PROSTATE cancer (PCa) is the most frequently diagnosed cancer in men and the second leading cause of cancer-related deaths worldwide. Advances in early detection and treatment have significantly improved survival rates, but this longer survival also increases the risk of developing a second primary malignancy (SPM). Unlike recurrence or metastasis, SPMs represent new cancers that occur independently of the first tumour. Previous research has shown that up to 22% of all SPMs may occur in men with prostate cancer, underlining the clinical importance of accurate risk assessment.
A recent study has developed and validated a new prognostic nomogram to predict survival in PCa patients diagnosed with SPMs. Drawing on data from the SEER database, the researchers identified 57 different types of SPM, with the bladder, lungs, bronchi and cutaneous melanoma emerging as the most common sites. Notably, bladder cancer appeared particularly prevalent among this patient group, highlighting the central role of urinary tract malignancies in PCa-related SPMs.
The nomogram integrates seven key clinical and demographic factors, including age, marital status, SPM site, AJCC stage, metastasis status, prostate-specific antigen (PSA) levels, and history of PCa surgery. Compared with the conventional AJCC staging system, the model demonstrated superior predictive accuracy, confirmed by net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). This enhanced performance suggests that the nomogram provides a more refined, personalised tool for clinicians when assessing survival prospects and guiding treatment decisions.
In addition to the prognostic model, the study employed two-sample Mendelian randomisation (TSMR) to explore genetic links between PCa and its ten most common associated SPMs. The analysis revealed a novel causal association between PCa and urothelial cancers (including bladder and upper tract tumours), suggesting shared pathogenic mechanisms such as chronic inflammation and genetic mutations. No significant causal connections were found with other malignancies, indicating that environmental factors may play a larger role in their development.
Overall, this research offers a practical web-based prediction tool that can support clinicians in tailoring patient follow-up and treatment. By combining epidemiological evidence with genetic insights, the study provides valuable advances in understanding and managing SPMs among prostate cancer survivors
Reference
Zhang Q et al. Development of a prognostic nomogram and genetic insights for prostate cancer patients with secondary primary malignancies: a SEER retrospective cohort study and Mendelian randomization analysis. UroPrecision. 2025;DOI:10.1002/uro2.70017.
