Prognosis of Renal Cell Carcinoma

Renal Cell Carcinomas (RCC) originating from the renal cortex of the kidney comprise approximately 80% to 85% of primary renal neoplasms. The most common primary malignant kidney cancer is Renal Cell Carcinoma (RCC).
Because it is the most common tumor among the renal tumors, the prognosis of Renal Cell Carcinoma (RCC) is a very important subject and draws attention in the medical literature.

Apart from Renal Cell Carcinoma (RCC), other cancers of the kidney include transitional cell carcinomas (%8), parenchymal epithelial tumors such as oncocytoma, collecting tubule tumors, and renal sarcomas. [1]

In pediatric patients, nephroblastoma which also known as Willms Tumor is more common and constitutes approximately 5% to 6% of primary renal tumors. [2]

When Renal Cell Carcinoma (RCC) patients are diagnosed at the early stage or if they have a localized tumor, surgical removal of the mass may provide a cure.

Unfortunately, because of their natural process, most Renal Cell Carcinomas (RCC) has a quiet progression. In many cases, no specific symptoms are seen before the tumor reach the late stages. Therefore, generally, when the diagnosis is made, patients either have late stage renal cancer or have advanced stage tumors. Surgical resection cannot provide a cure in an advanced stage mass. Some patients may even be diagnosed with metastasis. [3]

Above all, recurrence rates are much higher in late stage kidney cancer patients compared to early stage patients even if the tumor is removed by surgical treatment. In conclusion, long-term disease-free survival and prognosis of advanced stage or metastatic Renal Cell Carcinoma (RCC) patients are generally poor. [4]

1. Survival Rates for Renal Cell Carcinoma (RCC)

Mortality rates in the United States due to kidney and renal pelvis cancer decreased by approximately 0.7% between 2006 and 2015. [5]

According to a study published in the literature published by Robson in 1969, the 5-year survival rate of stage I patients was 66%, 64% for stage II patients, 42% for stage III patients and only 11% for stage IV patients. Although a few decades have passed over this study, the five-year survival rates, except stage I, remain almost the same. [6, 7]

The 5-year survival rate of stage I Renal Cell Carcinoma (RCC) patients after radical nephrectomy are about 94%. The 5-year survival rates of Stage II kidney cancer patients are approximately 79%.

Five-Year Survival Rate for Stage 1 Kidney Cancer94%
Five-Year Survival Rate for Stage 2 Kidney Cancer79%
Five-Year Survival Rate for Stage 3 Kidney Cancer42%
Five-Year Survival Rate for Stage 4 Kidney Cancer11%

2. Anatomical Prognostic Factors

Anatomic prognostic factors are determined with such as tumor size, venous invasion, renal capsular invasion, adrenal gland involvement, lymph node involvement, and distant metastasis.

Tumour Node Metastasis (TNM) classification, which is used in almost all cancers today, incorporates these factors and enables all anatomical factors to be evaluated together. [8]

For more information about the staging and Tumour Node Metastasis (TNM) Classifications of Renal Cell Carcinoma, you can read:
Staging and Classification Systems of Renal Cell Carcinoma

3. Histological Prognostic Factors

Histological factors are one of the most important factors in determining prognosis.
These factors include subtype of Renal Cell Carcinoma (RCC), sarcomatoid features, presence, and degree of microvascular invasion, presence and degree of necrosis in the tumor, and involvement of the collecting system. [9]

One of the most widely used and accepted histological factors today is the Fuhrman nuclear grading system. Although this classification system may be affected by intra and inter observer discrepancies, it is a completely independent prognostic factor. [10, 11]

Today, a simplified 2 or 3-layer system, such as the four-tiered staging scheme, which can determine the prognosis accurately, may also be used. [12, 13]

The most recently published World Health Organization / Paris Institute of Statistics (WHO / ISUP) classification system is now become to replace the Fuhrman classification system. However, this new system needs to be validated for prognostic systems and nomograms. [14]

a. Differences between Renal Cell Carcinoma (RCC) subtypes

As a result of a single variable scientific research in the medical literature, chromophobe renal carcinoma (chRCC) patients have a better prognosis than patients with papillary renal carcinoma (pRCC). In the same study, it was also reported that patients with papillary renal carcinoma (pRCC) had a better prognosis than patients with clear cell renal carcinoma (ccRCC). [15, 16]
However, prognostic information obtained according to only to the subtype of Renal Cell Carcinoma (RCC) becomes invalid when the tumor stage is included. For example, the prognosis of a stage 1 clear cell renal carcinoma (ccRCC) may be much better than a stage 4 chromophobe renal carcinoma (chRCC). [17, 16]

For more information about the histopathological subtypes of Renal Cell Carcinoma, you can read:
Histopathology of Renal Cell Carcinoma

A cohort study of 1943 patients comparing clear cell renal carcinoma (ccRCC) to papillary renal carcinoma (pRCC) showed significant survival differences between the two cancers. According to this study, type I papillary cell renal carcinoma (pRCC) has a significantly lower risk of death compared with clear cell renal carcinoma (ccRCC) and type II papillary renal carcinoma (pRCC). [18]

b. Table of histological prognostic factors

Subtype of Renal Cell Carcinoma (RCC)Percantage of Renal Cell Carcinoma (RCC)Advanced disease at diagnosis (T3-4, N+, M+)Fuhrman grade III or IVCancer Specific Survival Rate (CSS) – Hazard Ratio (HR)
Clear Cell Renal Carcinoma (ccRCC)80-90%28%28.5%Referent
Papillary Cell Renal Carcinoma (pRCC)6-15%17.6%28.8%0.64 – 0.85
Chromophobe Renal Cell Carcinoma (chRCC)2-5%16.9%32.7%0.24 – 0.56

