2140 - Severe Primary Organ-Related Complications in Patients with De Novo Metastatic Cancer: Implications for Prophylactic Local Therapy

Purpose/Objective(s):

Patients presenting with de novo metastatic cancer frequently experience local organ-related complications leading to hospitalizations, urgent procedures, and reduced quality of life. Prophylactic local therapy (i.e. radiotherapy) to the primary tumor has been proposed to diminish morbidity, even without a survival benefit; however, the incidence and timing of severe primary organ-related events (SPOREs) in metastatic disease remain poorly defined. We quantified the cumulative incidence and spectrum of SPOREs across multiple cancer types to inform trials evaluating prophylactic local therapy.

Materials/Methods:

We conducted a retrospective cohort study of 358 patients with de novo metastatic prostate, bladder, and pancreatic cancers treated at a tertiary academic center between 2010 and 2023. SPOREs were defined using clinically meaningful, organ-specific criteria capturing obstructive, bleeding, infectious, and pain-related complications attributable to the intact primary tumor. Events occurring within 30 days of diagnosis were excluded. Death was treated as a competing event, and cumulative incidence functions were estimated using the Fine-Gray method.

Results:

At least one SPORE occurred in 11% of prostate, 25% of bladder, 39% of pancreatic adenocarcinoma, and 59% of pancreatic neuroendocrine tumor patients. At 24 months, cumulative incidence of SPOREs was 3.3% (prostate), 27.2% (bladder), 40.0% (pancreatic adenocarcinoma), and 45.5% (pancreatic neuroendocrine tumors), with significant differences across cancer types (p<0.001). Incidence plateaued after 24 months for bladder and pancreatic adenocarcinoma, whereas prostate cancer and pancreatic neuroendocrine tumors demonstrated continued risk through 60 months. The most common events were urinary obstruction in prostate and bladder cancer and biliary obstruction/cholangitis in pancreatic cancer.

Conclusion:

SPOREs represent a substantial and clinically meaningful source of morbidity in patients with de novo metastatic cancer. Across disease sites, the risk and timing of these events appear driven primarily by anatomic vulnerability of the primary tumor (susceptibility to obstruction, mass effect, and organ compromise), rather than metastatic virulence or prognosis. Notably, cancers with markedly different biological behavior, such as pancreatic adenocarcinoma and pancreatic neuroendocrine tumors, demonstrated similarly high burdens of local morbidity. Our estimates show external validation in two ways: (1) the observed prostate SPORE burden is consistent with serious genitourinary event rates reported in PEACE-1 among patients managed without prostate radiotherapy, and (2) the incidence of pancreatic SPOREs closely mirrors hospitalization rates from local complications reported in prior population-based studies. These findings suggest anatomic context may better identify cancers most likely to benefit from prophylactic local therapy aimed at reducing morbidity.