Overuse and Limited Benefit of Chemotherapy for Stage II Colon Cancer in Young Patients

Birkett, Richard; Chamely, Elias; Concors, Seth J.; Bleier, Joshua I. S.; Aarons, Cary B.; Shanmugan, Skandan; Saur, Nicole M.; Paulson, Emily Carter

doi:10.1016/j.clcc.2019.04.002

Cited by 21 publications

(11 citation statements)

References 24 publications

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“…Another limitation of the present work is the unexpected low rate of MSI‐high colon cancers in the study population (7.5% and 8.8% in the adjuvant chemotherapy and observation group, respectively), while MSI phenotype is known to account for 12% to 20% of colon cancers in Western countries 42 . MSI status is probably underreported given present MSI rates are in line with previous NCDB publications 43 …”

Section: Discussionmentioning

confidence: 62%

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Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database

Achilli

Crippa

Grass

et al. 2020

Intl Journal of Cancer

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Utility of adjuvant chemotherapy for stage II cancer remains a matter of debate. Clinical guidelines suggest adjuvant chemotherapy for stage II tumors with high-risk features, in particular T4 tumors. However, limited consensus exists regarding the importance of other high-risk features (lymphovascular or perineural invasion, microsatellite instability). Our study aimed to investigate the impact of adjuvant chemotherapy for stage IIA (T3N0) colon cancer patients. Patients who underwent colectomy for stage IIA colon adenocarcinoma (2010-2015) were identified in the National Cancer Database (NCDB) and divided in two groups based on receipt of adjuvant chemotherapy vs observation. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed to compare overall survival between the two groups. Subgroup analysis of patients with specific high-risk features LVI, PNI and MSI was performed. Among 46 688 surgical patients with stage IIA colon adenocarcinoma 5937 (12.7%) received adjuvant chemotherapy, while 40 751 (87.3%) were observed. Five-year IPTW-adjusted survival was higher in the adjuvant chemotherapy group (79.7% [95% CI 79.1, 80.2]) compared to the observation group (70.3% [95% CI 69.7, 70.9]). Patients with high-risk pathological features showed an estimated 5-year survival benefit of 11.3% (78.2% [95% CI 77.4, 79.1] vs 66.9% [95% CI 65.9, 67.8]) when treated with adjuvant chemotherapy. This NCDB analysis revealed a survival benefit for patients with stage IIA colon adenocarcinoma and high-risk features that were treated with adjuvant chemotherapy.

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Section: Discussionmentioning

confidence: 62%

“…42 MSI status is probably underreported given present MSI rates are in line with previous NCDB publications. 43…”

Section: Discussionmentioning

confidence: 99%

Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database

Achilli

Crippa

Grass

et al. 2020

Intl Journal of Cancer

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“…Patients with stage II colorectal cancer (CRC) have a relatively good prognosis, with an approximate 5 year overall survival rate of 90% . Although radical surgery is the primary therapy for patients with stage II CRC, adjuvant chemotherapy (ACT) is often recommended for patients with one or more clinical high risk factors, including T4 invasion, poor differentiation, lymphovascular invasion, perineural invasion, perforation, obstruction, insufficient node samples (less than 12), etc. − However, current studies have shown discrepant results in preventing recurrence for patients with stage II CRC who received ACT after surgery. − Furthermore, not all patients with stage II CRC with one or more of these factors benefitted from ACT. ,− Thus, the traditional anatomy-based clinical risk factors are insufficient for predicting recurrence and have led to unnecessary chemotherapy-related toxicities for patients with low recurrent risk, indicating the necessity of developing novel biomarkers to stratify patients into groups most likely to benefit from ACT or those in whom ACT was toxic. − …”

Section: Introductionmentioning

confidence: 99%

Predictive Value of Circulating Tumor Cells Based on Subtraction Enrichment for Recurrence Risk in Stage II Colorectal Cancer

