Chapter 090. Bladder and Renal Cell Carcinomas (Part 7) pptx

Chapter 090. Bladder and Renal Cell Carcinomas (Part 7) Renal Cell Carcinoma: Treatment Localized Tumors The standard management for stage I or II tumors and selected cases of stage III disease is radical nephrectomy. This procedure involves en bloc removal of Gerota's fascia and its contents, including the kidney, the ipsilateral adrenal gland, and adjacent hilar lymph nodes. The role of a regional lymphadenectomy is controversial. Extension into the renal vein or inferior vena cava (stage III disease) does not preclude resection even if cardiopulmonary bypass is required. If the tumor is resected, half of these patients have prolonged survival. Nephron-sparing approaches via open or laparoscopic surgery may be appropriate for patients who have only one kidney, depending on the size and location of the lesion. A nephron-sparing approach can also be used for patients with bilateral tumors, accompanied by a radical nephrectomy on the opposite side. Partial nephrectomy techniques are being applied electively to resect small masses for patients with a normal contralateral kidney. Adjuvant therapy following this surgery does not improve outcome, even in cases with a poor prognosis. Advanced Disease Surgery has a limited role for patients with metastatic disease. However, long-term survival may occur in patients who relapse after nephrectomy in a solitary site that can be removed. One indication for nephrectomy with metastases at initial presentation is to alleviate pain or hemorrhage of a primary tumor. Also, a cytoreductive nephrectomy before systemic treatment improves survival for carefully selected patients with stage IV tumors. Metastatic renal cell carcinoma is highly refractory to chemotherapy and only infrequently responsive to cytokine therapy with IL-2 or IFN-α. IFN-α and IL-2 produce regressions in 10–20% of patients, but on occasion these responses are durable. IL-2 was approved on the observation of durable complete remission in a small proportion of cases. The situation changed dramatically when two large-scale randomized trials established a role for antiangiogenic therapy in this disease as predicted by the genetic studies. These trials separately evaluated two orally administered antiangiogenic agents, sorafenib and sunitinib, that inhibited receptor tyrosine kinase signaling through the VEGF and PDGF receptors. Both showed efficacy as second-line treatment following progression during cytokine treatment, resulting in approval by regulatory authorities for the treatment of advanced renal cell carcinoma. A randomized phase 3 trial comparing sunitinib to IFN-α showed superior efficacy for sunitinib with an acceptable safety profile. The trial resulted in a change in the standard first-line treatment from IFN to sunitinib. Sunitinib is usually given orally at a dose of 50 mg/d for 4 weeks out of 6. Diarrhea is the main toxicity. Sorafenib is usually given orally at a dose of 400 mg bid. In addition to diarrhea, toxicities include rash, fatigue, and hand-foot syndrome. Temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor, also has activity in previously treated patients. The usual dosage is 25 mg IV weekly. The prognosis of metastatic renal cell carcinoma is variable. In one analysis, no prior nephrectomy, a KPS <80, low hemoglobin, high corrected calcium, and abnormal lactate dehydrogenase were poor prognostic factors. Patients with zero, one or two, and three or more factors had a median survival of 24, 12, and 5 months, respectively. These tumors may follow an unpredictable and protracted clinical course. It may be best to document progression before considering systemic treatment. Further Readings Black PC et al: Molecular markers of urothelial cancer and their use in the monitoring of superficial urothelial cancer. J Clin Oncol 24:5528, 2006 [P MID: 17158538] Brassell SA, Kamat AM: Contemporary intravesical treatment options for urothelial carcinoma of the bladder. J Natl Compr Canc Netw 4:1027, 2006 [PMID: 17112451] Cohen HT, McGovern FJ: Renal- cell carcinoma. N Engl J Med 353:2477, 2005 [PMID: 16339096] Huang WC et al: Chronic kidney disease after nephrectomy in patients with renal cortical tumours: A retrospective cohort study. Lancet Oncol 7:735, 2006 [PMID: 16945768] Mitra AP et al: Molecular pathways in invasive bladder cancer: New i nsights into mechanisms, progression, and target identification. J Clin Oncol 24:5552, 2006 [PMID: 17158541] Motzer RJ et al: Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295:2516, 2006 [PMID: 16757724] Nelson EC et al: Renal cell c arcinoma: Current status and emerging therapies. Cancer Treat Rev 33:299, 2007 [PMID: 17329029] Sugano K, Kakizoe T: Genetic alterations in bladder cancer and their clinical applicati ons in molecular tumor staging. Nature Clin Pract 3:642, 2006 [PMID: 17149381] Winquist E et al: Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: A systematic review and meta- analysis. J Urol 171:561, 2004 [PMID: 14713760] Bibliography Advanced Bladder Cancer Meta- Analysis Collaboration: Neoadjuvant chemotherapy in invasive bladder cancer: A systematic review and meta- analysis. Lancet 361:1927, 2003 . Chapter 090. Bladder and Renal Cell Carcinomas (Part 7) Renal Cell Carcinoma: Treatment Localized Tumors The standard management for stage I or II tumors and selected cases. fascia and its contents, including the kidney, the ipsilateral adrenal gland, and adjacent hilar lymph nodes. The role of a regional lymphadenectomy is controversial. Extension into the renal. EC et al: Renal cell c arcinoma: Current status and emerging therapies. Cancer Treat Rev 33:299, 2007 [PMID: 17329029] Sugano K, Kakizoe T: Genetic alterations in bladder cancer and their clinical