Risk of second primary cancer after treatment for esophageal cancer: A pooled analysis of nine cancer registries

Gansu Provincial Academy of Medical Sciences, Gansu Provincial Cancer Hospital, Lanzhou, China.
Diseases of the Esophagus (Impact Factor: 1.78). 11/2011; 25(6):505-11. DOI: 10.1111/j.1442-2050.2011.01273.x
Source: PubMed


The introduction of new treatments for esophageal cancer including surgery, chemotherapy, radiotherapy, or a combination of these modalities has not only improved patient survival, but may also increase the risk of the second primary cancers. The available evidence is conflicting with most risk estimates based on sparse numbers. Here we estimated standardized incidence ratios (SIRs) of second cancer among 24,557 esophageal cancer survivors (at least 2 months) in the Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2007, who had been followed up for median 6.5 years (range 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.34, 95% confidence interval [CI]= 1.25-1.42) among the survivors compared with the general population; the SIRs for cancers of oral and pharynx, stomach, small intestine, larynx, lung and bronchus, thyroid and prostate cancer were 8.64 (95% CI = 7.36-10.07), 2.87 (95% CI = 2.10-3.82), 3.80 (95% CI = 1.82-7.00), 3.19 (95% CI = 2.12-4.61), 1.68 (95% CI = 1.46-1.93), 2.50 (95% CI = 1.25-4.47), and 0.77 (95% CI = 0.65-0.90), respectively. Radiotherapy raised cancer risk of larynx (SIR = 3.98, 95% CI = 2.43-6.14) and thyroid (SIR = 3.57, 95% CI = 1.54-7.03) among all esophageal cancer survivors. For patients who had 5-9 years of follow up after radiotherapy, the SIR for lung cancer was 3.46 (95% CI = 2.41-4.82). Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx, larynx, lung, and thyroid, while at a decreased risk for prostate cancer. These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx, lung, and thyroid. Thus, randomized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted.

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    ABSTRACT: Background: Development of a second primary malignancy (SPM) after an index esophageal cancer is fairly rare, primarily due to decreased survival in patients with esophageal cancer. However, with advances in early detection and therapy, the number of long-term survivors is increasing, as is the incidence of SPMs in this population. Scope: We review herein the published literature on the incidence of SPMs after an index esophageal cancer as well as its associated risk factors, prognosis and surveillance. We discuss predisposing factors that may contribute to the development of SPMs, epidemiology and attempts at chemoprevention. Findings: Data from population-based studies, retrospective reviews and case reports indicate an increased risk of SPMs in patients with esophageal cancer with reported incidence rates between 8.3 and 27.1%. Index esophageal squamous cell carcinomas have a higher association with other tobacco-related cancers such as those of the head and neck and lung. They have also shown an association with second primary cancers of the breast, stomach, thyroid, and kidney. Individuals with esophageal adenocarcinomas are at a higher risk of developing second cancers of the stomach, oropharynx and lung/bronchus. Other primary cancer sites involved include the kidney, colorectum and pancreas. Common risk factors including lifestyle and genetic alterations may explain the increased incidence of second primary cancers in this patient population. Conclusions: Risk of developing a second malignancy should be anticipated after curative treatment of esophageal cancer, and raises concerns for optimal surveillance and therapy of these patients. Recent literature suggests similar survival rates in esophageal cancer patients with and without SPMs. With the increasing incidence of SPMs in subjects with esophageal cancer, there may be benefit to close screening for and aggressive therapy of SPMs. However, further studies are needed to elucidate optimal management strategies.
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