Surgically treated renal cell carcinoma : prognostic factors and outcomes of treatment

Background Kidney cancer is the 12th most common malignancy worldwide, accounting for over 400,000 new cases in 2018 (1). As renal cell carcinoma (RCC) incidence and mortality, as well as treatment patterns, vary widely in Europe, to plan strategies for the future, we need to comprehend the current situation in Finland. Accurate prognostic tools are essential for detecting cancers amongst the tumours noted in imaging studies and choosing optimal treatment for cancer patients. The Tumor, Node, Metastasis (TNM) staging system and International Society of Urologic Pathology (ISUP)/Fuhrman grading system are the most commonly used prognostic parameters for RCC. Currently, risk stratification relies on prognostic nomograms or risk stratification tools combining clinical, anatomical and histopathological data. However, these models have well-known limitations. Treatment for RCC is changing. Over the last decades, more incidental RCCs were found, and more minor lesions were operated on using less invasive techniques. At the opposite end of the disease spectrum, selected metastatic RCC patients receive a combined treatment consisting of nephrectomy, metastasectomy and oncologic therapies. Surgery for locally advanced and metastasised tumours must be justified by the prospect of an improved outcome or quality of life. Decisions to operate on metastatic RCCs are currently based on expert opinions and nomograms designed for targeted therapy survival estimations only. Thus, better prognostic markers and diagnostic tools are needed. Aims The aims of this PhD study were to evaluate the current changes in the clinical picture, treatment and outcomes of RCC in Helsinki University Hospital district. Further analysis was done to determine the clinical outcomes of surgically treated RCC with tumour thrombus and metastasised RCC (mRCC). The authors aimed to externally validate the performance of the Leuven-Udine (LU) prognostic group model for mRCC and to evaluate the prognostic value of serum concentration of tumour-associated trypsin inhibitor (TATI). The performance of renal tumour diameter and parenchymal invasion depth was compared with more complex classifications to assess their accuracy in predicting the nephrectomy performed. Patients and methods All patients studied were either suspected to have RCC or had RCC, and the majority of patients underwent nephrectomy at the Helsinki University Hospital (HUH). There were 1,719 patients with tumours suspected of RCC evaluated in four periods from 2006 to 2016 for clinical characteristics and treatments offered. From 2006–2014, 142 RCC patients with tumour thrombus (TT) were operated on at HUH. In total, using computed tomography (CT) or magnetic resonance imaging (MRI) images of 915 patients, tumour maximum diameter, depth of invasion, Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score and Renal Tumour Invasion Index (RTII) were estimated. There were 97 patients with metastatic RCC undergoing surgery for metastases. Preoperative and postoperative serum levels of tumour associated trypsin inhibitor (S-TATI) of 132 RCC patients were determined by time-resolved immunofluorescence assay in 2006-2010. Main results and conclusions During the study period, the proportions of frail and co-morbid patients increased significantly as did the percentage of small (diameter ≤4 cm) and asymptomatic tumours. The use of surveillance as treatment increased significantly while the use of cytoreductive nephrectomies (CNs) decreased to 54%. However, CN combined with tyrosine kinase inhibitors remained the primary option in patients with metastatic RCC. However, the changing landscape of RCCs has already affected and will increasingly affect the treatments given. For RCC patients with TT, no statistically significant difference in survival was found amongst the different levels of the venous extension. The prognosis for operated RCC patients with TT was good in the absence of papillary histology of primary tumour, lymphoid or distant metastases. Surgery also remains a feasible option for selected patients in the era of modern oncologic therapy. In predicting the type of nephrectomy, partial or radical, the simple measurements of tumour diameter and parenchymal invasion, were superior to the more complex classification. Hence, all of them were significant predictors for nephrectomy type. Our results recommend that potential anatomical classifications should be tested against these user-friendly measurements, diameter and parenchymal invasion. Overall survival (OS) was more favourable for patients undergoing complete metastasectomy than patients with non-complete metastasectomy and time to systemic therapy was longer. Patients with skeletal metastases had shorter survival than patients with other metastatic sites whereas patients with lung metastases had the most favourable prognosis. In this study population, the performance of the LU prognostic group model could not be validated. Despite the abundant amount of inauspicious prognostic factors in our patient cohort, survival rates were reasonable. Significant associations with preoperative S-TATI and Chronic Kidney Disease Stage (CKD grade), tumour stage, lymph-node involvement, metastatic status and preoperative C-reactive protein (CRP) level were noted. S-TATI, as a continuous variable, however, significantly predicted OS and cancer-specific survival (CSS). Prognostic significance of S-TATI should be further studied in larger patient cohorts and prospective settings.