Complexities of Contemporary Bladder Cancer Care

NYU Case of the Month, September 2019

Ca s e o f t h e Mo n t h Complexities of Contemporary Bladder Cancer Care NYU Case of the Month, September 2019 Richard S. Matulewicz, MD, MS Department of Urology and Department of Population Health, NYU School of Medicine, New York, NY [Rev Urol. 2019;21(4):172–174] © 2020 MedReviews®, LLC A 56-year-old woman presents with a 1-year history of irritative voiding symptoms and a recent episode of painless gross hematuria. In the past 6 months, she reports dysuria and urinary frequency refractory to several courses of antibiotics for presumed urinary tract infection (UTI). She denies flank pain, suprapubic pain, weight loss, or other constitutional symptoms. Her medical history is significant for pre-diabetes and endometriosis. She is postmenopausal and is up to date with all age-appropriate screening examinations. Surgically, she’s had a breast biopsy which revealed a benign fibroadenoma. She is a never smoker but previously worked with photograph development chemicals in a print shop. There is no family history of genitourinary, gynecologic, or colon cancers. In the office, the bimanual examination was notable for a palpable 2-cm mass in the anterior vaginal vault in the region of the bladder neck. Preoperative Laboratory Results BUN: 15 mg/dL Creatinine: 0.7 mg/dL Voided urine cytology: negative for high-grade urothelial carcinoma Management The patient was evaluated with a CT urogram that demonstrated a mass at the bladder neck and right lateral bladder wall (Figure 1). There were no renal masses, no evidence of upper tract filling defects, and no pelvic or retroperitoneal lymphadenopathy. She was subsequently taken to the operating room for a cystoscopy and examination under anesthesia. Cystoscopy confirmed a sessile mass within the proximal urethra and bladder neck, contiguous with the right lateral wall of the bladder (Figure 2). Figure 1. CT urogram demonstrating a mass at the bladder neck and right lateral bladder wall. 172 • Vol. 21 No. 4 • 2019 • Reviews in Urology Complexities of Bladder Cancer Care continent of urine. Therefore, she underwent an anterior pelvic exenteration including urethrectomy, extended pelvic lymph node dissection, continent cutaneous urinary diversion (modified Indiana Pouch) with a myocutaneous flap reconstruction of her pelvic floor and vagina. Comment Figure 2. Cystoscopy confirms a sessile mass within the proximal urethra and bladder neck, contiguous with the right lateral wall of the bladder. The mass was resected to visual completion and not palpable on bimanual examination after transurethral resection of a bladder tumor (TURBT). The remainder of the pelvic examination and cervix were normal. Histopathology was consistent with a poorly differentiated carcinoma with extensive muscularis propria invasion (pT2). Further immunohistochemical testing was negative for traditional urothelial tissue stains (GATA-3, thrombomodulin, and uroplakin) but positive for neuroendocrine markers with small-cell features (CAM5.2, CD56, and synaptophysin). Her staging evaluation was complete with a brain MRI, chest CT, and bone scan, which demonstrated no evidence of metastatic disease. She was referred to medical oncology and completed four cycles of cisplatin and etoposide systemic chemotherapy. Imaging during and following chemotherapy demonstrated no local progression or development of metastatic disease. She was counseled extensively on the options for local consolidative therapy in the setting of an aggressive, but localized, neuroendocrine bladder cancer. The patient wished to have surgery but also prioritized remaining sexually active and This case highlights several complexities of contemporary bladder cancer care. First is the difficult, but common clinical scenario where a younger woman is diagnosed with bladder cancer after a protracted course of treatment for persistent lower urinary tract symptoms presumed to be due to infection. Despite being nearly four times more common in men, women with bladder cancer present at a more advanced stage, do worse after radical cystectomy, and have a lower 5-year cancerspecific survival than men.1 Several environmental, anatomic, and hormonal hypotheses for these phenomena have been presented without convincing evidence, but delays in diagnosis may offer an explanation. It is well established that women with hematuria are less likely to be referred to urologists for evaluation.2,3 When they are referred, it is typically later in their clinical course relative to men,4 especially in the setting of urinary tract symptoms that could be related to UTI.5 A high index of suspicion for a non-benign etiology of persistent “UTI” symptoms in women is essential. This case also highlights several important points in the management of bladder cancers with variant histology, particularly neuroendocrine and small-cell carcinomas. These rare and highly aggressive tumors present with advanced disease far more often than traditional urothelial carcinomas, many with early distant metastases. A complete staging evaluation, including brain imaging, is indicated. Multidisciplinary co-management of these patients with an experienced medical oncologist is essential as upfront systemic therapy is a hallmark of treatment. Neoadjuvant chemotherapy has been shown to significantly extend survival compared to cystectomy alone.6 Consolidative local therapy with either cystectomy should be reserved for patients who are excellent surgical candidates with a durable response to systemic therapy. Local radiotherapy is an additional option for local control in patients unable or unwilling to undergo cystectomy. Small-cell carcinomas are traditionally transiently responsive to chemotherapy with frequent early and distant relapse. Survival is closely linked to stage at initial presentation with most survival estimates for patients presenting with advanced disease between 7 and 13 months.7 Finally, and most importantly, enhancing survivorship in patients with bladder cancer should remain a priority in counseling and treatment. The morbidity associated with an anterior exenteration for a young, active woman is significant. Extensive discussion about all treatment options, including bladder-sparing procedures and diversion choices, is important. Centers with experienced reconstructive urologists and plastic surgeons can also offer vaginal reconstruction to preserve sexual function in select patients. References 1. 2. Shariat SF, Sfakianos JP, Droller MJ, et al. The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int. 2010;105:300-308. Matulewicz RS, Demzik AL, DeLancey JO, et al. Disparities in the diagnostic evaluation of microhematuria and implications for the detection of urologic malignancy. Urol Oncol. 2019;37:300.e1-300.e7. Vol. 21 No. 4 • 2019 • Reviews in Urology • 173 Complexities of Bladder Cancer Care continued 3. 4. Ark JT, Alvarez JR, Koyama T, et al. Variation in the diagnostic evaluation among persons with hematuria: influence of gender, race and risk factors for bladder cancer. J Urol. 2017;198:1033-1038. Johnson EK, Daignault S, Zhang Y, Lee CT. Patterns of hematuria referral to urologists: does a gender disparity exist? Urology. 2008;72:498-502; discussion 502-503. 5. 6. Richards KA, Ham S, Cohn JA, Steinberg GD. Urinary tract infection-like symptom is associated with worse bladder cancer outcomes in the Medicare population: implications for sex disparities. Int J Urol. 2016;23:42-47. Lynch SP, Shen Y, Kamat A, et al. Neoadjuvant chemotherapy in small cell urothelial cancer improves pathologic downstaging and long-term outcomes: 174 • Vol. 21 No. 4 • 2019 • Reviews in Urology 7. results from a retrospective study at the MD Anderson Cancer Center. Eur Urol. 2013;64:307-313. Ismaili N, Heudel PE, Elkarak F, et al. Outcome of recurrent and metastatic small cell carcinoma of the bladder. BMC Urol. 2009;9:4.