genitourinary disorders
Renal Cell Carcinoma
Treatment of Renal Cancer
For early renal cell carcinoma (RCC), surgical treatment, active surveillance, or thermal ablation For advanced RCC, palliative therapies or experimental protocols Radical nephrectomy (removal of kidney, perirenal fat, Gerota fascia +/- ipsilateral adrenal gland) is standard treatment for localized RCC and provides a reasonable chance for cure. Results with open or minimally invasive procedures are comparable; recovery is generally easier with minimally invasive procedures. Nephron-sparing surgery (partial nephrectomy) is possible and appropriate for many patients. Partial nephrectomy is gaining popularity because it results in a lower incidence of Chronic Kidney Disease than radical nephrectomy. It is the standard of care for clinically staged T1a tumors (cT1a, Nonsurgical destruction of renal tumors via freezing (cryosurgery) or thermal energy (radiofrequency ablation), often percutaneously, should be considered for tumors smaller than 3 cm. For small renal masses, active surveillance (with delayed intervention) should be considered a first-line treatment option, particularly if active treatments pose risks and/or patients have significant comorbidities. Decision-making for treatment is complex and multifactorial and typically involves shared decision-making ( Treatment references ). For tumors involving the renal vein and vena cava, surgery may be curative if no nodal or distant metastases exist. If both kidneys are affected, partial nephrectomy of one or both kidneys is preferable to bilateral radical nephrectomy if technically feasible. in S-TRAC led to its approved use following resection in high-risk patients ( Treatment references ). Its use has been limited. The KEYNOTE-564 study ( Palliation can include nephrectomy, tumor embolization, external beam radiation therapy and systemic therapy. Resection of metastases offers palliation and, if metastases are limited in number, prolongs life in some patients, particularly those with a long interval between initial treatment (nephrectomy) and development of metastases. Although metastatic RCC is traditionally characterized as radioresistant, radiation therapy can be palliative when RCC is oligometastatic, particularly to the bone. Systemic therapies are the mainstay of management of patients with metastatic RCC. Drug therapy reduces tumor size and prolongs life. About 10 to 20% of patients respond tointerferon alfa-2bor IL-2, although the response is long-lasting in<5%. Many targeted therapies have shown efficacy for advanced tumors:sunitinib,sorafenib,bevacizumab,pazopanib,cabozantinib,axitinib, andlenvatinib(tyrosine kinase inhibitors) andtemsirolimusandeverolimus, which inhibit the mammalian target of rapamycin (mTOR). However, the newest available systemic therapies for metastatic RCC are immune checkpoint inhibitors (ICI). These monoclonal antibodies against PD-1 or PD-L1 work by blocking the PD-1/PD-L1 interaction between tumor cells and infiltrating T-cells, thus blocking PD-1 pathway-mediated inhibition of the immune response, including the antitumor immune response. For favorable and intermediate or poor-risk RCC, first-line treatments are combination therapies (ICI +/- targeted therapy, chemotherapy, or a 2nd ICI); combinations includeaxitinib+pembrolizumab,cabozantinib+nivolumab, levantinib +pembrolizumab, andipilimumab+nivolumab. Other treatments are experimental. They include Hematopoietic Stem Cell Transplantation , other interleukins, anti-angiogenesis therapy (eg, alone ( Treatment references ); however, that trial was criticized for its patient selection (heavily enriched with poor-risk patients with minimal inclusion of intermediate-risk patients). The current recommendations are to consider cytoreductive nephrectomy in patients with any of the following criteria: The bulk of the disease burden in the kidney Symptomatic bleeding or pain from the primary tumor Presence of a paraneoplastic tumor Excellent performance status with normal contralateral kidney function Increased knowledge of genetic subtypes of RCC is leading to evolving management recommendations that are more specific. 1.Chandrasekar T, Boorjian SA, Capitanio U, et al: Collaborative review: Factors influencing treatment decisions for patients with a localized solid renal mass.Eur Urol80(5):575-588, 2021. doi: 10.1016/j.eururo.2021.01.021 2.Ravaud A, Motzer RJ, Pandha HS et al: Adjuvantsunitinibin high-risk renal-cell carcinoma after nephrectomy.N Engl J Med8;375(23):2246-2254, 2016. doi: 10.1056/NEJMoa1611406 3.Choueiri TK, Tomczak P, Park SH, et al for the KEYNOTE-564 Investigators: Adjuvantpembrolizumabafter nephrectomy in renal-cell carcinoma.N Engl J Med385(8):683-694, 2021. doi: 10.1056/NEJMoa2106391 4.Mejean A, Ravaud A, Thezenas S, et al:Sunitinibalone or after nephrectomy in metastatic renal-cell carcinoma.N Eng J Med379:417-427, 2018. doi: 10.1056/NEJMoa1803675 