Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer

Abstract

Purpose Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy ([C]RT) have improved local control of rectal cancer; however, we have been unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs. Patients and Methods Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features. Results On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042). Conclusion LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.

Prognostic impact of residual lateral lymph node metastasis after neoadjuvant (chemo)radiotherapy in patients with advanced low rectal cancer

“…Although patients with LLNs had a better outcome than those with mesorectal ypN2+ disease, a previous multi-institutional study 2 from Japan showed that the survival rate of patients with LLN metastasis was similar to that of patients with pN2 status when neoadjuvant (C)RT was not performed. Importantly, LLND was highly standardized in the present series with en bloc lymphadenectomy; a previous study 15 in this field showed little benefit from limiting resection to the affected LLNs, as more than half of the patients later developed local recurrence in the same compartment.…”

“…Similar data have been reported from the West, with a recent study finding a lateral local recurrence rate of 33·3 per cent at 4 years when LLNs had a short‐axis diameter of 10 mm or above. A recent multi‐institutional international retrospective study from 12 institutions reported that patients with LLNs and a short‐axis diameter of at least 7 mm had a significantly higher risk of lateral local recurrence than patients with LLNs of less than 7 mm. In addition, a recent survey showed that most radiation oncologists in the USA treat involved LLNs with curative intent and recommend treatment intensification, in the form of LLND, radiotherapy boost, or both.…”

“…In contrast, in Western countries, neoadjuvant (C)RT protocols are mostly employed, resulting in local recurrence rates of less than 10 per cent, with minimal indication for LLND. Recently, however, Eastern and Western studies have suggested that (C)RT and TME without LLND may not be sufficient in patients with enlarged LLNs, with a lateral pelvic recurrence rate of 19·5 per cent in patients with LLNs 7 mm or more in size.…”

Fibronectin in Cancer: Friend or Foe

“…In the very early stage of tumor progression, FN is downregulated to help tumor cells ameliorate their oncogene-or loss of TSG-induced endogenous ER stresses and evade senescent limitation of cell cycle progression. Therefore, for tumor patients in a very early clinical stage, in addition to the traditional surgery, chemotherapies, and radiotherapies or recently prevailing immune checkpoint blockade therapies [353][354][355], therapeutic strategies can be formed by inducing overexpression of FN in newly transformed tumor cells and force tumor cells into senescent state or cell cycle arrest followed by cell apoptosis, if FN is proved to be a regulator for senescent induction by enhancing ER stresses. Alternatively, tumor senescence and subsequently apoptosis can be induced circumventing alteration of FN expression level [356,357].…”

Significance of lymph node involvement in local recurrence of colorectal cancer

“…This finding supports the need for a careful analysis of LN+ during the pretherapeutic and per‐operative period to perform a complete resection. The rate of lymphatic spread with LR is inconsistent in the literature because LN recurrence and LR are frequently defined as a similar disease . Among series defining nodal and LR as two distinct diseases, the association of LN+ plus LR ranges from 1.8% to 87.5% …”