Chen

Zhang

et al. 2022

ACS Appl. Mater. Interfaces

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Current guidelines recommend adjuvant chemotherapy (ACT) for stage II colorectal cancer (CRC) patients by using clinical high risk factors, with which circulating tumor cells (CTCs) were not considered. Here, an assessment to detect CTCs based on subtraction enrichment mediated by magnetic beads conjugated with CD45, immunofluorescence staining of CK, and fluorescence in situ hybridization of CEP8 is established. Both CEP8- and CK-positive CTCs have the potential to improve the risk stratification of stage II CRC patients. Patients with preoperative CTCs of ≥4 had a significantly higher recurrence risk than those with preoperative CTCs of <4 in two external validation cohorts (P < 0.0001). In the subgroup with clinical high risk, when preoperative CTCs were <4, patients did not benefit from ACT (P = 0.5764); however, when preoperative CTCs were ≥4, patients received benefit from ACT (P = 0.0064). Additionally, regardless of clinical risk status and preoperative CTC levels, if postoperative CTC levels were ≥4 for more than three consecutive time points (monitoring time interval, 2–6 months), the recurrence rate was 100%. Our findings suggested that the subtraction enrichment of CTCs could provide a reliable method to stratify the recurrence risk and make therapeutic decisions after surgery in stage II CRC patients.

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“…[ 12 , 13 ] Although adjuvant chemotherapy remains controversial in stage II CRC, most stage IIB and IIC diseases still require chemotherapy, whether oral or intravenous. [ 14 , 15 ]…”

Section: Introductionmentioning

confidence: 99%

“…[12,13] Although adjuvant chemotherapy remains controversial in stage II CRC, most stage IIB and IIC diseases still require chemotherapy, whether oral or intravenous. [14,15] Most studies indicated inadequate LNH (< 12) in stage II disease as a poor survival factor, and some studies discussed the optimal LNH number for stage II CRC [7,8,16] ; however, few studies have demonstrated the impact of low LNH number on survival in stage IIB and IIC disease. This study aimed to identify the influence of insufficient number of LNH on survival among stage IIB and IIC CRC patients.…”

Section: Introductionmentioning

confidence: 99%

Impact on inadequate lymph node harvest on survival in T4N0 colorectal cancer: A would-be medical center experience in Taiwan

et al. 2022

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Insufficient lymph node harvest (< 12) may lead to incorrect classification of stage I and II disease. Many studies have indicated a poor prognosis with inadequate lymph node harvest in stages I to III, but few studies have demonstrated the relationship between low lymph node harvest and T4 disease. This study aimed to identify the influence of insufficient number of lymph nodes harvested on survival in T4N0 colorectal cancer. We enrolled patients with T4N0 colorectal cancer who underwent radical resection between 2010 and 2016. A total of 155 patients were divided into 2 groups; 142 patients had ≥ 12 harvested lymph nodes, and the other 13 had < 12 lymph nodes. All patients were followed up for at least 5 years. The primary outcome was the impact of the number of lymph nodes harvested on disease-free survival and overall survival, which were investigated using Kaplan-Meier survival techniques. There were no significant differences in recurrence rate, emergent or elective surgery, laparoscopic or open surgery, or chemotherapy between the 2 groups. Kaplan-Meier analyses showed no statistical differences in 5-year disease-free survival ( P = .886) and 5-year overall survival ( P = .832) between the groups. There were no significant differences in disease-free survival and overall survival between patients with adequate (≥ 12) and inadequate (< 12) lymph node harvest in T4N0 colorectal cancers.

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Overuse and Limited Benefit of Chemotherapy for Stage II Colon Cancer in Young Patients

Cited by 21 publications

References 24 publications

Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database

Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database

Predictive Value of Circulating Tumor Cells Based on Subtraction Enrichment for Recurrence Risk in Stage II Colorectal Cancer

Impact on inadequate lymph node harvest on survival in T4N0 colorectal cancer: A would-be medical center experience in Taiwan

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