Can Low-Dose Aspirin Reduce Colorectal Cancer Recurrence?

The benefits of low-dose aspirin have been debated for years, particularly regarding its role in reducing coronary disease. However, its potential in preventing and managing colorectal cancer (CRC) has gained significant attention. A recent study found that low-dose aspirin reduced CRC recurrence by over 50% in patients whose tumors harbored mutations in the PI3K signaling pathway. These findings underscore the critical importance of upfront genomic testing for CRC patients. 

This is the first trial to demonstrate that PI3K pathway mutations predict aspirin response, significantly expanding the targetable patient population—given that approximately 30% of CRCs carry these mutations. While aspirin’s potential as a chemopreventive agent for CRC has been explored, definitive data confirming its effectiveness and its adoption in clinical practice have been lacking until now. 

The study included 626 patients (median age: 66 years; 52% women) with stage II–III colon cancer (67%) or stage I–III rectal cancer (33%) across 33 hospitals in Sweden, Denmark, Finland, and Norway. Patients were stratified based on specific PI3K pathway alterations and randomly assigned to receive either aspirin (160 mg daily) or a placebo for three years. 

The primary outcome was CRC recurrence, with disease-free survival as a secondary endpoint. In patients with PIK3CA mutations, aspirin reduced the risk of recurrence by 51%, with a three-year recurrence rate of 7.7% in the aspirin group compared to 14.1% in the placebo group. The benefit of aspirin was consistent across all subgroups, including men and women, those with colon or rectal cancer, patients who received neoadjuvant or adjuvant treatment, and those with stage I, II, or III disease. 

This study reinforces the need to integrate genomic marker data into clinical registries to guide personalized treatment strategies that can effectively reduce cancer recurrence. 

Predicting Cancer Recurrence

One of the most frequent questions from patients is whether their cancer will come back after their surgical, radiation, or chemotherapy treatment is complete. Analyses of circulating tumor cells or the DNA associated with those cells (ctDNA) may be the answers. Can postoperative circulating tumor DNA (ctDNA) status predict recurrence-free survival (RFS) in patients with esophagogastric cancer with a pathologic complete response (pCR) or near-pCR?

A recent study evaluated this concept in a group of patients with esophagogastric cancer (EGC). Of the 60% of patients diagnosed with potentially curative locoregional disease in the United States, only 25%-30% survive five years from the time of diagnosis. After neoadjuvant therapy (NAT) and surgery, up to one third of patients with esophagogastric adenocarcinoma with a pathologic complete response (pCR; tumor regression grade 0 [TRG-0]) will recur.

The study aims to evaluate postoperative ctDNA as a predictor of recurrence in patients with pCR or near-pCR after curative-intent neoadjuvant chemotherapy or neoadjuvant chemoradiation and surgery. Within the subgroup of patients with EGC and favorable pathologic responses (TRG 0-1) after NAT, the presence of postoperative ctDNA identified patients with elevated recurrence risk. ctDNA is prognostic for recurrence even in patients who achieved a pCR or near-pCR.

With prospective validation in a larger cohort, ctDNA testing may become a useful surrogate modality along with other clinicopathologic factors to help identify patients who would benefit from adjuvant treatment. Capture of ctDNA results in our cancer registries will, no doubt, be important for patients with a variety of malignancies.

The Disruption and Recovery of Cancer Diagnoses Following COVID-19

As we begin 2025, discussions of flu-like illnesses are extremely relevant, especially ongoing issues related to the COVID-19 pandemic. A critical question to consider is: to what extent was cancer detection in the U.S. disrupted during the pandemic's first year, and how much progress was made toward recovery in the second year?

A recent study examining nearly 16 million patients diagnosed with invasive cancer between 2000 and 2021 revealed the estimated cancer incidence was 9% below projections in 2020. However, by 2021, actual incidence rates aligned with projections. These findings highlight the need for continued recovery in cancer detection efforts to address cases that went undiagnosed during the pandemic.

The COVID-19 pandemic disrupted the timely diagnosis of cancer, which remained the second leading cause of death in the U.S. throughout this period. The study involved an epidemiologic analysis of nationally representative, population-based cancer incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program. The analysis included patients diagnosed with cancer between January 1, 2000, and December 31, 2021. Conducted in May 2024, the study utilized the April 2024 SEER data release, which provides incidence data up to December 31, 2021.

Differences between the expected and observed cancer incidence in 2020 were compared with 2021, with additional analyses by demographic subgroups (sex, race and ethnicity, and age group) and community (county-level) characteristics. A key strength of this study was the use of data from SEER, representing almost 50% of the US population. Additionally, the approach is easily reproducible, facilitating the continued monitoring of these epidemiologic trends.

The analysis could have been strengthened by utilizing a unified, high-quality national cancer registry encompassing 100% of the U.S. population. However, such a registry does not currently exist. The most comprehensive resource available is the National Cancer Data Base (NCDB), which covers approximately 70% of U.S. cancer cases. This limitation likely affected the estimates of cancer cases and deficits in diagnoses, as the figures were extrapolated to the national level using data from the SEER program. While the resulting estimates aligned reasonably well with other widely cited sources, including the American Cancer Society and the CDC's U.S. Cancer Statistics, they were modestly lower—by about 6%—than these alternative benchmarks.

This cross-sectional study of nationally representative cancer registry data from the SEER Program found a meaningful recovery in cancer detection rates in 2021 following significant disruptions in 2020. However, an estimated 127,931 patients nationwide remained undiagnosed in 2021, potentially leading to profound and long-lasting consequences. These findings underscore the urgent need to reestablish timely care for patients with undiagnosed cancer during the pandemic to mitigate worsening disparities in cancer outcomes and to reduce future cancer-related morbidity and mortality.