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

BACKGROUND: Few studies have confirmed a benefit for adjuvant chemotherapy (aCTX) in stage II colon cancer. We used the National Cancer Database to explore the use and efficacy of aCTX in patients with both normal-risk (NR) and high-risk (HR) young stage II colon cancer. PATIENTS AND METHODS: We identified patients with stage II colon cancer who underwent colectomy between 2010 and 2015. HR patients included at least: lymphovascular or perineural invasion, < 12 lymph nodes, poor/un-differentiation, T4, or positive margins. Rates of aCTX by age and risk were calculated, and adjusted factors associated with aCTX were identified. Overall survival was estimated using the Kaplan-Meier method and Cox multivariable analyses for patients < 50 years. RESULTS: Among the 81,066 stage II patients who underwent colectomy, 6093 (7.5%) were < 50 years old. Of these, 2669 patients were HR. Thirty percent of NR and almost 60% of HR patients < 50 years received aCTX, compared with 8% and 23% of patients > 50 years (P < .001). In NR patients < 50 years, 35.3% with microsatellite-stable tumors and 18% with microsatellite unstable tumors received aCTX (P < .001), whereas 63.6% and 43.2%, respectively, of HR patients did (P < .001). The most significant multivariable predictors of aCTX were risk status and age. On univariate analysis, there was no survival benefit associated with aCTX in patients < 50 years. Multivariate analysis failed to demonstrate a survival benefit for aCTX for either group (HR, 0.97; P = .84; NR, 0.1.03; P = .90). CONCLUSION: Young patients with HR and NR colon cancer received aCXT more frequently than older patients with no demonstrable survival benefit. This bears further evaluation to avoid the real risks of over-treatment in this increasing population.

Combined Proctectomy and Hepatectomy for Metastatic Rectal Cancer Should be Undertaken with Caution: Results of a National Cohort Study.

BACKGROUND: Simultaneous proctectomy and hepatic resection for stage IV rectal cancer remains controversial due to concerns for increased morbidity and mortality. While small series have described simultaneous rectal and hepatic resection, surgical outcomes in a large national cohort have not been described. METHODS: Overall, 9012 patients with stage IV rectal adenocarcinoma with hepatic metastases were identified in the National Cancer Data Base (2010-2015). Associations between treatment selection, tumor and patient characteristics, 30- and 90-day mortality, and factors predictive of survival after surgery were examined. Logistic regression analyses were used to evaluate associations between tumor/patient characteristics, and selection of combined proctectomy and hepatectomy (C-PH). Kaplan-Meier analysis was used to identify median survival stratified by age and other patient-specific factors. RESULTS: Among patients included for analysis, 1331 (14.8%) underwent C-PH. Factors associated with lower rates of C-PH included increasing age, Black/Hispanic race, increased Charlson comorbidity score, Medicare/Medicaid/uninsured status, and treatment at a community cancer program. Thirty- and 90-day mortality increased with age (Chi square 11.4, p < 0.005; and Chi square 23.9, p < 0.001, respectively). On multivariate analysis, poorer survival after C-PH was associated with age > 70 years (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.0-2.5, p < 0.001), perineural invasion (HR 1.5, 95% CI 1.2-1.9, p < 0.001), kras mutation (HR 1.5, 95% CI 1.1-2.1, p = 0.006), positive circumferential margin (HR 1.3, 95% CI 1.0-1.7, p = 0.03), and omission of postoperative chemotherapy (HR 1.4, 95% CI 1.1-1.7, p = 0.002). CONCLUSIONS: C-PH should be utilized with caution in frail, high-risk patients. Such patients may be better served by staged surgical management or nonsurgical therapy.

Elective colon resection without curative intent in stage IV colon cancer.

