In a population-based study reported in a research letter in JAMA Oncology, Bateni et al found that 8% of patients with neuroendocrine tumors (NETs) developed second primary cancers over approximately 7.5 years of follow-up, with types of secondary malignancies differing according to NET type.
The study used Surveillance, Epidemiology, and End Results registry data on patients aged ≥ 20 years with gastrointestinal, pancreatic, or lung primary invasive NETs diagnosed between 2000 and 2016.
Key Findings
Among a total of 58,596 patients with NETs, 4,612 (7.9%) had second primary cancers. Median follow-up was 89 months (interquartile range [IQR] = 49–133 months) among patients with second primary cancers and 44 months (IQR = 15–93 months) for those without second primary cancers. NET histology was identified in 16.2% of the second primary cancers.
Median time to second primary cancers was 40 months (IQR = 17–77 months). The 5-year cumulative incidence of second primary cancers was 5.4% (95% confidence interval [CI] = 5.2%–5.6%) among all patients with second primary cancers, 5.9% (95% CI = 5.6%–6.2%) among those with gastrointestinal NETs, 3.8% (95% CI = 3.3%–4.4%) among those with pancreatic NETs, and 4.8% (95% CI = 4.4%–5.2%) among those with lung NETs.
Overall, compared with risk for all cancers in the general population, risk of second primary cancers in patients with NETs was increased by 35% (standardized incidence ratio [SIR] = 1.35, 95% CI = 1.31–1.39).
In this population-based analysis, there was an increased risk of second primary cancers after NET diagnosis.... These data highlight the need to consider detection strategies for second primary cancers [and] NET surveillance tailored to NET-specific and patient factors. Further investigations are warranted regarding specific surveillance regimens and prognostic implications.— Bateni et al
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Patients with gastric NETs had an increased risk of esophageal (SIR = 2.81, 95% CI = 1.13–5.80), small intestine (SIR = 9.85, 95% CI = 5.25–16.85), pancreatic (SIR = 2.59, 95% CI = 1.60–3.95), and liver second primary cancers (SIR = 2.76, 95% CI = 1.38–4.93).
Patients with appendiceal NETs had an increased risk of small intestine (SIR = 20.74, 95% CI = 11.04–35.46), colorectal (SIR = 3.04, 95% CI = 2.09–4.27), and lung second primary cancers (SIR =1.62, 95% CI = 1.05–2.40).
Patients with colon NETs had an increased risk of small intestine second primary cancers (SIR = 7.76, 95% CI = 3.72–14.28), and those with rectal NETs had an increased risk of pancreatic (SIR = 1.45, 95% CI = 1.02–1.99), lung (SIR = 1.20, 95% CI = 1.02–1.41), and prostate second primary cancers (SIR = 1.43, 95% CI = 1.25–1.63).
Patients with small intestine NETs had an increased risk of liver (SIR = 1.59, 95% CI = 1.02–2.37) and prostate (SIR = 1.35, 95% CI = 1.17–1.55) but not colorectal second primary cancers (SIR = 0.80, 95% CI = 0.62–1.01).
Patients with pancreatic NETs had an increased risk of gastric (SIR = 2.49, 95% CI = 1.24–4.46) and small intestine second primary cancers (SIR = 8.79, 95% CI = 4.54–15.36).
An increased risk of second primary cancers was observed for every 10-year age group vs 20 to 29 years (subdistribution hazard ratios [SHRs] = 1.82–5.71, all P < .01) and for Black vs White patients (SHR = 1.10, P = .02). Reduced risk was observed for female vs male patients (SHR = 0.81, P < .01); poorly differentiated (SHR = 0.69, P < .01) and undifferentiated (SHR = 0.45, P < .01) vs well-differentiated NET grade; and regional (SHR = 0.83, P < .01) and distant (SHR = 0.39, P < .01) vs local NET stage.
Compared with patients with colorectal NETs, those with gastric (SHR = 1.52, P < .01) and small intestine NETs (SHR = 1.15, P < .01) had a higher risk of second primary cancers, and those with pancreas NETs had a lower risk (SHR = 0.82, P <.01).
The authors concluded, “In this population-based analysis, there was an increased risk of second primary cancers after NET diagnosis. At 5 years, for every 100 patients with NETs, 5 were diagnosed with a second primary cancer, representing 35% more cases than expected in the general population. The patterns observed were distinct from those expected from known NET-related genetic syndromes…. These data highlight the need to consider detection strategies for second primary cancers [and] NET surveillance tailored to NET-specific and patient factors. Further investigations are warranted regarding specific surveillance regimens and prognostic implications.”
Julie Hallet, MD, of Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, is the corresponding author for the JAMA Oncology article.
