Accounts over 70% of all renal cell cancers.
Small clear cell renal cell cancers of less than 4 cm exhibit a relatively indolent behavior, but a small subset of these tumors are aggressive.
Surgery is the treatment of choice for localized or locoregional disease stages I- III.
Up to 25% of patients with localized disease relapse after surgery.
15% of patients present with metastatic disease.
The five-year survival rate for metastatic renal cell cancer is about 10%, but recent immunotherapy has extended this time.
Clear cell renal cancer can spread through both lymphatics and hematogenously.
This cell type is predisposed to intravascular growth.
It can colonize at a wide range of secondary distance sites.
Liver metastases are associated with the worst prognosis, while pancreatic metastasis has a good prognosis.
Metastases may be solitary or oligometastatic with long latency periods or associated with multi organ dissemination.
Isolated metastases can be treated with surgery, ablation or stereotactic radiation, or by active surveillance.
Sporadic clear-cell renal carcinoma is characterized by VHL mutation in greater than 80% of tumors and loss of heterozygosity of 3P in about 90% of cases.
Most metastatic Clear cell renal carcinomas harbor mutations in the von Hippel Lindau tumor suppressor genes.
Loss of the Von Hippel Lindau tumor suppressor gene occurs in up to 90% of clear cell, renal cell tumors, and VHL inactivation leads to activation of hypoxia and angiogenesis pathways.
The deficient production of short find Hippel-Lindau proteins reduces ubiquitination of hypoxia inducible factor alpha resulting in increased transcription of angiogenic, proliferative and metabolic genes in normoxia.
Adjuvant Pembrolizumab should be considered for patients with intermediate or high risk operable clear cell renal cell cancer.
Systemic therapy with programmed cell protein 1 (PD –1) based combination therapy is the standard of care for patients who relapse within one year of nephrectomy.
Metastatectomy as an alternative to systemic therapy in patients with synchronous or early oligometastatic disease is not usually recommended.
Adjuvant Pembrolizumab can be offered to patients after complete resection of oligometastatic disease.
Keynote-564 showed that Pembrolizumab versus placebo as post-nephrectomy therapy for high risk clear cell renal carcinoma showed a benefit-hazard ratio 0.63.