The presenting symptoms of patients with appendiceal malignant tumors.

824 Background: Timely detection of appendiceal malignant tumors is a clinical priority because of the propensity for this malignancy to metastasize to the peritoneal cavity. Up to one in every 2 patients with this rare tumor type will present with distant metastatic disease, owing to there being no standardized screening tests for early detection of primary appendiceal cancers. Case reports have pointed to broad/non-specific symptoms of patients diagnosed with appendiceal malignant tumors, yet information is needed from large cohorts to support prompt/accurate clinical diagnoses. Methods: We analyzed data from patients with a pathologically-confirmed first primary appendiceal malignant tumor (AC) who prospectively enrolled in the nation-wide Genetics of Appendix Cancer [GAP] clinical cohort study (Clinicaltrials.gov, NCT05734430) between November 2022 and May 2024. The primary outcome was presenting symptoms that led to AC diagnosis. Symptom effects and interactions with diagnosis age/year, sex, body mass index (BMI), and tumor histology, were quantified with negative binomial regression models and presented as incidence rate ratios (IRRs) and 95% confidence intervals. Results: Of the 352 patients included in our analyses (median [IQR] age, 51.0 [42-59] yr), 77.6% were female and 96.6% had an adenocarcinoma histology. Seventy-seven percent of patients (n=270) reported one or more presenting symptoms, of whom 55.2% (n=149) experienced these symptoms for 3+ months prior to diagnosis. On average, patients reported 3 symptoms (mean: 2.9, SD 3.0). The most prevalent symptoms among males and females were abdominal pain (57.1%), bloating/distension (32.1%), pelvic pain (18.5%), and abdominal/pelvic mass (18.2%). Overall, patients with early-onset AC [age<50] more commonly presented with symptoms versus cases with late-onset AC (82.9% vs 71.7%, p =0.01). This finding persisted in adjusted models—the number of symptoms was highest among younger patients, rapidly decreased and plateaued around age 50 (IRR 0.97, 95%CI 0.95-0.99, p =0.002), and slowly increased again with older age (IRR 1.03, 95%CI 1.00-1.05, p =0.037). Patient sex was also significantly associated with symptom number, as males had a lower rate of symptoms versus females (IRR 0.63, 95%CI 0.48-0.83, p =0.001). In contrast, histology (IRR 1.03, 95%CI 0.53-2.02), diagnosis year (IRR 1.01, 95%CI 0.99-1.04, p =0.35) and BMI (IRR 1.01, 95%CI 0.99-1.02) were not associated with symptom number in adjusted models. Conclusions: In a large nation-wide cohort, three of every 4 patients were symptomatic prior to primary AC diagnosis. Compared to the rapid time course of acute appendicitis, over 40% of this population presented with symptoms for 3+ months prior to AC diagnosis. The higher symptom burden among young patients and females supports the need for clinical providers to keep occult appendiceal tumors in the differential diagnosis of patients presenting in this manner.