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

Renal Cell Carcinoma: TreatmentLocalized 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 Gerotas 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...
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Chapter 090. Bladder and Renal Cell Carcinomas (Part 7) 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 ofstage III disease is radical nephrectomy. This procedure involves en bloc removalof Gerotas fascia and its contents, including the kidney, the ipsilateral adrenalgland, and adjacent hilar lymph nodes. The role of a regional lymphadenectomy iscontroversial. Extension into the renal vein or inferior vena cava (stage III disease)does not preclude resection even if cardiopulmonary bypass is required. If thetumor is resected, half of these patients have prolonged survival. Nephron-sparing approaches via open or laparoscopic surgery may beappropriate for patients who have only one kidney, depending on the size andlocation of the lesion. A nephron-sparing approach can also be used for patientswith bilateral tumors, accompanied by a radical nephrectomy on the opposite side.Partial nephrectomy techniques are being applied electively to resect small massesfor patients with a normal contralateral kidney. Adjuvant therapy following thissurgery 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 asolitary site that can be removed. One indication for nephrectomy with metastasesat initial presentation is to alleviate pain or hemorrhage of a primary tumor. Also,a cytoreductive nephrectomy before systemic treatment improves survival forcarefully selected patients with stage IV tumors. Metastatic renal cell carcinoma is highly refractory to chemotherapy andonly infrequently responsive to cytokine therapy with IL-2 or IFN-α. IFN-α andIL-2 produce regressions in 10–20% of patients, but on occasion these responsesare durable. IL-2 was approved on the observation of durable complete remissionin a small proportion of cases. The situation changed dramatically when two large-scale randomized trialsestablished a role for antiangiogenic therapy in this disease as predicted by thegenetic studies. These trials separately evaluated two orally administeredantiangiogenic agents, sorafenib and sunitinib, that inhibited receptor tyrosinekinase signaling through the VEGF and PDGF receptors. Both showed efficacy assecond-line treatment following progression during cytokine treatment, resultingin approval by regulatory authorities for the treatment of advanced renal cellcarcinoma. A randomized phase 3 trial comparing sunitinib to IFN-α showedsuperior efficacy for sunitinib with an acceptable safety profile. The trial resulted in a change in the standard first-line treatment from IFNto sunitinib. Sunitinib is usually given orally at a dose of 50 mg/d for 4 weeks outof 6. Diarrhea is the main toxicity. Sorafenib is usually given orally at a dose of400 mg bid. In addition to diarrhea, toxicities include rash, fatigue, and hand-footsyndrome. Temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor,also has activity in previously treated patients. The usual dosage is 25 mg IVweekly. The prognosis of metastatic renal cell carcinoma is variable. In oneanalysis, no prior nephrectomy, a KPS protracted clinical course. It may be best to document progression beforeconsidering systemic treatment. Further Readings Black PC et al: Molecular markers of urothelial cancer and their use in themonitoring of superficial urothelial cancer. J Clin Oncol 24:5528, 2006 [PMID:17158538] Brassell SA, Kamat AM: Contemporary intravesical treatment options forurothelial 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 withrenal cortical tumours: A retrospective cohort study. Lancet Oncol 7:735, 2006[PMID: 16945768] Mitra AP et al: Molecular pathways in invasive bladder cancer: Newinsights into mechanisms, progression, and target identification. J Clin Oncol24:5552, 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 carcinoma: Current status and emergingtherapies. Cancer Treat Rev 33:299, 2007 [PMID: 17329029] Sugano K, Kakizoe T: Genetic alterations in bladder cancer and theirclinical applications in molecular tumor staging. Nature Clin Pract 3:642, 2006[PMID: 17149381] Winquist E et al: Neoadjuvant chemotherapy for transitional cell carcinomaof the bladder: A systematic review and meta-analysis. J Urol 171:561, 2004[PMID: 14713760] Bibliography Advanced Bladder Cancer Meta-Analysis Collaboration: Neoadjuvantchemotherapy in invasive bladder cancer: A systematic review and meta-analysis.Lancet 361:1927, 2003