Prognosis of Renal Cell Carcinoma (RCC) worsens as the stage and histopathological stage progresses, in all subtypes. The overall survival rate of all Renal Cell Carcinoma (RCC) subtypes is 49%. This rate has improved since 2006, probably, due to the increasing number of incidentally diagnosed cases and the introduction of tyrosine kinase inhibitors (TKI) in treatment. [19, 20]

Sarcomatoid changes can be seen in all Renal Cell Carcinoma (RCC) subtypes, indicating that the tumor has high grade and aggressive cells.

c. Prognosis of Renal Cell Carcinoma (RCC) by stage and histopathological grade

GradeHazard Ratio (HR)
[%95 confidental interval]
T2N0M02.71 (2.17-3.39)
T3N0M05.20 (4.36-6.21)
T4N0M016.88 (12.40-22.98)
N+M016.33 (12.89-20.73)
M+33.23 (28.18-39.18)
Grade 1Referent
Grade 21.16 (0.94-1.42)
Grade 31.97 (1.60-2.43)
Grade 42.82 (2.08-3.31)

d. Survival of patients treated by radical nephrectomy or partial radical nephrectomy

Long term survivals of sporadically clear cell (ccRCC), papillary cell (pRCC) and chromophobe cell (chRCC) renal cell carcinomas after surgical resection were reported in a cohort study between 1997 and 2003, as the table below. [21]

Survival Time5 years (%)10 years (%)15 years (%)20 years (%)
Clear Cell Renal Carcinoma (ccRCC)71 (69-73)62 (60-64)56 (53-58)52 (49-55)
Papillary Cell Renal Carcinoma (pRCC)91 (88-94)86 (82-89)85 (81-89)83 (78-88)
Chromophobe Renal Cell Carcinoma (chRCC)88 (83-94)86 (80-92)84 (77-91)81 (72-90)

In addition, prognostic factors have been identified between the two subtypes of papillary cell carcinoma. Accordingly, type I has a better prognosis and type II papillary cell carcinomas generally have higher degrees and have higher metastasis potentials. [22]

In addition, renal cancers with xp11.2 translocation have an extremely poor prognosis. Although these cancers are rare, the possibility of tumor formation, especially in young patients, should be kept in mind. [23]

4. Clinical Prognostic Factors

The factors listed below are used to determine the prognosis of Renal Cell Carcinomas (RCC) clinically. [24, 25]

  • Status of performance
  • Local symptoms
  • C-reactive protein levels (CRP)
  • Albumin levels
  • Platelet count
  • Ratio of neutrophil-lymphocyte
  • Cachexia
  • Anemia

5. Molecular Prognostic Factors

Factors such as carbonic anhydrase IX (CaIX), VEGF, hypoxia-inducible factor (HIF), Ki67 (proliferation), p53, p21 [26], PTEN (phosphatase and tensin homolog) cell cycle, E-cadherin, osteopontin [27] CD44 (cell) adhesions) [28, 29], CXCR4 [30], are currently being used to determine the prognosis of Renal Cell Carcinoma (RCC), and more of them are under investigation [31, 32]

None of these markers has yet to be proven to improve the predictive accuracy of currently used prognostic systems and nomograms. Today, their use in clinical practice is not recommended.

Several retrospective types of research and large molecular screening programs on clear cell renal carcinoma (ccRCC) have identified mutations and genes associated with this cancer.
The most important of these is that the regions where the expression of the BAP1 and PBRM1 genes occurred in chromosome 3p, are deleted in more than 90% of cases. According to these published scientific studies, the prognosis of patients with BAP1 mutant tumors is reported to be worse than patients with PBRM1 mutant tumors.
It has also been shown that these mutations are independent prognostic factors in the recurrence of the tumor. [33, 34, 35]

Relapse rates can be estimated by using sixteen gene signatures with the validated data from surgical series. This signature is highly likely to be adopted in clinical trials and may help practitioners in the clinic over time. [36]

Interest in the potential contribution of immunotherapy in the treatment of Renal Cell Carcinoma (RCC) is increasing. Prognostic information of the blockade of immunosuppressive molecules such as PD-L1 and cytokines are promising in terms of therapeutic outcomes.

Genome-Wide Association Studies, miRNA, SNPs and chromosomal alterations and gene methylations can contribute to both prognostic and diagnostic information.

Today, there are many studies in the medical literature showing that the gain of 7q, 8q and 20q chromosomal regions and loss of 9p, 9q, and 14q chromosome regions are associated with a poor prognosis.

In addition, CpG-methylation-based assays can independently predict the survival rate of clear cell renal carcinomas (ccRCC). [37, 38]

6. Table of Prognostic Systems and Nomograms

Many postoperative prognostic systems which combine the many independent prognostic factors have been developed and externally validated. [39, 40]

These prognostic systems can better predict survival than the Tumour Node Metastasis (TNM) classification or the Fuhrman classification alone.

The major advantage of the prognostic systems and nomograms is that they measure predictive accuracy by providing an objective assessment of all new predictive parameters.

All new prognostic parameters or systems must prove that their predictive accuracy is better than conventional postoperative prognosis schemes before they are adopted. [41]

Recent studies have identified several new preoperative nomograms with excellent predictive accuracy. [42, 43]


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