Cancer-specific mortality in non-metastatic T1a renal cell carcinoma treated with radiotherapy versus partial nephrectomy.

PURPOSE: Radiotherapy (RT) represents a treatment option for small renal masses with proven feasibility and tolerability. However, it has never been directly compared to partial nephrectomy (PN) with cancer-specific mortality (CSM) as an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified T1aN0M0 renal cell carcinoma (RCC) patients treated with RT or PN. We relied on 1:1 propensity score matching (PSM) for age, tumor size and histology. Subsequently, cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied to a subset of patients with tumor size 21-40 mm. RESULTS: Of 40,355 patients with T1aN0M0 RCC, 40,262 underwent PN (99.8%) vs 93 underwent RT (0.2%). RT patients were older (median age 72 vs 60 years, p < 0.001) and harbored larger tumor size (median size 28 vs 25 mm, p < 0.001) and a higher proportion of non-clear cell RCC (49% vs 22%, p < 0.001). After 1:1 PSM (92 RT versus 92 PN patients), cumulative incidence plots' derived CSM was 21.3 vs 4%, respectively. In multivariable CRR models, RT independently predicted higher CSM (hazard ratio (HR) 4.3, p < 0.001). In the subgroup with tumor size 21-40 mm, after 1:1 PSM (72 RT versus 72 PN patients), cumulative incidence plots derived CSM was 21.3% vs 4%, respectively. In multivariable CRR models, RT also independently predicted higher CSM (HR 4.7, p = 0.001). CONCLUSIONS: In T1aN0M0 RCC patients, relative to PN, RT is associated with significantly higher absolute and relative CSM, even in patients with tumor size 21-40 mm.

Stepwise algorithm using computed tomography and magnetic resonance imaging for differential diagnosis of fat-poor angiomyolipoma in small renal masses: A prospective validation study.

OBJECTIVES: To validate the diagnostic accuracy of a stepwise algorithm to differentiate fat-poor angiomyolipoma (fp-AML) from renal cancer in small renal masses (SRMs). METHODS: We prospectively enrolled 223 patients with solid renal masses <4 cm and no visible fat on unenhanced computed tomography (CT). Patients were assessed using an algorithm that utilized the dynamic CT and MRI findings in a stepwise manner. The diagnostic accuracy of the algorithm was evaluated in patients whose histology was confirmed through surgery or biopsy. The clinical course of the patients was further analyzed. RESULTS: The algorithm classified 151 (68%)/42 (19%)/30 (13%) patients into low/intermediate/high AML probability groups, respectively. Pathological diagnosis was made for 183 patients, including 10 (5.5%) with fp-AML. Of these, 135 (74%)/36 (20%)/12 (6.6%) were classified into the low/intermediate/high AML probability groups, and each group included 1 (0.7%)/3 (8.3%)/6 (50%) fp-AMLs, respectively, leading to the area under the curve for predicting AML of 0.889. Surgery was commonly opted in the low and intermediate AML probability groups (84% and 64%, respectively) for initial management, while surveillance was selected in the high AML probability group (63%). During the 56-month follow-up, 36 (82%) of 44 patients initially surveyed, including 13 of 18 (72%), 6 of 7 (86%), and 17 of 19 (89%) in the low/intermediate/high AML probability groups, respectively, continued surveillance without any progression. CONCLUSIONS: This study confirmed the high diagnostic accuracy for differentiating fp-AMLs. These findings may help in the management of patients with SRMs.

Multiphase CT radiomics nomogram for preoperatively predicting the WHO/ISUP nuclear grade of small (< 4 cm) clear cell renal cell carcinoma.

BACKGROUND: Small (< 4 cm) clear cell renal cell carcinoma (ccRCC) is the most common type of small renal cancer and its prognosis is poor. However, conventional radiological characteristics obtained by computed tomography (CT) are not sufficient to predict the nuclear grade of small ccRCC before surgery. METHODS: A total of 113 patients with histologically confirmed ccRCC were randomly assigned to the training set (n = 67) and the testing set (n = 46). The baseline and CT imaging data of the patients were evaluated statistically to develop a clinical model. A radiomics model was created, and the radiomics score (Rad-score) was calculated by extracting radiomics features from the CT images. Then, a clinical radiomics nomogram was developed using multivariate logistic regression analysis by combining the Rad-score and critical clinical characteristics. The receiver operating characteristic (ROC) curve was used to evaluate the discrimination of small ccRCC in both the training and testing sets. RESULTS: The radiomics model was constructed using six features obtained from the CT images. The shape and relative enhancement value of the nephrographic phase (REV of the NP) were found to be independent risk factors in the clinical model. The area under the curve (AUC) values for the training and testing sets for the clinical radiomics nomogram were 0.940 and 0.902, respectively. Decision curve analysis (DCA) revealed that the radiomics nomogram model was a better predictor, with the highest degree of coincidence. CONCLUSION: The CT-based radiomics nomogram has the potential to be a noninvasive and preoperative method for predicting the WHO/ISUP grade of small ccRCC.

