Clinical utility of the Glasgow Prognostic Score in patients undergoing curative nephrectomy for renal clear cell cancer: basis of new prognostic scoring systems.

BACKGROUND: Measurement of the systemic inflammatory response in malignancy has been recently refined using a selective combination of C-reactive protein and albumin (modified Glasgow Prognostic Score, mGPS). This has prognostic value in patients with metastatic kidney cancer. This study examines the prognostic value of the mGPS in patients undergoing curative nephrectomy for clear cell cancer. METHODS: Patients with localised renal cell carcinoma undergoing potentially curative resection between March 1997 and July 2007 in a single institution were prospectively studied. The mGPS, University of California Los Angeles Integrated Staging System (UISS), 'Stage Size Grade Necrosis' (SSIGN), Kattan and Leibovich scores were constructed. RESULTS: A total of 169 patients were studied. The minimum follow-up was 49 months; the median follow-up of the survivors was 98 months. During this period, 35 patients died of their cancer; a further 24 patients died of intercurrent disease. On univariate survival analysis of the scoring systems, Kattan (P<0.05), UISS (P<0.001), SSIGN (P<0.001) and Leibovich (P<0.001) were significantly associated with cancer-specific survival. Using cancer-specific mortality at 4 years as an endpoint, the area under the receiver operator curve was 0.726 (95% CI 0.629-0.822; P=0.001) for Kattan, 0.776 (95% CI 0.671-0.880; P<0.001) for UISS, 0.812 (95% CI 0.733-0.892; P<0.001) for SSIGN, 0.778 (95% CI 0.666-0.889; P<0.001) for Leibovich and 0.800 (95% CI 0.687-0.912; P<0.001) for the mGPS scoring system. On multivariate analysis of significant independent scoring systems and mGPS, UISS (HR 3.08, 95% CI 1.54-6.19, P=0.002) and mGPS (HR 5.13, 95% CI 2.89-9.11, P<0.001) were significant independent predictors of cancer-specific survival. CONCLUSIONS: The present prospective study shows that the mGPS, an inflammation-based prognostic score, is at least equivalent to and independent of other current validated prognostic scoring systems for patients undergoing curative nephrectomy for renal clear cell cancer. The mGPS is simple, measured preoperatively, based on well-standardised, widely available protein assays, and therefore provides an objective and rational basis before treatment for future staging systems in patients with operable renal cancer.

The longitudinal relationship between circulating concentrations of C-reactive protein, interleukin-6 and interleukin-10 in patients undergoing resection for renal cancer.

The systemic inflammatory response, as evidenced by elevated circulating concentrations of C-reactive protein, is a stage-independent prognostic factor in patients undergoing curative nephrectomy for localised renal cancer. However, it is not clear whether the systemic inflammatory response arises from the tumour per se or as a result of an impaired immune cytokine response. The aim of the present study was to examine C-reactive protein, interleukin-6 and interleukin-10 concentrations before and following curative resection of renal cancer. Sixty-four patients with malignant renal disease and 12 with benign disease, undergoing resection were studied. Preoperatively, a blood sample was collected for routine laboratory analysis with a further sample stored before analysis of interleukin-6 and interleukin-10 using an enzyme-linked immunosorbent assay (ELISA) technique. The blood sampling procedure and analyses were repeated at approximately 3 months following resection. Circulating concentrations of both interleukin-6 and interleukin (P< or =0.01) were higher and a greater proportion were elevated (P<0.05) in malignant compared with benign disease. The renal cancer patients were grouped according to whether they had evidence of a systemic inflammatory response. In the inflammatory group T stage was higher (P<0.01), both interleukin-6 and interleukin-10 concentrations were higher (P<0.001) and elevated (P<0.10) compared with the non-inflammatory group. Tumour volume was weakly correlated with C-reactive protein (r(2)=0.20, P=0.002), interleukin-6 (r(2)=0.20, P=0.002) and interleukin-10 (r(2)=0.24, P=0.001). Following nephrectomy the proportion of patients with elevated C-reactive protein, interleukin-6 and interleukin-10 concentrations did not alter significantly. An elevated preoperative C-reactive protein was associated with increased tumour stage, interleukin-6 and interleukin-10 concentrations. However, resection of the primary tumour did not appear to be associated with significant normalisation of circulating concentrations of C-reactive protein, interleukin-6 or interleukin-10. Therefore, the presence of systemic inflammatory response is unlikely to be solely be determined by the tumour itself, but may be as a result of an impaired immune cytokine response in patients with renal cancer.

The relationship between the preoperative systemic inflammatory response and cancer-specific survival in patients undergoing potentially curative resection for renal clear cell cancer.

The relationship between tumour stage, grade (Fuhrman), performance status (ECOG), a combined score (UCLA Integrated Staging System, UISS), systemic inflammatory response (elevated C-reactive protein concentration), and cancer-specific survival was examined in patients undergoing potentially curative resection for renal clear cell cancer (n=100). On univariate survival analysis, sex (P=0.050), tumour stage (P=0.001), Fuhrman grade (P<0.001), UISS (P<0.001), C-reactive protein (P=0.002) were significant predictors of survival. On multivariate analysis with sex, UISS and C-reactive protein entered as covariates, only UISS (HR 2.70, 95% CI 1.00-7.30, P=0.050) and C-reactive protein (HR 4.00, 95% CI 1.21-13.31, P=0.024) were significant independent predictors of survival. The presence of a preoperative systemic inflammatory response predicts poor cancer-specific survival in patients who have undergone potentially curative resection for renal clear cell cancer.

The systemic inflammatory response, performance status and survival in patients undergoing alpha-interferon treatment for advanced renal cancer.

The prognostic value of C-reactive protein, compared with ECOG performance status (ECOG-ps), in patients receiving alpha-interferon treatment for advanced renal cancer was assessed in 58 patients. In all, 55 patients died on follow-up. On multivariate analysis with ECOG-ps and C-reactive protein entered as covariates, only C-reactive protein was a significant independent predictor of survival (HR 2.03, 95% CI 1.09-3.80, P=0.026).

Partial nephrectomy used to treat renal cell carcinoma arising in a live donor transplant kidney.

There are few reported cases of renal cell carcinoma (RCC) arising in kidney allografts. Whether these tumours occur due to post-transplant malignant transformation or are present at the time of transplantation is unclear. The influence of immunosuppression must be considered in their development, progression and treatment. We report a case of a RCC presenting asymptomatically in a functioning live donor renal allograft 173 months after transplantation. In an attempt to avoid return to dialysis treatment, a partial nephrectomy was carried out. To optimise the procedure, and to assure cancer clearance, combined intraoperative ultrasound and frozen section analysis were used. Our patient remains disease free and dialysis independent at 22 months follow up. To our knowledge, this patient represents the only live donor organ transplant tumour reported to be treated using nephron-sparing surgery and remain dialysis independent. Partial nephrectomy should be considered as a treatment option in such cases.