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One of the most pressing questions during the coronavirus pandemic has been its impact on cancer detection, diagnosis, and treatment. During the first Covid-19 surge, swamped health-care systems suspended cancer screenings and some in-person care while some people stayed away for fear of Covid-19 infection.

Screening rates fell precipitously for cancers with common tests, including mammograms for breast cancer, Pap tests for cervical cancer, PSA testing for prostate, CT scans for lung cancer and colonoscopies for colorectal cancer. Those rates have rebounded somewhat, but another question may take longer to answer: Does the delay in screening matter?

A small new study from France is one of the first to show how diagnostic delays could lead to worse outcomes. The paper, published Wednesday in JAMA Network Open, compared people newly diagnosed with metastatic colorectal cancer before and after the country’s 55-day pandemic lockdown in 2020. It found that 40 people diagnosed with metastatic colorectal cancer after the lockdown had a tumor burden nearly seven times higher than 40 people diagnosed before the pandemic. For people with a higher tumor burden, their median survival decreased from 20 months to just under 15 months.

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The researchers didn’t set out to study the pandemic’s impact on cancer. They were working on a large clinical trial using blood tests that measure circulating DNA to see if patients with metastatic colorectal cancer had certain genetic mutations that might respond to a targeted therapy. These patients had originally gone to oncologists at one of 18 hospitals after cancer was detected on screening tests or after they asked their doctors about troubling symptoms. Following positive colonoscopy and then positive detection of metastatic tumors with imaging techniques, the patients had their blood drawn to find RAS and BRAF mutations, using circulating DNA analysis for the PANIRINOX study.

The researchers, led by Alain Thierry, director of research at INSERM and Institut de Recherche en Cancérologie de Montpellier, noticed significantly higher levels of circulating tumor DNA in most of the patients diagnosed after screening resumed on May 11, 2020, compared to 228 patients diagnosed before lockdown began on March 9, 2020. In their previous work, circulating DNA analysis had shown strong prognostic value.

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“The use of a clinically validated blood test enabled us to present the first quantitative assessment of tumor burden related to a specific cancer during pre- and post-lockdown periods,” Thierry told STAT. “These numbers highlight the lockdown’s human cost, since our data suggested median survival decreased by half.”

Other pandemic-inspired studies based on modeling have painted a grim picture of the toll missed cancer screening tests might take over time. In June 2020, a National Cancer Institute model looking just at breast cancer and colorectal cancer predicted there would be 10,000 excess deaths in the U.S. over the next 10 years because of pandemic-related delays in diagnosing and treating these tumors. And that assumed cancer care would rebound in six months.

That same month, a study conducted at the Mass General Brigham hospital system looked at what happened when screening picked up again. The researchers found that Pap tests, PSA tests, mammograms, colonoscopies, and CT scans for lung cancer all dropped significantly from March through June 2020. But when screening resumed, the number of potential “missed” diagnoses was lower than expected, likely because the percentage of cancer and precancer diagnoses during that peak pandemic period was higher. That probably means patients who still got tested within that window were somehow at higher risk.

More recent data from Quest Diagnostics showed that screening has yet to return to pre-pandemic levels. An August analysis from the clinical laboratory said in eight cancers — breast, colorectal, lung, pancreatic, cervical, gastric, esophageal, or prostate — diagnoses returned to pre-pandemic levels in the summer of 2020, but dropped below pre-pandemic numbers again from November through March of 2021.

In the new study from France, there are some caveats. Its authors say the exploratory study is a snapshot of an evolving situation, and experts not involved in the study also say more research — and time — will be needed before drawing larger conclusions.

Toni Choueiri, a medical oncologist at Dana-Farber Cancer Institute and a co-author of the Mass General Brigham study, told STAT its focus on patients with metastatic disease makes it harder to apply those results to the wider population of people being screened for colorectal cancer.

Thierry noted that about 22% of colorectal cancer cases are diagnosed at the metastatic stage, totaling roughly 400,000 patients each year worldwide including about 30,000 in the U.S.

Quoc-Dien Trinh of Dana-Farber and Brigham and Women’s Hospital told STAT that despite the relatively small groups of patients who underwent screening before and after the first lockdown in the French study, “we can all agree that the consequences of the Covid-19 pandemic on cancer care are real. It will take years to fully understand the pandemic’s impact, but it would not be entirely surprising to find that we are nowadays treating a higher proportion of individuals presenting with late-stage cancers … with downstream effects on cancer mortality.”

Thierry said colorectal cancer should be a major target for any intervention to minimize Covid-related diagnostic delays.

“Our data points first, to the crucial importance of early detection; second, to [the need] to maintain screening programs and diagnostic services during a pandemic; and third, to the need … to minimize patient’s fears by ensuring [better] communication,” he said.

Correction: An earlier version misstated the name of the journal where the study was published.

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