Alkaline phosphatase combines with CT factors for differentiating small (≤ 4 cm) fat-poor angiomyolipoma from renal cell carcinoma: a multiple quantitative tool.

PURPOSE: This study aimed to evaluate the diagnostic value of serum and CT factors to establish a convenient diagnostic method for differentiating small (≤ 4 cm) fat-poor angiomyolipoma (AML) from renal cell carcinoma (RCC). MATERIALS AND METHODS: This study analyzed the preoperative serum laboratory data and CT data of 32 fat-poor AML patients and 133 RCC patients. The CT attenuation value of tumor (AVT), relative enhancement ratio (RER), and heterogeneous degree of tumor were detected using region of interest on precontrast phase (PCP) and the corticomedullary phase. Multivariate regression was performed to filter the main factors. The main factors were selected to establish the prediction models. The area under the curve (AUC) was measured to evaluate the diagnostic efficacy. RESULTS: Fat-poor AML was more common found in younger (47.91 ± 2.09 years vs 53.63 ± 1.17 years, P = 0.02) and female (70.68 vs 28.13%, P < 0.001) patients. Alkaline phosphatase (ALP) was higher in RCC patients (81.80 ± 1.75 vs 63.25 ± 2.95 U/L, P < 0.01). For CT factors, fat-poor AML was higher in PCP_AVT (40.30 ± 1.49 vs 32.98 ± 0.69Hu, P < 0.01) but lower in RER (67.17 ± 3.17 vs 84.64 ± 2.73, P < 0.01). Gender, ALP, PCP_AVT and RER was found valuable for the differentiation. When compared with laboratory-based or CT-based diagnostic models, the combination model integrating gender, ALP, PCP_AVT and RER shows the best diagnostic performance (AUC = 0.922). CONCLUSION: ALP was found higher in RCC patients. Female patients with ALP < 70.50U/L, PCP_AVT > 35.97Hu and RER < 82.66 are more likely to be diagnose as fat-poor AML.

Clinical features and Surgical Outcome of Clear Cell Papillary Renal Cell Tumor: result from a prospective cohort.

BACKGROUND: Clear cell papillary renal cell tumor (CCPRCT) was first reported in 2006 a patient with end stage renal disease. After that it was discovered in the kidney without end stage renal disease in the 2010s and started to be mentioned in pathology and urology. The incidence of CCPRCT is low and most of it is discovered incidentally, so there is a lack of reports on clinical characteristics and surgical outcome. METHODS: This study used clinical data from the Seoul National University Prospectively Enrolled Registry for Renal Cell Carcinoma-Nephrectomy (SUPER-RCC-Nx). Between August 2016 and July 2022, patients who underwent radical or partial nephrectomy with clear cell papillary RCC with pathological finding were included in this study. All patients' pathologic reports were reviewed by 1 pathologist. Clinical characteristics and surgical outcomes were presented through descriptive statistics, and Kaplan-Meier curve used for survival analysis. RESULTS: Of the 2057 patients, CCPRCT was reported in 36 patients (1.8%). The median follow up period was 26.8 months. The median age was 67 years, and there were 10 females and 26 males. The median tumor size was 1.2 cm. Twenty-nine patients underwent partial nephrectomy. Seven patients with end-stage renal disease underwent radical nephrectomy. The median operative time for patients who underwent partial nephrectomy was 97.5 min and the estimated blood loss was 100 cc. The median hospital days was 4 and 30-day complications were 2 cases with clavien-dindo classification III or higher. During the follow-up period, there was no recurrence and cancer specific mortality. CONCLUSIONS: The size of CCPRCT was small and there was no advanced stage at that time of diagnosis. There was no recurrence or cancer specific mortality during the follow-up period. A multi-center study with a large scale is needed in the future. TRIAL REGISTRATION: Seoul National University Hospital (SNUH) Institutional Review Board (IRB) (approval number: 2210-126-1371).

Self-reported quality of life as a predictor of mortality in renal cell carcinoma.

BACKGROUND: This study evaluated the utility of self-reported quality of life (QOL) metrics in predicting mortality among all-comers with renal cell carcinoma (RCC) and externally tested the findings in a registry of patients with small renal masses. METHODS: The Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) captured QOL metrics composed of mental component summary (MCS) and physical component summary (PCS) scores. Regression models assessed associations of MCS and PCS with all-cause, RCC-specific, and non-RCC-specific mortality. Harrell's concordance statistic (the C-index) and the Akaike information criterion (AIC) determined predictive accuracy and parsimony, respectively. Findings were tested in the prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry. RESULTS: In SEER-MHOS, 1494 patients had a median age of 73.4 years and a median follow-up time of 5.6 years. Each additional MCS and PCS point reduced the hazard of all-cause mortality by 1.3% (95% CI, 0.981-0.993; P < .001) and 2.3% (95% CI, 0.971-0.984; P < .001), respectively. Models with QOL metrics demonstrated higher predictive accuracy (C-index, 72.3% vs 70.1%) and parsimony (AIC, 9376.5 vs 9454.5) than models without QOL metrics. QOL metrics exerted a greater effect on non-RCC-specific mortality than RCC-specific mortality. External testing in the DISSRM registry confirmed these findings with similar results for all-cause mortality. CONCLUSIONS: Models with self-reported QOL metrics predicted all-cause mortality in patients with RCC with higher accuracy and parsimony than those without QOL metrics. Physical health was a stronger predictor of mortality than mental health. The findings support the incorporation of QOL metrics into prognostic models and patient counseling for RCC.

