Poorer Oncologic Outcome of Good Responders to PCRT With Remnant Lymph Nodes Defies the Oncologic Paradox in Patients With Rectal Cancer

Abstract

Prognostic impact of metastatic lymph nodes should be carefully considered in deciding treatment plan after preoperative chemoradiotherapy (PCRT). The decision to withhold patients from complete local control by total mesorectal excision after PCRT needs to be made with caution: nodal positivity, not readily detectable with tools currently used in clinical staging, could be more lethal than it was previously believed in patients with rectal cancer that have not undergone PCRT. Introduction: We evaluated the oncologic outcome of (y)pT0-2Nþ rectal cancer and investigated the impact of metastatic lymph nodes (LNs) on oncologic outcome in the setting of preoperative chemoradiotherapy (PCRT). Materials and Methods: The records of 1403 patients who underwent surgery for rectal cancer between January 2005 and December 2012 were analyzed. The patients were categorized according to the pathologic stage, including 728 patients with ypT0-2 and 675 with ypT3-4 disease. The oncologic outcomes in terms of the 5-year recurrence-free survival (RFS) and overall survival (OS) were analyzed. Results: Metastatic LNs were observed in 11.5% (n ¼ 84) of patients with ypT0-2 and 42.9% (n ¼ 290) of patients with ypT3-4 disease. The RFS and OS were stratified according to ypT and ypN stage as ypT0-2N0, T0-2Nþ, T3-4N0, and T3-4Nþ. The ypT0-2Nþ group had slightly lower RFS and OS than those in the ypT3-4N0 group. LN metastasis was significantly associated with RFS in both ypT0-2 and ypT3-4 disease, with a stronger association for ypT0-2 disease (hazard ratio, 3.473, 95% confidence interval, 2.058-5.261; P < .001 for ypT0-2 and hazard ratio, 2.038; 95% confidence interval, 1.601-2.684; P < .001 for ypT3-4, respectively). Conclusion: The oncologic outcomes of ypT0-2Nþ disease were not favorable compared with those of ypT3-4N0 disease. These outcomes dispute the survival paradox traditionally believed for non-PCRT-treated patients with rectal cancer, and highlight the underestimated significance of post-PCRT nodal involvement. The prognostic importance of metastatic LNs should be considered when deciding the surgical strategy after PCRT. Further studies including larger numbers of patients with sufficient follow-up are needed to verify the oncologic impact of metastatic LNs within tumors contained within the bowel wall after PCRT.

Retrospective survival analysis of stage II–III rectal cancer: tumour regression grade, grading and lymphovascular invasion are the only predictors

“…Surprisingly enough, lymph node status and LNR were not related to prognosis (either OS or DFS) in our series, as node‐positive and node‐negative tumours resulted as having, for example, the same OS (75.0 versus 75.5 months, respectively). Indeed, the impact of node metastasis on rectal cancer prognosis is a matter of debate 25–32 . On one hand, the presence of metastatic lymph nodes is considered one of the most significant predictor of short DFS and OS in patients affected by rectal cancer without distant metastasis 24–27 .…”

“…Indeed, the impact of node metastasis on rectal cancer prognosis is a matter of debate 25–32 . On one hand, the presence of metastatic lymph nodes is considered one of the most significant predictor of short DFS and OS in patients affected by rectal cancer without distant metastasis 24–27 . In this regard, LNR is reportedly also an independent prognostic factor in such a population, regardless of the total number of examined lymph nodes 29 .…”

“…In this regard, LNR is reportedly also an independent prognostic factor in such a population, regardless of the total number of examined lymph nodes 29 . According to Cho et al ., patients with yp T0–2 disease and lymph node metastases show a worse prognosis compared to yp T3–4 without lymph node metastases, even in patients with complete tumour regression 27 . This result could be explained by the presence of a subset of patients with more aggressive disease, the early tendency to node metastatization and chemoradio‐resistance of lymph node metastases 27 …”

A Nine-Gene Signature for Predicting the Response to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer

“…Preoperative chemoradiotherapy (PCRT) followed by surgical resection is the standard multimodal treatment for LARC [3,4]. Around 30% of the total patients show a complete response to this treatment, having better long-term oncologic results and local control [5][6][7][8][9][10][11]. PCRT decreases the risk of local recurrence and increases the possibility of sphincter preservation.…”