BACKGROUND: Evidence suggests that elective primary colon resection (ePCR) in patients with asymptomatic colon tumors and unresectable metastases is not required and may expose patients to unnecessary operative risk. METHODS: Stage IV colon cancer patients with liver metastases from 2000 to 2011 were identified with SEER-Medicare data. Liver-based therapy or urgent/emergent colectomies were excluded. Chemotherapy alone was compared to ePCR ±â€¯chemotherapy. Univariate and multivariate analyses were used to identify predictors of ePCR. Multivariate Cox regression compared survival. RESULTS: 5139 patients were identified. The ePCR rate decreased over time; 84% underwent ePCR in 2000, compared to 52% in 2011 (p < 0.001). In multivariate analysis, older patients were more likely to undergo ePCR, as were patients from rural areas (OR 1.65, p < 0.001). The odds of PCR in high poverty areas (>10%) were almost 25% higher than those in low poverty areas (OR 1.23, p = 0.03). African-Americana were less likely to undergo PCR than Caucasians (OR 0.76, p = 0.01). In multivariate survival analysis, PCR was associated with a significant survival benefit (HR 0.59, p < 0.001). CONCLUSIONS: Although ePCR is not recommended with unresectable metastases and the rate has decreased significantly, over 50% of patients with untreated hepatic metastases underwent ePCR in 2011. Disparities exist in use of ePCR that are likely multifactorial and deserve further study.

A preoperative prediction model for risk of multiple admissions after colon cancer surgery.

BACKGROUND: A subset of patients who undergo colon cancer surgery may be at a high risk of multiple subsequent admissions. We developed a simplified model to predict the preoperative risk of multiple postoperative admissions (MuAdm) among patients undergoing colon resection to aid in preoperative planning. METHODS: Patients aged ≥18 y with colon cancer who underwent elective surgical resection identified in discharge claims from California and New York (2008-2011) were included. The primary outcome, MuAdm, was defined as 2 or more admissions in the year following resection. Logistic regression models were developed to identify factors predictive of MuAdm. A weighted point system was developed using beta-coefficients (P < 0.05). A random sample of 75% of the data was used for model development, which was validated in the remaining 25% sample. RESULTS: A total of 14,780 patients underwent colon resection for cancer. Almost 30% had an admission in the year after index surgery and 9.8% had MuAdm. The significant predictors of MuAdm were higher Elixhauser comorbidity index score, metastatic disease, payer system, and the number of admissions in the year before surgery. Scores ranged from 0 to 8. Scores ≤1 had a 7% risk of MuAdm, and scores ≥6 had a >30% risk of MuAdm. CONCLUSIONS: In the year following discharge after resection of colon cancer, nearly 10% of patients are admitted 2 or more times. A simple, preoperative clinical model can prospectively predict the likelihood of multiple admissions in patients anticipating resection. This model can be used for preoperative planning and setting postoperative expectations more accurately.

Factors affecting local regrowth after watch and wait for patients with a clinical complete response following chemoradiotherapy in rectal cancer (InterCoRe consortium): an individual participant data meta-analysis.

BACKGROUND: In patients with rectal cancer who achieve clinical complete response after neoadjuvant chemoradiotherapy, watch and wait is a novel management strategy with potential to avoid major surgery. Study-level meta-analyses have reported wide variation in the proportion of patients with local regrowth. We did an individual participant data meta-analysis to investigate factors affecting occurrence of local regrowth. METHODS: We updated search results of a recent systematic review by searching MEDLINE and Embase from Jan 1, 2016, to May 5, 2017, and used expert knowledge to identify published studies reporting on local regrowth in patients with rectal cancer managed by watch and wait after clinical complete response to neoadjuvant chemoradiotherapy. We restricted studies to those that defined clinical complete response using criteria equivalent to São Paulo benchmarks (ie, absence of residual ulceration, stenosis, or mass within the rectum on clinical and endoscopic examination). The primary outcome was 2-year cumulative incidence of local regrowth, estimated with a two-stage random-effects individual participant data meta-analysis. We assessed the effects of clinical and treatment factors using Cox frailty models, expressed as hazard ratios (HRs). From these models, we derived percentage differences in mean θ as an approximation of the effect of measured covariates on between-centre heterogeneity. This study is registered with PROSPERO, number CRD42017070934. FINDINGS: We obtained individual participant data from 11 studies, including 602 patients enrolled between March 11, 1990, and Feb 13, 2017, with a median follow-up of 37·6 months (IQR 25·0-58·7). Ten of the 11 datasets were judged to be at low risk of bias. 2-year cumulative incidence of local regrowth was 21·4% (random-effects 95% CI 15·3-27·6), with high levels of between-study heterogeneity (I2=61%). We noted wide between-centre variation in patient, tumour, and treatment characteristics. We found some evidence that increasing cT stage was associated with increased risk of local regrowth (random-effects HR per cT stage 1·40, 95% CI 1·00-1·94; ptrend=0·048). In a subgroup of 459 patients managed after 2008 (when pretreatment staging by MRI became standard), 2-year cumulative incidence of local regrowth was 19% (95% CI 13-28) for stage cT1 and cT2 tumours, 31% (26-37) for cT3, and 37% (21-60) for cT4 (random-effects HR per cT stage 1·50, random-effects 95% CI 1·03-2·17; ptrend=0·0330). We estimated that measured factors contributed 4·8-45·3% of observed between-centre heterogeneity. INTERPRETATION: In patients with rectal cancer and clinical complete response after chemoradiotherapy managed by watch and wait, we found some evidence that increasing cT stage predicts for local regrowth. These data will inform clinician-patient decision making in this setting. Research is needed to determine other predictors of a sustained clinical complete response. FUNDING: None.

