Presentation, Management, and Outcomes of Urinary Bladder Paraganglioma: Results From a Multicenter Study

Abstract

Context: Urinary bladder paraganglioma (UBPGL) is rare.

Objective: We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL.

Methods: We conducted a multicenter study of consecutive patients with pathologically confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality.

Results: Patients (n=110 total; n=56 [51%] women) were diagnosed with UBPGL at a median age of 50 years (interquartile range [IQR], 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after the initial diagnosis. Development of metachronous metastases was associated with younger age (hazard ratio [HR] 0.97; 95% CI, 0.94-0.99), UBPGL size (HR 1.69; 95% CI, 1.31-2.17), and a higher degree of catecholamine excess (HR 5.48; 95% CI, 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR 20.80; 95% CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality.

Conclusions: Only a minority of patients were diagnosed before biopsy/surgery, reflecting need for better diagnostic strategies. All patients with UBPGL should have lifelong monitoring for development of recurrence and metastases.

Keywords: catecholamine; diagnosis; micturition; prognosis.

Figure 1.

Mode of discovery of urinary bladder paraganglioma. Other symptoms of catecholamine excess included dizziness, tremor, syncope, flushing, paleness, sweating, anxiety, nausea, vomiting, abdominal pain, diarrhea, constipation, hypotension, chest pain, back pain, tinnitus, and weight loss. Urinary symptoms referred to hematuria, micturition disturbances, pain on urination, and pelvic pain. Other or unknown mode of discovery included evaluation for a known genetic association, evaluation for mass effect symptoms, incidentally after resection of other pelvic tumors, evaluation for other abnormalities (abnormal creatine or estimated glomerular filtration rate), and unknown. Types of biopsy included fine needle aspiration and diagnostic transurethral resection. Abbreviations: UBPGL, urinary bladder paraganglioma.

Figure 2.

Outcomes of patients with urinary bladder paraganglioma. A. Factors associated with repeat bladder surgery. B. Factors associated with metachronous metastasis. C. Determinants of disease-specific survival. Abbreviations: Dx, diagnosis; HR, hazard ratio; PPGL, pheochromocytoma and paraganglioma; SDHB, Succinate dehydrogenase complex iron sulfur subunit B; TURBT, transurethral resection of bladder tumor; UBPGL urinary bladder paraganglioma; UNR, upper limit of normal reference range. Hazard ratios and P values were based on univariable Cox analysis. Tumor size was determined based on the largest diameter of the UBPGL on histopathology or imaging (in patients not treated by surgery). UBPGL was considered multinodular when multiple distinct bladder PGL lesions were present. In patients with multinodular UBPGL, tumor size was defined as the largest diameter among all the nodules.

Figure 3.

Prognosis of patients with urinary bladder paraganglioma. A. The overall survival of patients with UBPGL. B. The disease-specific survival of patients with synchronous metastasis (red) and with metachronous metastasis (blue). P value was estimated by Kaplan-Meier curve and was based on patients with synchronous metastasis and with metachronous metastasis.

Figure 4.

Incidence rate of urinary bladder paraganglioma in Denmark 1997-2016. Abbreviation: UBPGL, urinary bladder paraganglioma.

Figure 5.

Mode of discovery of urinary bladder paraganglioma in different study period. There were no significant differences in the mode of UBPGL discovery in 3 study periods. 9 (33%), 10 (40%), and 14 (24%) of UBPGL were discovered by workup for symptoms of catecholamine excess in ≤ 2001, 2002-2011, and 2012-2021, P = 0.323; 9 (33%), 6 (24%), and 17 (29%) of UBPGL were detected during workup for urinary symptoms, P = 0.761; 5 (19%), 6 (24%), and 20 (34%) of UBPGL were found incidentally on imaging, P = 0.276; 4 (15%), 3 (12%) and 7 (12%) of UBPGL were discovered by other mode or with unknown discovery mode, P = 0.933. The rate of catecholamine workup (16 [59%], 19 [76%] and 37 [64%] P = 0.418) were also not significantly different among these 3 study periods. Abbreviations: UBPGL, urinary bladder paraganglioma. P value was calculated based on multiple pairwise analysis.