Improved prediction of High ISUP Grade Clear Cell Renal Cell Carcinoma

Renal cell carcinoma (RCC) is one of the most common malignancies of the genitourinary system, and it constitutes 3% of adult malignant tumors and accounts for 2% of all cancer mortality. Clear cell RCC (ccRCC) is the predominant histological subtype of RCC, accounting for approximately 80% of cases.

Advanced ccRCCs are thought to be associated with a more aggressive clinical course and worse prognosis. The Fuhrman system was initially recommended as the histological grading system for RCC, but despite its wide use, it failed to take into consideration the latest histological subtypes of RCC, and was prone to poor interpretability and consequently poor inter-observer concordance regarding histopathological scoring. Therefore, the International Society of Urological Pathology (ISUP) Consensus Conference made recommendations, in an attempt to improve the prognostic value of these factors in the assessment of the various histomorphological phenotypes of RCC, by applying these recommendations, increased tumor grade was found to be associated with poor patient outcomes. Thus, the International Agency for Research on Cancer replaced the Fuhrman system with a new system based on the WHO/ISUP grading system.

Renal tumor biopsy plays an important role in the screening of candidates for personalized therapy and yet the sensitivity and accuracy of renal tumor biopsy analysis remains questionable, particularly for ccRCC, therefore the accuracy of diagnosis from renal tumor biopsy remains inadequate. Given the diagnostic inadequacies associated with preoperative biopsy in ccRCC, an increasing number of studies have attempted to incorporate more convenient clinical profiles and immunohistochemical or gene expression biomarkers to refine the ISUP grading system.

In a recent research paper published in journal, Frontiers in Oncology, Fudan University Shanghai Cancer Center led by Professor Ding-Wei Ye decided to investigate the value of integrating clinical profiles and immunohistochemical biomarkers in facilitating the diagnosis of high ISUP grade ccRCC. A total of 362 patients undergoing radical nephrectomy or nephron-sparing surgery in their institute were recruited for the study. The analysis obtained was used to construct a nomogram for the prediction of ISUP grade risk in ccRCC.

Their study consisted of two stages; the first stage involved an assessment of the associations between specific clinical or immunohistochemical markers and ISUP while the second stage consisted of a prognostic model comprising combined profiles was constructed and verified to predict high-grade risk using nomogram.

The authors observed when classifying the patients that patients with high ISUP grade were more likely to be older, have a larger maximal tumor diameter, be symptomatic, and to have undergone radical nephrectomy. Also it was observed that seven indicators were identified for predicting grade, these are age, tumor diameter, surgical method, CK7, Ki-67, PTEN, and mTOR expression.

Furthermore, the validation of the integrated score and nomogram in predicting high ISUP was achieved through studies in 121 ccRCC patients with fully recorded pre-operation surgical plans; it was observed that the AUC index was 0.791 which was similar to that of the training set. This confirms that the integrated score and nomogram demonstrate good performance in predicting ISUP grade.

Professor Ding-Wei Ye and his colleagues successfully developed an integrated nomogram comprising clinical and immunohistochemical indicators to predict high ISUP grade for ccRCC patients. This nomogram offers potentially useful information during preoperative risk assessment and may help urologists when evaluating personalized management regimens.