Opioid Use Disorder and Overdose Found to Be Rare but Significant After Stage II/III Colorectal Cancer Diagnosis

Opioid use disorder and overdose are important risks to consider in older patients diagnosed with stage II/III colorectal cancer, especially those who were opioid naïve.

Data from a retrospective cohort study indicated that opioid overdose was a rare but statistically significant outcome following diagnosis of stage II/III colorectal cancer (CRC) compared with noncancer, breast, and prostate cancer diagnoses among older patients, particularly patients who were opioid naïve.

Compared with matched noncancer controls, CRC diagnosis was associated with 71% higher odds of opioid use disorder (OUD) or nonfatal opioid overdose in the year following diagnosis (adjusted OR [aOR] 1.71; 95% CI, 1.28-2.29). The unadjusted rate of OUD or nonfatal overdose was 38.9 events per 10,000 patients in the CRC sample vs 25.2, 27.1, and 12.4 in the noncancer, breast, and prostate samples, respectively. CRC survivors were also more than twice as likely to experience nonfatal opioid overdose vs matched noncancer controls (aOR 2.33; 95% CI, 1.49-3.67).

“This study provides the first known estimates of the association between receipt of a common cancer diagnosis with subsequent OUD and opioid overdose…. Although these outcomes were rare, our finding that CRC survivors experienced elevated adjusted odds of opioid overdose is novel and informative,” the investigators wrote.

The study evaluated 69,889 survivors of breast (n = 31,346), prostate (n = 24,160), or colorectal (n = 14,383) cancer in comparison with matched noncancer controls (n = 125,007). The mean age ranged from 73 years to 76 years across all cohorts, and most assessed survivors were White. Approximately one-third of patients had a Charlson comorbidity score of more than 1. A moderate-to-high comorbidity burden affected nearly half of patients in the CRC cohort. Investigators observed a lower baseline prevalence of depression (6.0%) and anxiety (5.2%) in survivors of prostate cancer vs other survivor groups (depression range, 10.5%-12.2%; anxiety range, 9.1%-10.4%). Baseline nonopioid substance use disorders affected roughly 1% to 2% of assessed survivors, whereas other mental health conditions affected roughly 2% to 4%. A quarter of survivors experienced prior opioid use, with a mean daily milligram morphine equivalent of 37 mg.

When assessing outcomes in terms of other covariates, investigators found the risk of OUD and nonfatal overdose increased with age. Moreover, White race was associated with a 30% higher adjusted odds of the composite outcome (aOR 1.30; 95% CI, 1.01-1.68). Survivors with depression (aOR 1.98; 95% CI, 1.60-2.46), anxiety (aOR 1.28; 95% CI, 1.02-1.61), or a nonopioid substance use disorder (aOR 2.64; 95% CI, 1.95-3.57) all had significantly higher odds of OUD or overdose. Opioid-naïve patients who received a CRC diagnosis were over 4 times more likely to experience OUD or nonfatal overdose vs matched opioid-naïve noncancer controls (aOR 4.22; 95% CI, 2.65-6.71). Additionally, patients with more than 90 days of opioid use in the 6 months before index had higher adjusted odds of OUD or overdose vs those with no prior use (aOR 19.26; 95% CI, 15.14-24.49); among those with prior opioid use, there was no significant difference in outcomes between survivors of cancer and matched noncancer controls.

“Given the concerning association between a CRC diagnosis and opioid overdose in older adults, providers may consider incorporating evidence-based opioid risk–screening tools and naloxone coprescribing into their care of these patients. Additionally, screening this population for depression and suicide risk may be advisable,” investigators concluded.

The most prominent limitation of the study was the sampling, and investigators cautioned that these findings are not generalizable to other cancer types, metastatic cancers, or younger survivor groups. Moreover, as the study only examined Medicare beneficiaries, these findings may not be reproduceable in other payer groups. Nonetheless, these data demonstrate the importance of considering opioid overdose risks in clinical settings following CRC diagnoses.


Roberts AW, Eiffert S, Wulff-Burchfield EM, Dusetzina SB, Check DK. Opioid use disorder and overdose in older adults with breast, colorectal, or prostate cancer. J Natl Cancer Inst. 2021;113(4):425-433. doi:10.1093/jnci/djaa122