How do the surgical margins differ when resecting a metastatic lesion in the lung vs a primary lesion?
Dr. Mitchell: When resecting metastatic disease that has spread to the lung, our main goal is complete excision of the lesion with a negative margin. In most cases, this is accomplished with simple wedge excision through a VATS approach. In rare cases, metastatic lesions are not amenable to simple wedge excision, requiring segmentectomy or even lobectomy for complete removal. In modern surgical practice, this too should be done through a VATS approach whenever feasible. Complete removal of all identifiable metastatic lesions is key to the success of the procedure.
In contrast, primary lung cancers are treated preferentially with anatomic lung resection, typically lobectomy, based on data from the Lung Cancer Study Group demonstrating improved local control and a trend toward improved survival with lobectomy compared with sublobar resection.[5] This approach has been challenged in recent years, with excellent results reported in several single-institution studies using sublobar resection for small (< 2 cm) non–small-cell lung cancers.[6,7] A nationwide randomized trial (Cancer and Leukemia Group B [CALGB] 140503) is currently underway, comparing survival and local recurrence rates after lobar vs sublobar resection for lung cancers smaller than 2 cm.
Were there any indications from the nephroureterectomy or bladder pathology that may have suggested future metastasis to the lung?
Urothelial Metastasis to the LungDr. La Rosa: Figure 3 demonstrates the urothelial metastasis in the lung. The most evident correlation between the urothelial tumors and the presence of this lung metastasis is the presence of tumor invasion into the muscularis propria and lymphovascular invasion as revealed in the urinary bladder specimen. It is difficult to speculate whether the tumors in the renal pelvis and ureter—which did not show evidence of invasion—had anything to do with this metastasis. Nevertheless, the tumors in all specimens, including the lung metastasis, looked very similar and had the characteristics of low-grade urothelial carcinomas; only a molecular analysis could establish differences between them. Some patients with very limited and noninvasive tumors may present with distant metastasis later in life.[8] However, the presence of muscularis propria invasion and lymphovascular invasion in the bladder specimen make the possibility of distant metastasis most likely.
Would chemotherapy be indicated at this time?
Dr. Flaig: Urothelial carcinoma is a chemotherapy-sensitive cancer. Modern, multidrug chemotherapy regimens have been built around cisplatin(Drug information on cisplatin), the most active drug in bladder cancer. For many years, our standard approach included the use of the MVAC regimen (methotrexate, vinblastine(Drug information on vinblastine), doxorubicin(Drug information on doxorubicin), and cisplatin).[9] In the past few years, the activity of gemcitabine(Drug information on gemcitabine) (Gemzar) in urothelial carcinoma was recognized. A prospective, randomized comparison of MVAC vs gemcitabine with cisplatin (GC) was performed in patients with advanced urothelial cancer.[10] While the overall 5-year survival was approximately 15% in both arms, many now favor GC over MVAC due to its improved tolerability.
In this case, we have pathologically proven metastatic disease with a suspicious lesion in the pelvis after radical cystectomy for urothelial cancer. The patient’s options at this point would include systemic chemotherapy or observation. The rationale for offering chemotherapy now would be to delay the recurrence of symptomatic metastatic disease. Give the patient’s renal insufficiency, we may have to consider a non–cisplatin-based regimen. Recent measurements of her serum creatinine have ranged from 1.6 to 1.8 mg/dL, and I would estimate her creatinine clearance to be approximately 60 mL/min. An alternative regimen in this setting would include the combination of carboplatin(Drug information on carboplatin), paclitaxel(Drug information on paclitaxel), and gemcitabine. In the first-line setting, this combination yields an objective response in two-thirds of patients, with approximately half of these being complete responses.[11]
Summary
This 56-year-old patient was initially found to have a papillary, noninvasive, low-grade urothelial carcinoma in the upper urinary tract, which resulted in an obstructive nonfunctioning kidney and a subsequent nephroureterectomy. The carcinoma then manifested in the urinary bladder, and a radical cystectomy was performed. The histology of the urinary bladder revealed low-grade urothelial carcinoma with lymphovascular invasion. Upon PET/CT scan surveillance, a suspicious nodule was found in the upper lobe of the left lung. The patient underwent a left VATS excision that confirmed metastatic low-grade urothelial carcinoma. The patient received five cycles of platinum-based chemotherapy and surveillance imaging with clinic follow-up continued.
Outcome
The patient completed CT scans every 3 months. Upon surveillance, a slow-growing nodule (less than 1cm) was found in each lung, and these were followed conservatively with CT scans. Also, an 11 × 6 cm complex pelvic mass with fluid collection was present on CT scan. The patient underwent an abdominal exploration with removal of the pelvic mass, drainage of fluid, lymph node dissection, and right oopherectomy. The pathology of the mass revealed papillary noninvasive low-grade urothelial carcinoma without lymph node involvement. Three months later, a new suspicious lung nodule was present in the upper lobe of the right lung, while the existing nodules did not show significant changes.
Management Plan
The patient will continue to undergo surveillance CT scans with clinic follow-up every 3 months. Systemic therapy will be reinstituted if significant growth of the pulmonary nodules occurs or the patient has any clinical symptoms. If either of these situations occur, options would include a retrial of carboplatin/docetaxel or a phase I (early human) clinical trial of an investigational agent.
Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
