Renal Cell Carcinoma

Information from the evaluation makes preliminary staging possible. The TNM (tumor, node, metastasis) system has been recently refined to be precise (see tables AJCC/TNM Staging of Renal Cell Carcinoma AJCC/TNM* Staging of Renal Cell Carcinoma and TNM Definitions for Renal Cell Carcinoma TNM Definitions for Renal Cell Carcinoma ). At diagnosis, RCC is localized in 45%, locally invasive in about 33%, and spread to distant organs in 25% of patients.

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 Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more than radical nephrectomy. It is the standard of care for clinically staged T1a tumors (cT1a, < 4 cm) and should be considered in patients with T1b or T2 tumors and those with absolute indications for nephron preservation (eg, bilateral renal masses, CKD, solitary kidney). Radical nephrectomy should be considered in patients with a normal contralateral kidney, normal kidney function, and more advanced primary tumors (cT1b through cT4). 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 (1 Treatment references Renal cell carcinoma (RCC) is the most common renal cancer. Symptoms can include hematuria, flank pain, a palpable mass, and fever of unknown origin (FUO). However, symptoms are often absent... read more ).

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.

Adjuvant use of targeted therapy after surgery has failed to prolong survival in multiple clinical trials, yet improvements in disease-free survival seen in patients taking adjuvant sunitinib in S-TRAC led to its approved use following resection in high-risk patients (2 Treatment references Renal cell carcinoma (RCC) is the most common renal cancer. Symptoms can include hematuria, flank pain, a palpable mass, and fever of unknown origin (FUO). However, symptoms are often absent... read more ). Its use has been limited. The KEYNOTE-564 study (3 Treatment references Renal cell carcinoma (RCC) is the most common renal cancer. Symptoms can include hematuria, flank pain, a palpable mass, and fever of unknown origin (FUO). However, symptoms are often absent... read more ) showed robust increases in disease-free survival in patients treated with pembrolizumab as an adjuvant therapy for surgically treated RCC patients at high risk of recurrence.

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 were the mainstay of management of patients with metastatic RCC. Drug therapy reduces tumor size and prolongs life. About 10 to 20% of patients respond to interferon alfa-2b or 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, and lenvatinib (tyrosine kinase inhibitors) and temsirolimus and everolimus, 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 or a 2nd ICI) ; combinations include axitinib + pembrolizumab, cabozantinib + nivolumab, levantinib + pembrolizumab, and ipilimumab + nivolumab.

Other treatments are experimental. They include stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more , other interleukins, anti-angiogenesis therapy (eg, thalidomide), and vaccine therapy. Traditional chemotherapeutic drugs, alone or combined, and progestins are ineffective.

Cytoreductive nephrectomy before systemic therapy is controversial now that CARMENA (Clinical Trial to Assess the Importance of Nephrectomy), a randomized phase III trial comparing cytoreductive nephrectomy followed by sunitinib and sunitinib alone showed survival was not worse when treating with sunitinib alone (4 Treatment references Renal cell carcinoma (RCC) is the most common renal cancer. Symptoms can include hematuria, flank pain, a palpable mass, and fever of unknown origin (FUO). However, symptoms are often absent... read more ); however, that trial was criticized for its patient selection.

The current recommendations are to consider cytoreductive nephrectomy in patients with any of the following criteria:

Increased knowledge of genetic subtypes of RCC is leading to evolving management recommendations that are more specific.