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Objective: To analyse the budget impact of adopting routine renal tumour biopsy (RTB) prior to decision on surgical treatment for clinical T1 renal tumours in Sweden.

Material and methods: This study used data from the National Swedish Kidney Cancer Register including 4,109 T1N0M0 renal tumours surgically treated during the years 2018–2022. We modelled a gradual increase in the proportion of preoperative RTBs over a five-year period, from 15.6 % of surgically removed clinical T1N0M0 renal tumors up to 90 % preoperative RTBs by 2029. Average costs per patient were calculated primarily using the Swedish cost-per-patient database. The analyses were stratified by tumour diameter: ≤40 mm (cT1a) and 41–70 mm (cT1b). The proportion of patients with benign RTB, complication rate and false negative RTBs was estimated from register data and previous research. A healthcare perspective was used and accounted for costs related to biopsy, surgery, follow-up of benign RTBs, complications and re-biopsy in cases of inconclusive RTBs.

Results: For cT1a, increasing preoperative RTBs to 90% of the study population reduced the net annual costs by €691,620, whilst for cT1b, costs increased by €67,630. Overall, an increase in preoperative RTBs to 90% of all patients with cT1 renal tumours was projected to reduce spending by €623,990 annually.

Conclusions: The budget impact analysis of routine preoperative RTBs in suspected renal cell carcinoma indicates net healthcare cost savings in cT1a and potentially for all cT1 tumours.

OBJECTIVE: To assess the safety and diagnostic accuracy of renal tumour biopsy (RTB) in patients with small renal masses (SRM) and to assess if RTB prevents overtreatment in patients with benign SRM.

MATERIAL AND METHODS: In a retrospective, single-centre study from Västmanland, Sweden, 195 adult patients (69 women and 126 men) with SRM ≤ 4 cm who had undergone RTB during 2010-2023 were included. The median age was 70 years (range 23-89). The sensitivity, specificity and predictive values of RTB were calculated using the final diagnosis as the reference standard. Treatment outcomes were recorded for a median 42-month follow-up. Complications following the biopsies were assessed according to the Clavien-Dindo system.

RESULTS: The overall sensitivity of RTB was 95% (95% confidence interval [CI] 90% - 98%) and specificity was 100% (95% CI 95% - 100%). The positive predictive value was 100% and negative predictive value was 92%. The rate of agreement between RTB and the final diagnosis measured using kappa statistics was 0.92. Of the 195 patients, 62 underwent surgery and 48 were treated with ablation. The concordance rate between the RTB histology and final histology after surgery was 89%. Treatment was withheld in 67 of 195 patients with a benign or inconclusive RTB. No patients developed renal cell carcinoma or metastasis during follow-up. Complications occurred in two patients that were classified with Clavien-Dindo grades I and IV.

CONCLUSIONS: Percutaneous renal tumour biopsy appears to be a safe diagnostic method that provides accurate histopathological information about small renal masses and reduces overtreatment of benign SRM.

OBJECTIVE: Several risk factors for end-stage renal disease (ESRD), in patients undergoing surgical treatment for renal cell carcinoma (RCC), have been suggested by others. This study aimed to investigate such risk factors and disclose the effect of developing ESRD, postoperatively, on overall survival. The risk of developing ESRD after RCC diagnosis was also evaluated.

MATERIAL AND METHODS: The data of 16,220 patients with RCC and 162,199 controls were extracted from the Renal Cell Cancer Database Sweden, with linkages across multiple national registers between 2005 and 2020. Cox proportional hazards regression, Kaplan-Meier curves and cumulative incidence were used for statistical analysis.

RESULTS: The 5-year cumulative incidence of ESRD following RCC diagnosis was 2.4% (95% confidence interval [CI] 2.1-2.6) and 0.4% (95% CI 0.3-0.4) for the patients with RCC and controls, respectively. Age, chronic kidney disease, higher T-stage and radical nephrectomy (RN) were significant risk factors for ESRD within 1-year of surgery. A total of 104 and 12,152 patients with and without ESRD, respectively, survived 1-year postoperatively. The 5-year overall survival rates of patients with ESRD and those with RCC only were 50% (95% CI 0.40-0.60) and 80% (95% CI 0.80-0.81), respectively.

CONCLUSIONS: Patients who developed ESRD following renal cancer surgery had significantly poorer survival outcomes. Advanced age, comorbidities, higher-stage tumours and RN were identified as risk factors for developing ESRD. Surgical decisions are crucial. Efforts to spare renal function, including nephron-sparing surgery and active surveillance in appropriate cases, are highly relevant to reduce the development of severe kidney dysfunction.

