Patients Diagnosed With Stage I to III Rectal Cancer at Younger Age Have Increased Risk for Positive Lymph Nodes

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Patients diagnosed with stage I to III rectal cancer at a younger age are at increased risk of having positive lymph nodes, according to an analysis of data published in the Journal of the National Cancer Institute. “This finding merits further investigation and may ultimately impact treatment decision-making for young early-stage patients,” concluded Joshua E. Meyer, MD, of Fox Chase Cancer Center, Philadelphia, and colleagues.

Using the Surveillance, Epidemiology, and End Results (SEER) database, investigators identified 56,076 patients, including 1,194 (2.1%) patients aged 20 to 39 years at diagnosis, and 4,199 (7.5%) patients aged 40 to 49 years, who were diagnosed with stage I to III rectal cancer between 1988 and 2008. These patients ≤ 49 years were defined as young. “Patients who received radiotherapy prior to surgery were excluded to eliminate the effect of preoperative radiation on lymph node harvest and positivity,” the researchers noted.

All patients in the study had a standard rectal cancer operation performed and at least one lymph node examined. “For patients in each T stage, lymph node positivity was inversely associated with age (all P < .001), ” the authors reported. “For T1, T2, and T3, age remained predictive of lymph node positivity status after adjustment for number of lymph nodes examined and other covariates (P < .001 for each stage).” These covariates included year of diagnosis, surgery type, grade, sex, and race. “Adjusted odds ratios for lymph node positivity for ages 20 to 39 vs 60 to 69 were: T1: 1.97 (95% confidence interval [CI] = 1.36–2.86); T2: 1.48 (95% CI = 1.13–1.95); T3: 1.30 (95% CI = 1.10–1.53).”

To further assess the impact of age, the investigators looked at the number of positive lymph nodes. In multivariate analysis, young age was found to be “a statistically significant predictor of an increased number of lymph nodes positive for stage T2 (P = .042) and T3 (P = .002).”

The finding that “younger patients have an increased risk of lymph node metastasis when examined within T stage cohorts,” according to the authors, “lends more support to the conclusion that rectal cancer in younger patients may have an increased predisposition for nodal metastasis.”

The investigators cautioned that their study “should not be interpreted as justification for a change in management of younger patients. However, it may be prudent to ensure that a thorough clinical investigation of lymph node–bearing regions is performed prior to surgical resection for younger patients. Additionally, these data may affect the preoperative workup for younger patients with early-stage disease being considered for local excision, as this procedure does not include lymph node dissection.”

Further Commentary

An editorial accompanying the study asserted that the results did have “significant clinical implications. Given the higher propensity amongst young rectal cancer patients to be occult lymph node positivity even for T1 disease, this will need to be taken into account for choice of surgical intervention,” wrote Joanne Ngeow, MBBS, MRCP, MPH, MD, of the Cancer Genetics Service at the National Cancer Centre, Singapore, and Charis Eng, MD, PhD, of the Genomic Medicine Institute at the Cleveland Clinic. “Although preoperative neoadjuvant chemoradiotherapy is recommended for the management of resectable rectal cancer, it is not uniformly practiced and the results here give further impetus for this to be standard of care in fit young rectal cancer patients.”

Meyer JE, et al: J Natl Cancer Inst 108(1):djv284, 2016 (early release online).

Ngeow J, Eng C: J Natl Cancer Inst 108(1):djv325, 2015 (early release online).