Criteria

RCC is diagnosed by a combination of imaging and pathology to confirm malignancy, and to stage patients both clinically and pathologically.

TNM staging of RCC[7][8]

The TNM classification describes the extent of disease based on the following anatomic factors:

  • size and extent of the primary tumor (T)

  • regional lymph node involvement (N); and

  • presence or absence of distant metastases (M).

Staging

  • Early-stage RCC (stages 1 and 2) is defined as tumor confined to kidney without regional lymph node or distant metastasis.

  • Stage 3 tumors extend into major veins, or invade the adrenal gland or perinephric tissue, but do not invade beyond the Gerota fascia. There may be metastasis in a single regional lymph node, but no evidence of distant metastasis.

  • Stage 4 tumors extend beyond the Gerota fascia or have distant metastasis.

Prognostic criteria

Prognostic models have been developed to integrate these diagnostic findings into a schema that includes other patient factors, and that may better predict for survival or prognosis than classic staging; however, the utility of these models to date has largely been for stratifying patients into clinical trials.

The UCLA Integrated Staging System and SSIGN (Mayo) algorithms can be applied to patients with early localized disease, postnephrectomy.[74][75]

The Memorial Sloan Kettering Cancer Center (MSKCC) model is one of the more widely used prognostic models in metastatic disease, and has been well validated.[60] Further prognostic criteria for patients with metastatic RCC treated with sunitinib, sorafenib, and bevacizumab have been elucidated, in addition to validation of some of the MSKCC criteria.[76] This study found that hemoglobin less than the lower limit of normal, corrected calcium greater than the upper limit of normal (ULN), Karnofsky performance status less than 80%, time from diagnosis to treatment of less than 1 year, lactate dehydrogenase greater than 1.5 times the ULN, neutrophils greater than the ULN, and platelets greater than the ULN were independent adverse prognostic factors.[76]

The other most commonly used risk stratification score is the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria, which includes neutrophilia and thrombocytosis.[77]

Predictors of poor survival are:[77] 

  • Karnofsky performance status of less than 80%

  • Less than 1 year from diagnosis to treatment

  • Anemia (hemoglobin concentration less than the lower limit of normal)

  • Hypercalcemia (corrected calcium concentration greater than the ULN)

  • Neutrophilia (neutrophil count greater than the ULN)

  • Thrombocytosis (platelet count greater than the ULN).

Risk groups in the MSKCC and IMDC models are categorized as:[77]

  • Favorable: 0 prognostic factors

  • Intermediate: 1-2 prognostic factors

  • Poor: ≥3 prognostic factors.

A novel risk scoring system for patients with metastatic RCC treated with immune checkpoint inhibitors has been proposed, and includes monocyte‐to‐lymphocyte ratio, BMI, and number and sites of metastases at baseline; however, this is awaiting validation.[78]

Molecular profiling and biomarkers

The effort to integrate molecular profiling and biomarkers into prognostic models continues, particularly for metastatic disease. Several molecular biomarkers are emerging as potential correlates of disease extent, prognosis, predictive markers of response to therapy, and even as potential therapeutic targets.[2] Current biomarkers of interest include plasma protein levels of vascular endothelial growth factor, hypoxia induced factor, tissue inhibitor of metalloproteinase 1; various genetic mutations such as in VHL, ras p21, pTEN loss, and chromosomal abnormalities such as loss of 9p; and tumor expression of cell death-related molecules (programmed death 1, programmed cell death 1 ligand 1, cytotoxic T-lymphocyte-associated protein-4).[79][80][81]

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