73-Year-Old Man With Locally Advanced Urothelial Carcinoma

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Neeraj Agarwal, MD: I’m going to talk about a 73-year-old man with locally advanced urothelial carcinoma of the bladder. This is a 73-year-old man who presents with lower urinary tract symptoms with intermittent hematuria. His past medical history is actually unremarkable—hypertension that is well controlled on angiotensin receptor blockers, mild hepatic and renal impairment. There is really nothing remarkable. Otherwise, the patient complains of past symptoms of intermittent hematuria and occasional difficulty in passing urine.

Upon examination, his initial clinical work-up was pretty unremarkable. Laboratory data showed mild anemia, with a hemoglobin of 11.4 g/dL; white blood cells, 3.5 x 109 cells/L; AST [aspartate aminotransferase] and ALT [alanine aminotransferase] liver enzymes are 3 to 4 times elevated; normal bilirubin; creatinine clearance of 35 mL/min; and the patient has a history of renal impairment. So there’s nothing really surprising here.

A cystoscopy showed a 2.6-cm mass around the neck of the bladder. A transurethral resection of the bladder tumor was performed and showed that the tumor was invading the perivesical tissue. This was a urothelial carcinoma.

The CT scan of the abdomen, pelvis, and chest shows a large bladder mass and evidence of multiple regional lymph nodes involving perivesical and sacral lymph nodes. Locally advanced bladder cancer was negative for distant metastases—nothing was shown on the scans in the liver, lung, bones, etc. It was determined that the patient was unresectable. He was not a candidate for definitive surgery or radiation therapy. The final staging for this patient is stage IIIB, and he has an ECOG performance status 1.

The question is, how do we treat the patient? Just to summarize, this is a 73-year-old, otherwise healthy person. He has mild renal impairment with a slight elevation of liver enzymes; his etiology is unclear. He comes in with hematuria, mild obstructive urinary symptoms, and a cystoscopy shows a bladder mass. This is muscle invasive urothelial carcinoma invading into the perivesical tissue. This patient is not considered a candidate for definitive radiation therapy or surgery. What are the next steps for this patient?

Upon diagnosis of stage IIIB locally advanced unresectable urothelial carcinoma of the bladder, this 73-year-old is otherwise pretty healthy. He has an ECOG performance status of 1. He was started on chemotherapy, with gemcitabine and carboplatin. Carboplatin was selected because his creatinine clearance was 35 mL/min. This patient was not deemed to be a candidate for cisplatin chemotherapy.

After 6 cycles of carboplatin-gemcitabine therapy, the patient had stable disease on scans. There was no evidence of disease progression. A CT scan shows a slight decrease in the bladder mass and improvement in the size of the lymph nodes, really qualifying for stable disease as the best response. During this time, the data from the JAVELIN Bladder 100 trial were presented at ASCO [American Society of Clinical Oncology Annual Meeting] 2020, showing that frontline maintenance avelumab in this setting was associated with improved survival. Based on these data, the patient was started on frontline avelumab maintenance therapy at 3 to 4 weeks after completion of chemotherapy with gemcitabine-carboplatin.

Transcript edited for clarity.


Case Overview: A 73-Year-Old Male With Urothelial Carcinoma

Initial presentation

  • A 73-year-old man presents with LUTS with intermittent hematuria
  • PMH: HTN, well-controlled on an ARB; mild hepatic and renal impairment
  • PE: distension of bladder; slow flow on voiding

Clinical workup

  • Labs: Hb 11.4 g/dl, WBC 3.5 x 109/L, AST and ALT: ~4x ULN, CrCl: 35 mL/min; others WNL
  • Cystoscopy: showed a 2.6 cm mass around the neck of the bladder
  • TURBT was performed; transition cell carcinoma of the urothelium, with tumor invading the perivesical tissue
  • Chest/abdomen/pelvic CT scan: large bladder mass, evidence of multiple regional lymph nodes involved (perivesical and sacral), and a 2.3 cm mass in the left upper lobe
  • Stage IIIB; ECOG PS 1

Treatment

  • Patient received 6 cycles of carboplatin + gemcitabine; achieved partial response
  • CT abdomen/pelvis showed decrease size in bladder mass, nodal findings mildly improved, no evidence of new disease
  • Initiated avelumab 10 mg/kg IV q2W as maintenance therapy

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