December's Paper of the Month is looks at a study which assessed the impact of tumour deposits on oncological outcomes.
Tumour deposits in colon cancer predict recurrence and reduced survival in a nationwide population-based study
Jörgren F, Agger E, Lydrup ML, Buchwald P
BJS Open 2023 Nov 1;7(6):zrad122. doi: 10.1093/bjsopen/zrad122.
What is known about the subject?
Tumor deposits (TD) in colon cancer are defined as tumor foci in the pericolic fat, distant from the tumor invasion front in the lymphatic drainage territory of the tumour, without recognizable residual lymph node tissue [1]. Tumour deposits within a vessel wall should be considered lymphovascular invasion (L+), vascular invasion (V+) for deposits in spaces lined by endothelial cells with associated red blood cells or smooth muscle cells, and perineural invasion (Pn+) when tumour nodules are found around a neural structure [1].It is worth noting that the definition of TDs has changed from the 7th to the 8th TNM classification, namely from "no evidence of residual lymph nodes in the nodule" to "or recognisable vascular or neural structures". Which means that nowadays, only nodules containing no identifiable lymph node tissue or vascular/neural structures are considered tumour deposits and labelled N1c [2].
However, in an analysis of The US National Cancer Database in 6424 cases of colon cancer, patients with tumor deposits received less robust lymph node harvesting - a known risk factor for worse outcome and undertreatment - and were less likely to receive adjuvant therapy (52% versus 74% of patients with LN-positive tumors; p < 0.0001) [3].
Most data are published based on retrospective evaluations and focus on overall survival and much less on local recurrence. The exact prevalence of tumor deposits and the subsequent risk of local recurrence of colon cancer is not well known.
Since 2007, all patients in Sweden with adenocarcinoma of the colon have been registered in the Swedish Colorectal Cancer Registry (SCRCR), a nationwide quality registry that has registered 70,499 patients with colon cancer to date. In 2011, TDs were included in the SCRCR dataset [4].
The study is population-based and aimed to assess the impact of TDs on rates of local recurrence (LR) and distant metastasis (DM), as well as overall and relative survival in colon cancer [5]. The secondary aims were to perform subgroup analyses of the prognostic value of TDs in different N stages and in patients with LNMs. It is a retrospective analysis of prospectively registered data of patients with colon cancer registered in the SCRCR between 1 January 2011 and 31 December 2014. Included in the final analysis were patients with TNM stage I–III disease who underwent R0 abdominal resection surgery (hemicolectomies/ colectomies) and were alive 90 days after surgery with a registered 5-year follow-up.
What the study adds?
A total of 8014 patients with colon cancer could be analysed. 808 of them were TD-positive and 7206 TD-negative, which corresponds to a rate of 10.1 patients with TD.
Patients with TD positive tumours had a higher T and N stage, tumour grading and incidence of lymphovascular and perineural invasion; they were younger and had more often left-sided tumours.
Compared to TD negative patients, TD-positive patients received more often adjuvant chemotherapy. However, they received less chemotherapy than nodal-positive patients did. Among N1c patients, 41.8% received adjuvant chemotherapy, compared to 53.8% for N1a, 60.8% for N1b, 65.5% for N2a and 67.4% for N2b patients (p < 0.001).
The local recurrence rate was higher in TD-positive compared to TD-negative patients (7.2 versus 3.0%; p< 0.001). Metachronous distant metastasis were recorded in 1138 patients (14.2%), with a higher frequency among TD-positive patients (33.9 versus 12.0%; p < 0.001).
In multivariable Cox regression analysis, a TD-positive tumour was an independent risk factor for both local recurrence (HR 1.50, 95% c.i. 1.09 to 2.07; p = 0.013) and distant metastasis (HR 1.91, 95% c.i. 1.64 to 2.23; p < 0.001).
The 5-year overall survival rate for patients with TD-positive tumours was significantly lower at 56.8% compared to 74.9% for patients with TD-negative tumours (p < 0.001).
In multivariable Cox regression analysis, a TD-positive tumour was again an independent risk factor for decreased overall (HR 1.60, 95% c.i. 1.40 to 1.82; p < 0.001) and relative (EHR 2.24, 95% c.i. 1.81 to 2.78; p < 0.001) survival.
Implications for colorectal practice
Although guidelines recommend adjuvant chemotherapy for patients with stage III colon cancer, N1c patients receive less chemotherapy than other stage III patients. Furthermore, some patients with N1c tumours in the study could be downgraded to stage II N0 according to the eighth edition of the TNM classification. This current study shows an independent prognostic value of TDs across all N-stages and independent of the presence of LNMs, which are partially ignored by the current TNM staging system.
Take home message
When discussing adjuvant chemotherapy at postoperative MDTs, it is important to recognise the negative prognostic impact of TDs in colorectal cancer.
References
- Weiser MR. AJCC 8th Edition: Colorectal Cancer. Ann Surg Oncol (2018) 25:1454–1455. doi.org/10.1245/s10434-018-6462-1.
- Delattre JF, Oguz Erdogan AS, Cohen R, Shi Q, Emile JF, Taieb J, Tabernero J, André T, Meyerhardt JA. Nagtegaal ID, Svrcek M. A comprehensive overview of tumour deposits in colorectal cancer: Towards a next TNM classification. Cancer Treat Rev 2022 Feb:103:102325. doi: 10.1016/j.ctrv.2021.102325.
- Mirkin K, Kulaylat AS, Hollenbeak CS, Messaris E. Prognostic Significance of Tumor Deposits in Stage III Colon Cancer. Ann Surg Oncol (2018) 25:3179–3184. https://doi.org/10.1245/s10434-018-6661-9
- Regional Cancer Centres of Sweden. Annual Report from the Swedish Colorectal Cancer Registry; 2021. https://www.cancercentrum.se/samverkan/cancerdiagnoser/tjocktarm-andtarm-och-anal/tjock-och-andtarm/kvalitetsregister
- Jörgren F, Agger E, Lydrup ML, Buchwald P. Tumour deposits in colon cancer predict recurrence and reduced survival in a nationwide population-based study. BJS Open 2023 Nov 1;7(6):zrad122. doi: 10.1093/bjsopen/zrad122.
