A 56-year-old woman was referred to our institution for a left nephroureterectomy after the diagnoses of a nonfunctioning left kidney and noninvasive papillary urothelial carcinoma of the distal left ureter (Ta grade 1). Following the procedure, surveillance cystoscopy and computed tomography (CT) scan of the abdomen and pelvis demonstrated a large bladder tumor with pan-urothelial extension. A transurethral resection of bladder tumor (TURBT) revealed low-grade papillary urothelial carcinoma without muscle invasion. The patient underwent a cystectomy with a continent ileal diversion to the urethra (neobladder). Approximately 10 months later, a 1.3 × 1.1 cm nodule in the upper lobe of her left lung was seen on CT scan. A video-assisted thoracoscopic surgery (VATS) wedge excision was performed of that lesion. Pathologic evaluation of the lung specimen revealed findings most consistent with low-grade metastatic urothelial carcinoma. Five cycles of a platinum-based regimen were administered after the resection.
What did the pathologic examination of the left nephroureterectomy and subsequent cystectomy reveal?
Dr. Francisco G. La Rosa: This patient shows a very rich surgical pathology history of the urinary tract. Our pathology examination of the left nephrectomy and left ureter specimens revealed a multifocal low-grade urothelial carcinoma present both at the renal pelvis and at the distal portion of the ureter (Figure 1A) and involving the distal ureteral surgical margin. Both of these tumors showed a papillary configuration and were limited to the mucosal surface, thus indicating no evidence of invasion. Three months later, a CT scan showed wide involvement of the urinary bladder by tumor, and tissue from the TURBT revealed low-grade papillary urothelial carcinoma. Following radical cystectomy, examination of the bladder showed a low-grade urothelial carcinoma, but this time with clear evidence of invasion deep into the muscularis propria (American Joint Committee on Cancer [AJCC] stage II: pT2b, N0, MX; Figure 1B) and with multifocal lymphovascular invasion (Figure 1C).
What are the indications for performing a radical cystectomy on a low-grade urothelial carcinoma?
Dr. Shandra Wilson: Indications for cystectomy include stage II–IV bladder cancer, with stage II demonstrating muscularis propria invasion. Radical cystecomy is rare for low-grade cancer. This patient is the only case in 6 years in which we have done a radical cystectomy because of a low-grade urothelial carcinoma. Usually, low-grade urothelial cancers do not tend to become muscle invasive. Alternatively, if tumors recur quickly or cover the entire bladder, then cystectomy is considered. Our patient had both of the latter two conditions.
Dr. Al B. Barqawi: I agree. In this case, the cystectomy specimen revealed a concealed muscle invasive tumor that was missed on the TURBT. A recent review of the literature reported that prior history of transitional cell carcinoma combined with upper tract tumor multifocality were the most frequently reported risk factors for bladder tumors following upper urinary tract urothelial cell carcinomas, which was consistent with this case recurrence.
How often is upper urinary tract cancer associated with urinary bladder cancer?
Dr. Wilson: Urothelial carcinoma is the most prevalent cancer in the upper urinary tract, but only accounts for approximately 5% of all urothelial carcinomas. These upper-tract cancers are thought to be seeding tumors, and various studies have demonstrated the presence of urinary bladder cancer in 15% to 75% of patients within 5 years following an upper-tract diagnosis.
How does metastatic urothelial carcinoma differ in radiologic appearance in the lung vs a primary lung lesion? Dr. Kimi L. Kondo: There is no specific radiologic characteristic that uniquely distinguishes a urothelial metastasis to the lung from a primary lung cancer. Pulmonary metastases tend to present as multiple lesions, although 5% of all solitary lung nodules are metastatic. Metastases typically have sharp margins and are usually located peripherally and in the lung bases; however, primary lung cancers can also have these characteristics. Nodules with increased 18F-fluorodeoxyglucose (FDG) uptake on positron-emission tomography (PET) are usually thought to be malignant, but inflammatory and infectious processes also can have increased FDG uptake. Biopsy and pathologic analysis are needed to distinguish a urothelial metastasis from a primary lung cancer. In our patient, the CT scan of the chest revealed a nodule with a corresponding hypermetabolic lesion on the FDG-PET scan (Figures 2A, 2B).
The metastatic pulmonary nodule was detected by FDG-PET scan and showed hypermetabolic signs. Is there a role for PET imaging in urothelial carcinoma?
Dr. Thomas W. Flaig: In patients with metastatic disease, I generally initiate staging with a CT scan of the chest, abdomen, and pelvis plus a whole-body bone scan. In this case, an FDG-PET scan demonstrates the malignant deposit in her lung. There are limited data on the usefulness of PET scanning in urothelial cancer. However, the utility of PET scanning was recently examined preoperatively in patients with bladder cancer planning for cystectomy. Occult metastatic disease was detected in 7 of the 42 subjects with negative CT imaging, yielding a sensitivity of 70% and specificity of greater than 90%. This suggests a potential role for PET imaging in urothelial cancer. What has your experience been with resecting metastatic transitional cell carcinoma in the lung?
Dr. J.D. Mitchell: Consultation for metastatic transitional cell carcinoma to the lung is unusual. In my experience, the metastatic nodules attributed to urothelial carcinoma within the lung are typically few in number, peripheral, and amenable to wedge excision.
1. Azémar MD, Comperat E, Richard F, et al: Bladder recurrence after surgery for upper urinary tract urothelial cell carcinoma: Frequency, risk factors, and surveillance. Urol Oncol Sept 15, 2009 (epub ahead of print).
2. Munoz JJ, Ellison LM: Upper tract urothelial neoplasms: Incidence and survival during the last 2 decades. J Urol 164:1523-1525, 2000.
3. Flanigan RC: Urothelial tumors of the upper tract, in Wein AJ, Kavoussi LR, Novick AC, et al (eds): Campbell-Walsh Urology, 9th ed, vol 2, p 1640. Philadelphia, Saunders, 2007.
4. Kibel AS, Dehdashti F, Katz MD, et al: Prospective study of [18F]fluorodeoxyglucose positron emission tomography/computed tomography for staging of muscle-invasive bladder carcinoma. J Clin Oncol 27:4314-4320, 2009.
5. Ginsberg RJ, Rubinstein LV: Randomized trial of lobectomy versus limited resection for T1N0 non-small cell cancer by the Lung Cancer Study Group. Ann Thorac Surg 60:
6. El-Sherif A, Gooding WE, Santos R, et al: Outcomes of sublobar resection versus lobectomy for stage I non-small cell lung cancer: A 13-year analysis. Ann Thorac Surg 82:408-415, 2006.
7. Nakamura H, Kawasaki N, Taguchi M, et al: Survival following lobectomy vs limited resection for stage I lung cancer: A meta-analysis. Br J Cancer 92:1033-1037, 2005.
8. Dougherty DW, Gonsorcik VK, Harpster LE, et al: Superficial bladder cancer metastatic to the lungs: Two case reports and review of the literature. Urology 73(1):210.e3-e5, 2009.
9. Sternberg CN, Yagoda A, Scher HI, et al: Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium. J Urol 133:403-407, 1985.
10. von der Maase H, Sengelov L, Roberts JT, et al: Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23:4602-4608, 2005.
11. Hussain M, Vaishampayan U, Du W, et al: Combination paclitaxel, carboplatin, and gemcitabine is an active treatment for advanced urothelial cancer. J Clin Oncol 19:2527-2533, 2001.