Severe primary organ-related complications in patients with de novo metastatic cancer: implications for prophylactic local therapy.

Purpose: Patients with de novo metastatic cancer develop local organ-related complications leading to hospitalizations, procedures, and reduced quality of life. Prophylactic local therapy (e.g., radiotherapy) has been proposed to reduce morbidity, but the incidence and timing of severe primary organ-related events (SPOREs) remain poorly defined. We quantified the cumulative incidence and spectrum of SPOREs to inform trials of prophylactic local therapy. Methods: We conducted a retrospective cohort study of 358 patients with de novo metastatic prostate, bladder, and pancreatic cancers treated between 2010 and 2023. SPOREs were defined using clinically meaningful, organ-specific criteria, excluding events within 30 days of diagnosis. Death was treated as a competing event, and cumulative incidence functions were estimated with the Fine-Gray method. Results: A total of 104 prostate, 59 bladder, and 195 pancreatic cancer patients (adenocarcinoma Conclusion: SPOREs represent a substantial source of morbidity in de novo metastatic cancer. Across disease sites, risk and timing appear driven significantly by anatomic vulnerability of the primary tumor rather than metastatic virulence or prognosis. Despite differing biology, pancreatic adenocarcinoma and neuroendocrine tumors demonstrated high local morbidity. These findings suggest anatomic context may better identify patients most likely to benefit from prophylactic local therapy aimed at reducing morbidity.