Objectives: This study aimed to assess the cellular localization and expression levels of hypoxia-inducible factor (HIF) -α proteins (specifically HIF-1α, HIF-2α, and HIF-3α) that play a role in the hypoxia pathway and to determine their correlation with clinicopathological parameters and patient survival in renal cell carcinoma (RCC).

Materials and methods: Tissue microarray (TMA) with cores from 150 clear cell RCCs and 31 non-ccRCC samples. HIF-1α, HIF-2α, and HIF-3α antibodies were used for immunohistochemistry (IHC) of TMA to evaluate the cellular localization and expression levels of HIF-α proteins, specifically in relation to the hypoxia pathway.

Results: The expression levels of the HIF-α proteins were higher in the nucleus than in the cytoplasm. Furthermore, the nuclear expression levels of all HIF-α proteins were significantly higher in clear cell RCC (ccRCC) than in non-ccRCC. Cytoplasmic HIF-3α expression was also higher in ccRCC than in non-ccRCC, whereas cytoplasmic HIF-1α and HIF-2α expression levels were similar between the different RCC types. In ccRCC, nuclear HIF-1α expression levels correlated with both nuclear HIF-2α and HIF-3α levels, whereas cytoplasmic HIF-3α expression levels were associated with HIF-1α only.In non-ccRCC, there was a positive correlation observed between nuclear HIF-1α and HIF-3α expression, but no correlation was found with HIF-2α. In patients with ccRCC, the nuclear expressions of HIF-1α and HIF-3α was significantly associated with cancer-specific survival (CSS) in univariate analysis. This association was no longer evident in multivariate analysis. Notably, there was no correlation observed between nuclear HIF-2α expression and CSS in these patients. In contrast, cytoplasmic expression levels showed no association with CSS.

Conclusion: The expression levels of the three primary HIF-α proteins were found to be higher in the nucleus than in the cytoplasm. Furthermore, the results indicated that HIF-3α and HIF-1α expression levels were significant univariate factors associated with CSS in patients with clear cell RCC. These results highlight the critical role that HIF-3α and HIF-1α play in the hypoxia pathway.

Objective: Renal cell carcinoma (RCC) patients in clinical T1 RCC generally exhibit a favorable prognosis. Guidelines recommend partial nephrectomy (PN), also for cT1b RCCs. Despite a favorable prognosis, there remains risks for upstaging and recurrence for cT1b RCC patients, and the preference for PN has been questionable. Clinical and morphological variables and overall survival (OS) were characterized in a national real-world population.

Methods: Data from the the National Swedish Kidney Cancer Register 2005-2014, with non-metastatic cT1bRCC patients treated surgically and having ≥5 years potential follow-up were included (n = 2006). Patients gender, age, stage, tumor size, RCC type, local and distant tumor recurrence were evaluated.

Results: Among 2006 patients (1219 males, 787 females; mean age 66 years), 1705 underwent radical nephrectomy (RN), and 301 PN. Upstage from cT1b to pathological T3a occurred in 304 (15%) patients. Recurrent disease was diagnosed in 318 (16%) patients, with higher rates in pT3a (25%) compared to pT1b (14%). There was no significant difference in disease recurrences observed between the surgical techniques. Factors associated with increased recurrence risk included age, T-stage, N-stage, and tumor size, while papillary and chromophobe RCCs were associated with decreased risk. Patients with pT3a RCC had a worse 5-year OS rate (67%) compared with pT1b (83%; P < .001, log-rank test). In adjusted analyses, age, tumor size, pT-stage, and pNstage were associated with OS, while treatment with PN was non-inferior compared with RN (hazard ratio 0.91, 95% CI: 0.71-1.45, P = .431).

Conclusion: Patients with clinical T1b RCCs face a non-negligible risk for tumor upstaging, disease recurrence, and decreased OS. The adjusted analyses showed that PN was non-inferior to RN, supporting the recommendation to offer PN.

Background: Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment.

Methods/design: To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis.

Discussion: The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management.

Trial registration: ClinicalTrials.gov NCT03977571 June 6, 2019.

Purpose: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC).

Methods: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005–2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models.

Results: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR.

Conclusion: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.

Risk classification for patients with renal cell carcinoma (RCC) is critical for clinical decision-making and ultimately for patient outcomes [1]. Staging is the single most informative piece of information for risk assessment in patients with cancer. Currently, the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM scheme is the most universally accepted staging system [2]. Since its first publication in 1977, the UICC/AJCC TNM staging system has changed while still retaining its characteristics of simplicity, reproducibility, and user-friendliness.