4-week treatment delay ups mortality in cancer patients

A 4-week delay in cancer treatment can increase mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers, with longer delays being more and more harmful to patients, suggest the results of a systematic review and meta-analysis.

“Policies focused on minimizing system level delays to cancer treatment initiation could improve population level survival outcomes,” the researchers said.

Medline was searched from 1 January 2000 to 10 April 2020 for published studies focusing on curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck. The hazard ratio (HR) for overall survival (OS) for each 4-week delay for every indication was the main outcome.

The researchers measured delay from diagnosis to first treatment or from the completion of one treatment to the start of the next. Their primary analysis included only high-validity studies controlling for major prognostic factors. HRs were assumed to be log linear with regard to OS and were converted to an effect for each 4-week delay. DerSimonian and Laird random effect models were used to estimate pooled effects.

Thirty-four studies for 17 indications, including a total of 1,272,681 patients, were eligible for the review. High-validity data were not found for five of the radiotherapy indications or for cervical cancer surgery. Thirteen of these indications showed a significant association between delay and increased mortality (p<0.05). [BMJ 2020;371:m4087]

Findings for surgery were consistent, with a mortality risk of 1.06–1.08 (eg, colectomy: HR, 1.06, 95 percent confidence interval [CI], 1.01–1.12; breast surgery: HR, 1.08, 95 percent CI, 1.03–1.13) for each 4-week delay. Varied estimates were seen for systemic treatment (HR range, 1.01–1.28). For radiotherapy, estimates were made for radical radiotherapy for head and neck cancer (HR, 1.09, 95 percent CI, 1.05–1.14), adjuvant radiotherapy after breast conserving surgery (HR, 0.98, 95 percent CI, 0.88–1.09), and adjuvant radiotherapy for cervix cancer (HR, 1.23, 95 percent CI, 1.00–1.50).

These results did not change in a sensitivity analysis of studies that had been excluded due to lack of information on comorbidities or functional status.

“Delays of up to 8 weeks and 12 weeks further increase the risk of death,” the researchers said. “For example, an 8-week delay in breast cancer surgery would increase the risk of death by 17 percent and a 12-week delay would increase the risk by 26 percent.”

These numbers translate into substantial excess mortality on a population level. For instance, a 12-week surgical delay for patients with breast cancer for a year (eg, during COVID-19 lockdown and recovery) would lead to 1,400 excess death in the UK, 6,100 in the US, 700 in Canada, and 500 in Australia, assuming surgery is the first treatment in 83 percent, and mortality without delay is 12 percent. [JAMA Oncol2016;2:330-9; http://tinyurl.com/pwkua34; https://gco.iarc.fr/today]

“The study results are timely in light of the current COVID-19 pandemic. Internationally, some countries have released national guidance on prioritization of surgical treatments for cancer, which do not appear to be supported by the results of this study,” the researchers noted.

“For example, at the beginning of the pandemic the UK NHS created a short-term surgical prioritization algorithm. Several indications were considered safe to be delayed by 10–12 weeks with no predicted impact on outcome, including all colorectal surgery,” they added. [https://www.asgbi.org.uk/userfiles/file/covid19/c0239-specialty-guide-essential-cancer-surgery-coronavirus-v1-70420.pdf]

“Therefore, our results can help to directly inform policy,” the researchers said. “[W]e found that increasing the wait to surgery from 6 weeks to 12 weeks would increase the risk of death in this setting by 9 percent.”