = 0.041, p = 0.01, p = 0.027, respectively). There were no significant differences regarding the level of LMR, NLR and PLR between the EMVI-positive and EMVI-negative population. LMR, NLR and PLR do not differentiate patients in terms of EMVI; neither of these parameters is a good predictor of the status of EMVI in LARC.

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.