Second Primary Malignancies in Gastrointestinal Cancer Survivors: Epidemiology, Risk Factors, and Future Prediction Models
- 1, Scranton, PA 18505, USA; (J.Y.); (T.B.)
- 2Borland Groover, Baptist Medical Center-Downtown, Jacksonville, FL 32207, USA
Abstract
Advances in gastrointestinal (GI) cancer care have produced a growing population of long-term survivors at risk of second primary malignancies (SPMs). SPM definitions vary across studies, and SPMs remain underrepresented in cancer forecasting and prediction tools for GI cancer survivors. We conducted a narrative review across major GI cancer subtypes, summarizing site-specific SPM risk, key etiological pathways, and available prediction tools. Approximately one in ten colorectal cancer (CRC) survivors develops an SPM at ten years (pooled SIR ~1.15), a figure specific to CRC that does not generalize to other GI sites. Gastric cancer survivors carry excess risk of thyroid (O/E 2.00), esophageal, small intestinal, and pancreatic (O/E 1.60) malignancy, amplified by radiotherapy. Esophageal squamous cell carcinoma survivors show markedly elevated risk of upper aerodigestive tract tumors, consistent with field cancerization. Lynch syndrome (~16% second CRC risk at 10 years) and familial adenomatous polyposis (near-100% lifetime CRC risk without colectomy) confer some of the highest lifetime risks of metachronous GI malignancy reported to date. Most forecasting frameworks treat cancer incidence as a single event and do not adequately capture survivor-specific transitions, competing mortality, or germline susceptibility. GI cancer survivors form a distinct group whose risk is often overlooked. Harmonizing SPM definitions, extending multistate and competing-risk modeling, and integrating hereditary-risk stratification are near-term priorities for individualized surveillance.
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BibTeX
@article{yadav2026second,
title = {{Second Primary Malignancies in Gastrointestinal Cancer Survivors: Epidemiology, Risk Factors, and Future Prediction Models}},
author = {Jyoti Yadav and Thomas Balizzakiwa and Hemant Goyal},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193195},
url = {https://europepmc.org/article/PMC/PMC13664306},
note = {CC BY},
}
RIS
TY - JOUR
TI - Second Primary Malignancies in Gastrointestinal Cancer Survivors: Epidemiology, Risk Factors, and Future Prediction Models
AU - Jyoti Yadav
AU - Thomas Balizzakiwa
AU - Hemant Goyal
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18193195
UR - https://europepmc.org/article/PMC/PMC13664306
AB - Advances in gastrointestinal (GI) cancer care have produced a growing population of long-term survivors at risk of second primary malignancies (SPMs). SPM definitions vary across studies, and SPMs remain underrepresented in cancer forecasting and prediction tools for GI cancer survivors. We conducted a narrative review across major GI cancer subtypes, summarizing site-specific SPM risk, key etiological pathways, and available prediction tools. Approximately one in ten colorectal cancer (CRC) survivors develops an SPM at ten years (pooled SIR ~1.15), a figure specific to CRC that does not generalize to other GI sites. Gastric cancer survivors carry excess risk of thyroid (O/E 2.00), esophageal, small intestinal, and pancreatic (O/E 1.60) malignancy, amplified by radiotherapy. Esophageal squamous cell carcinoma survivors show markedly elevated risk of upper aerodigestive tract tumors, consistent with field cancerization. Lynch syndrome (~16% second CRC risk at 10 years) and familial adenomatous polyposis (near-100% lifetime CRC risk without colectomy) confer some of the highest lifetime risks of metachronous GI malignancy reported to date. Most forecasting frameworks treat cancer incidence as a single event and do not adequately capture survivor-specific transitions, competing mortality, or germline susceptibility. GI cancer survivors form a distinct group whose risk is often overlooked. Harmonizing SPM definitions, extending multistate and competing-risk modeling, and integrating hereditary-risk stratification are near-term priorities for individualized surveillance.
SN - 2072-6694
ER -