Latest News on Renal Cell Carcinoma : Nov 2020

Prognostic significance of morphologic parameters in renal cell carcinoma

The prognostic significance of morphologic parameters was evaluated in 103 patients with renal cell carcinoma diagnosed during 1961–1974. Pathologic material was classified as to pathologic stage, tumor size, cell arrangement, cell type and nuclear grade. Four nuclear grades (1–4) were defined in order of increasing nuclear size, irregularity and nucleolar prominence. Nuclear grade was more effective than each of the other parameters in predicting development of distant metastasis following nephrectomy. Among 45 patients who presented in Stage I, tumors classified as nuclear grade I did not metastasize for at least 5 years, whereas 50% of the higher grade tumors did so. Moreover, among Stage I tumors there was a significant difference in subsequent metastatic rate between nuclear grade 1 and 2. There was an apparent positive relationship between cell type and metastatic rate; clear cell tumors were less aggressive than predominantly granular cell tumors (metastatic rate 38% versus 71%). This relationship is in part a function of the nuclear grade: only 5% of grade 3 and 4 tumors consisted of clear cells, whereas such high grades were seen in 57% of granular cell tumors. The size of the primary correlated well with the stage at the time of surgery. However, with the exception of extremely large and small tumors, the size was not useful in predicting the subsequent course of patients treated for Stage I tumors. Nuclear grade was the most significant prognostic criterion for the outcome of State I renal cell carcinoma. [1]

Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

BACKGROUND

Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment.

METHODS

A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety.

RESULTS

The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%).

CONCLUSIONS

Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. [2]

Comprehensive molecular characterization of clear cell renal cell carcinoma

Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment. [3]

Gastric Metastatis of Renal Cell Carcinoma Presenting as Polyps

Metastatic tumors of the stomach are very rare, with an incidence of 0, 2%- 0, 7% in the autopsy series. Malignant melanoma, carcinomas of breast, esophagus and lung are the most frequent primary tumor sites. The present case describes a 57-year-old woman who presented to the gastroenterology department with epigastric pain, nausea and vomiting for two months. Examinations revealed gastric metastasis of Renal Cell Carcinoma. [4]

Squamous Cell Carcinoma of the Kidney and Renal Pelvis: A Review of the Literature

Background: Primary squamous cell carcinoma of renal pelvis/kidney (PSCCRP/K) is rare with controversies regarding its histogenesis.

Aim: To review the literature.

Methods: Various internet data bases were searched.

Literature Review: Few cases of PSCCRP/K have been reported with only three cases of PSCC of the renal parenchyma without involvement of renal pelvis. Some PSCCRP/Ks have been associated with renal calculi, chronic infections, vesicoureteric reflux. Some cases had developed many years after successful percutaneous nephrolithotomy; a case was reported many years after curative radiotherapy for testicular tumour. The tumours are initially diagnosed in advanced stages; generally the prognosis has been poor following nephrectomy/nephrouretectomy. Conventional radiological features of the disease are non-specific and cannot differentiate the lesion from other tumours or xanthogranulomatous pyelonephritis. Diagnosis is based upon strict histopathological criteria of the microscopic characteristics of the tumour. Primary tumour elsewhere should be excluded with radiological images. PSCCRP/K should be suspected when a renal/renal pelvis mass is found with a history of chronic or past stone disease treatment. Perhaps if patients who have undergone treatment for kidney stones are carefully followed-up with radiological imaging, (for example, ultra-sound-scans and/or MRI and when eventually required a CT scan properly indicated and
performed) for a long time, PSCCR/Ks may be diagnosed at an early stage of the disease in order to provide early curative treatment.

Conclusions: PSCCRP/Ks have been reported sporadically and a number of them have been associated with renal calculi and chronic infections of the urinary tract. These malignancies on the whole are initially diagnosed in advanced stages and hence associated with poor prognosis. Histopathological examination of the lesion so far is the definite way to confirm the diagnosis. PSCCRP/K should be considered a differential diagnosis when a patient is found to have a renal / renal pelvis mass and a history of treatment for renal pelvis calculi, or chronic inflammations. [5]

Reference

[1] Fuhrman, S.A., Lasky, L.C. and Limas, C., 1982. Prognostic significance of morphologic parameters in renal cell carcinoma. The American journal of surgical pathology, 6(7), pp.655-664.

[2] Motzer, R.J., Escudier, B., McDermott, D.F., George, S., Hammers, H.J., Srinivas, S., Tykodi, S.S., Sosman, J.A., Procopio, G., Plimack, E.R. and Castellano, D., 2015. Nivolumab versus everolimus in advanced renal-cell carcinoma. New England Journal of Medicine, 373(19), pp.1803-1813.

[3] Cancer Genome Atlas Research Network, 2013. Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 499(7456), pp.43-49.

[4] Unler, G., Ozgur, G., Gokturk, H., Erinanc, O. and Kal, O. (2015) “Gastric Metastatis of Renal Cell Carcinoma Presenting as Polyps”, Journal of Advances in Medicine and Medical Research, 11(8), pp. 1-5. doi: 10.9734/BJMMR/2016/20203.

[5] Kodzo-Grey Venyo, A. (2015) “Squamous Cell Carcinoma of the Kidney and Renal Pelvis: A Review of the Literature”, Journal of Cancer and Tumor International, 2(4), pp. 155-181. doi: 10.9734/JCTI/2015/19631.

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