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Nomogram for predicting hepatocellular carcinoma specific survival in patients with and without second primary malignancies based on competing risk analysis
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DOI：10.1007/s12672-026-05687-6.png)
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Abstract
En 中文
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related mortality worldwide. Patients with HCC may develop second primary malignancies (SPMs), While the impact of second primary malignancies (SPMs) on overall survival in HCC patients has been examined in previous population-based studies, competing risk analyses of HCC-specific mortality—formally treating non-HCC death as a competing event rather than censoring it—remain scarce. The present study aimed to apply the Fine-Gray subdistribution hazard model to identify independent prognostic factors for HCC-specific survival in patients with and without SPMs, and to develop and validate a clinically applicable nomogram for individualized risk prediction. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with HCC between 2004 and 2020. A total of 12,867 patients were included: 9,479 without SPM and 3,388 with SPM. Competing risk analysis using the Fine-Gray subdistribution hazard model was performed to identify independent prognostic factors for HCC-specific survival, with non-HCC death treated as a competing event. A nomogram was constructed based on multivariable analysis results, and its predictive performance was evaluated using calibration curves and decision curve analysis (DCA). The Fine-Gray analysis showed that the presence of SPM was independently associated with a lower risk of HCC-specific mortality (subdistribution hazard ratio [SHR], 0.691; 95% confidence interval [CI], 0.638–0.748; P < 0.001). Other independent prognostic factors included age (SHR, 1.010; 95% CI, 1.005–1.015; P < 0.001), male sex (SHR, 1.121; 95% CI, 1.014–1.239; P = 0.025), Asian or Pacific Islander race (SHR, 0.791; 95% CI, 0.706–0.887; P < 0.001), tumor size (SHR, 1.001; 95% CI, 1.001–1.001; P < 0.001), macrovascular invasion (SHR, 1.637; 95% CI, 1.344–1.993; P < 0.001), hepatectomy (SHR, 0.337; 95% CI, 0.295–0.384; P < 0.001), radiotherapy (SHR, 1.394; 95% CI, 1.141–1.705; P = 0.001) and chemotherapy (SHR, 1.432; 95% CI, 1.276–1.608; P < 0.001). The nomogram demonstrated acceptable calibration for predicting 1-, 3- and 5-year HCC-specific survival probabilities, and DCA indicated its clinical utility across a range of threshold probabilities. The presence of SPM was associated with improved HCC-specific survival, possibly reflecting more intensive surveillance and earlier detection in this patient subset. The nomogram developed here may serve as a practical tool (https://superb-raindrop-eb8013.netlify.app/) for individualized prognostic assessment and treatment decision-making in clinical practice.
Keywords:
Hepatocellular carcinoma
Second primary malignancy
Competing risk analysis
Nomogram
SEER database
Prognosis
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