Prognosis

The overall 5-year survival is around 78%, but this depends largely on stage at diagnosis, as well as on established prognostic factors.[19] Five-year relative survival by stage at diagnosis (kidney and renal pelvis cancer, 2014-2020 data):[19]

  • Localized 93.3%

  • Regional 75.1%

  • Distant 18.2%

The advent of targeted treatments and immune checkpoint inhibition for advanced disease is continuing to improve the outlook for RCC. Patients who experience symptoms on presentation have poorer prognosis.[16] Prognosis is particularly poor in those who develop paraneoplastic syndromes.[18]

Tumor histology subtypes can indicate varying prognoses, but when adjusted for stage and tumor grade, this may become less relevant. Clear-cell histology may, in general, be associated with poorer prognosis; in addition, sarcomatoid differentiation in any histology tends to dictate a more aggressive tumor.[37] Overall, pathologic and clinical staging, as well as certain patient characteristics, are included in prognostic models.

Prognostic models

RCC is diagnosed by a combination of imaging and pathology to confirm malignancy, and to stage patients both clinically and pathologically.[7][8] 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.[74][75][77] The effort to integrate molecular profiling and biomarkers into prognostic models continues.

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 original diagnosis to treatment of less than 1 year, 2 or more organ sites of metastatic disease, neutrophils greater than the ULN, and platelets greater than the ULN were independent adverse prognostic factors.[76] Patients were segregated into three risk categories: favorable-risk group (no prognostic factors), in which median overall survival (mOS) was not reached and 2-year OS (2y OS) was 75%; intermediate-risk group (1 or 2 prognostic factors), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (3 to 6 prognostic factors), in which mOS was 8.8 months and 2y OS was 7%.[76]

The other most commonly used risk stratification score is the International Metastatic Renal Cell Carcinoma Database Consortium criteria, which includes neutrophilia and thrombocytosis. Predictors of poor survival are:

  • 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).[77]

Early-stage RCC prognosis

Early-stage disease in general has excellent prognosis, with greater than 95% cancer-specific survival among all management strategies (median follow-up 22 to 120 months).[4] Increasing age, larger tumor size and higher tumor grade were the most common predictors of worse cancer-specific survival.[88] 

Risk of local relapse after adequate curative surgery for small renal tumors is rare (up to 2%) and is unlikely after 5 years.[174] However, between 20% to 30% of patients with localized disease who undergo curative surgery will develop recurrent or metastatic disease within 5 years.[175]

Advanced stage/metastatic RCC prognosis

In one study in patients diagnosed with locally advanced disease, the 10-year progression-free survival for those with T3 clear cell tumors was 72%.[176]

The median overall survival of untreated metastatic disease is 5 months; this improved to 10.2 months in the cytokine era, and to 17.7 months when treated with targeted molecular therapy.[177] Specifically, evidence has demonstrated a near doubling of overall survival since the general availability of sunitinib for metastatic RCC.[178] The COMPARZ data from patients treated with pazopanib or sunitinib estimated median of favorable risk group at approximately 42 months, intermediate-risk group at approximately 26 months, and poor risk group at less than 1 year.[120] The advent of immune checkpoint inhibitors and combinations of therapies has led to prolonged disease control in some patients and use of older median overall survival data is no longer completely applicable.[80][179]

Metachronous metastases (recurrent metastatic disease diagnosed at a later time) fare better than synchronous metastases (metastases diagnosed in separate sites at the same time), and there is evidence to support repeat metastasectomy.[180] Patients with the best prognoses are those with a long disease-free interval since original diagnosis (>12 months), R0 resections (no residual microscopic tumor cells remaining in tumor bed; surgical resection margins on pathology are completely negative [i.e., clear of tumor]), and no more than 6 metastases.[180][181] Survival at 5 years has been found to range from 30% to 50% in patients with resection of metastases for pulmonary lesions, and up to 33% at 10 years with pulmonary resections.[180][181][182]

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