Location and timing of care for colon cancer patients in the VA Health System.

BACKGROUND: We sought to identify colon cancer patients within the Veterans Affairs (VA) system who experienced lengthy wait times for surgery or chemotherapy. We looked specifically at the relationship between location of treatment and timing of care. METHODS: We performed a retrospective cohort study of 4635 patients diagnosed with colon cancer in the VA Health System during 2002-2010 and treated with surgery followed by chemotherapy. We used VA administrative databases, including the VA Outpatient Clinic, Patient Treatment, and Fee Basis inpatient and outpatient files. Time from diagnosis to surgery and time from surgery to initiation of chemotherapy were the primary outcome measures. RESULTS: Patients who required referral to a hospital different from their home VA facility for surgery experienced delays in surgical intervention compared with patients treated at their home VA medical center. For patients referred outside of the VA system, this delay was almost 2 wk (13.5 d, P < 0.001). When these patients then went to another hospital for chemotherapy, they experienced further delays in care. Patients treated surgically outside the VA system who returned to the VA system for chemotherapy were more likely to initiate chemo >8 wk following surgery (OR 1.69, P = 0.01). The average adjusted time from surgery to chemotherapy for these patients compared with those treated wholly within the VA system was 11.4 d (P = 0.003). CONCLUSIONS: VA patients who require treatment at multiple hospitals for colon cancer, especially those who require surgery outside of the VA system, are more likely to experience delays in care compared with patients treated at a single hospital.

National Cancer Institute designation predicts improved outcomes in colorectal cancer surgery.

BACKGROUND: Although National Cancer Institute (NCI) designation as a cancer center is based almost solely on research activities, it is often viewed, by patients and referring providers, as an indication of clinical excellence. OBJECTIVE: To compare the short- and long-term outcomes of colon and rectal cancer surgery performed at NCI-designated centers to the outcomes after resection at non-NCI-designated hospitals. METHODS: We performed a retrospective cohort study of Survival, Epidemiology, and End Results (SEER)-Medicare database patients undergoing segmental colectomy (n = 33,969) or proctectomy (n = 8591) for cancer from 1996-2003. Multivariate logistic regression, with and without propensity scores, and matched conditional regression were performed to evaluate the relationship between NCI status and postoperative mortality (in-hospital or 30-day death). The log-rank test, Kaplan-Meier curves, and Cox regression compared survival between hospital types. RESULTS: We evaluated 33,969 colectomy and 8591 proctectomy patients. Postoperative mortality after colectomy was 6.7% at non-NCI and 3.2% at NCI centers. Mortality after proctectomy was 5.0% and 1.9%, respectively. These differences were significant when adjusted for patient and hospital characteristics. For both colon and rectal cancer patients, long-term mortality was significantly improved after resection at NCI centers (HR 0.84, P < 0.001; HR 0.85, P = 0.02, respectively). CONCLUSION: NCI designation is associated with lower risk of postoperative death and improved long-term survival. Possible factors responsible for these benefits include surgeon training, multidisciplinary care, and adherence to treatment guidelines. Studies are underway to elucidate the factors leading to improved patient outcomes.