Correspondence to: Simon Lundström (e-mail: Simon.Lundstrom@med.lu.se)
Department of Surgery
Skåne University Hospital
SE-214 21
Malmö, Sweden
_____
BJS, https://doi.org/10.1093/bjs/znae309, published 30 December 2024
_____
Dear Editor
We sincerely thank Chen et al. and Manenti et al. for their insightful comments on our study, which investigates the prognostic impact of the number of tumour deposits. We fully agree with Manenti et al. that further exploration of the pathogenesis and histopathological origins of tumour deposits is merited. Evidence suggests that tumour deposits represent a more aggressive metastatic pathway compared to the lymphatic dissemination seen in lymph-node positive cancer1. Notably, Lord et al. have even proposed that rectal cancer with lymph node involvement but without tumour deposits on preoperative MRI may serve as a protective prognostic factor, in stark contrast to tumour deposit-positive disease2.
Regarding Chen et al.’s concern about the limited prognostic value of tumour deposits in local recurrence, we concur that the relationship between tumour deposits and local recurrence appears to be weak. To address potential confounders and ensure the robustness of our findings, we conducted an extensive sensitivity analysis. Our results indicate that the prognostic effect of tumour deposits on local recurrence is largely attenuated when adjusting for other adverse histopathological features, such as perineural invasion, tumour grade, and lymphovascular invasion. This aligns with previous studies, where detailed subgroup analyses of rectal cancer patients have revealed a similar mitigation of the prognostic impact when accounting for other histopathological factors3. Given the effectiveness of current neoadjuvant and adjuvant treatment strategies, combined with the distinct metastatic pathway associated with tumor deposits, their influence on local recurrence is likely limited.
A major challenge in assessing local recurrence is the inherently low number of observed events, which hinders definitive conclusions. In our study, local recurrence was defined as “the recurrence of local extraperitoneal tumour, lymph node tumour growth, intraluminal tumour recurrence, or peritoneal tumour growth below the peritoneal reflection” in accordance with the Swedish Colorectal Cancer Registry. We recognize that this definition may cause some ambiguity but wish to clarify that “peritoneal tumour growth below the peritoneal reflection” only applies to local recurrences for rectal cancer. As such, we have adhered to established registry definitions of local recurrence but acknowledge that local recurrence remains prone to misclassification and, more importantly, underdiagnosis.
Once again, we appreciate the thought-provoking discussions raised by both groups and hope that ongoing research will continue to refine our understanding of tumor deposits and their role in colorectal cancer prognosis.