Protocol for the Flinders Kidney Health Registry: patient outcomes of kidney cancers and nephrectomies.

BACKGROUND: Kidney cancer accounts for 2% of new cancers diagnosed in Australia annually. Partial and radical nephrectomy are the treatment of choice for kidney cancer. Nephrectomy is also performed for living donor kidney transplantation. Nephrectomy is a risk factor for new-onset chronic kidney disease (CKD) or deterioration of pre-existing CKD. Understanding the risk factors for new-onset or deterioration of existing CKD after nephrectomy is important in developing preventive measures to provide better care for these patients. There is also a need to understand the incidence, natural history, management trends, and sequelae of radiofrequency ablation as well as surveillance of small renal cancers or small renal masses (SRMs). Clinical registries are critical in providing excellent patient-centre care and clinical research as well as basic science research. Registries evaluate current practice and guide future practice. The Flinders Kidney Health Registry will provide the key information needed to assess various treatment outcomes of patients with kidney cancer and patients who underwent nephrectomy for other reasons. The registry aims to provide clinical decision makers with longitudinal data on patient outcomes, health systems performance, and the effect of evolving clinical practice. The registry will also provide a platform for large-scale prospective clinical studies and research. METHODS: Patients above the age of 18 undergoing nephrectomy or radiofrequency ablation for any indication and patients with SRMs will be included in the registry. Demographic, clinical and quality of life data will be collected from hospital information systems and directly from the patient and/or caregiver. DISCUSSION: The Registry will report a summary of patient characteristics including indication for treatment, clinical risk profiles, surgical and oncological outcomes, the proportion of patients who progress to CKD and end stage kidney disease, quality of life post treatment as well as other relevant outcomes for all patients who have undergone nephrectomy for any indication, ablation or surveillance for SRMs. The registry will record the follow-up practice after nephrectomy and patient on active surveillance, which will help to develop and enhance a best practice protocol. The collected prospective data will provide a platform for ongoing patient-orientated research and improve patient-centred healthcare delivery.

Urine Molecular Biomarkers for Detection and Follow-Up of Small Renal Masses.

Active surveillance (AS) is the best strategy for small renal masses (SRMs) management; however, reliable methods for early detection and disease aggressiveness prediction are urgently needed. The aim of the present study was to validate DNA methylation biomarkers for non-invasive SRM detection and prognosis. The levels of methylated genes TFAP2B, TAC1, PCDH8, ZNF677, FLRT2, and FBN2 were evaluated in 165 serial urine samples prospectively collected from 39 patients diagnosed with SRM, specifically renal cell carcinoma (RCC), before and during the AS via quantitative methylation-specific polymerase chain reaction. Voided urine samples from 92 asymptomatic volunteers were used as the control. Significantly higher methylated TFAP2B, TAC1, PCDH8, ZNF677, and FLRT2 levels and/or frequencies were detected in SRM patients' urine samples as compared to the control. The highest diagnostic power (AUC = 0.74) was observed for the four biomarkers panel with 92% sensitivity and 52% specificity. Methylated PCDH8 level positively correlated with SRM size at diagnosis, while TFAP2B had the opposite effect and was related to SRM progression. To sum up, SRMs contribute significantly to the amount of methylated DNA detectable in urine, which might be used for very early RCC detection. Moreover, PCDH8 and TFAP2B methylation have the potential to be prognostic biomarkers for SRMs.

Renal tumor biopsy does not increase the risk of surgical complications of minimally invasive partial nephrectomy.

BACKGROUND: For patients with cT1 renal lesions, Partial Nephrectomy (PN) is the gold standard treatment. However, 20% of small renal masses are benign, situation in which the PN is an overtreatment. The percutaneous Renal Tumor Biopsy (RTB) may lower the risk of overtreatment as there is a 90% concordance rate on histotype between the RTB and the final pathology. It has been suggested that the RTB could increase the difficulty of the PN and increase the risk of surgical complications. OBJECTIVE: To compare surgical outcomes and complications of PN with or without previous RTB. DESIGN, SETTING, AND PARTICIPANTS: monocentric retrospective review of patients who underwent laparoscopic or robotic-assisted PN between January 2012 and December 2019. MEASUREMENTS: perioperative complications were recorded using Clavien-Dindo classification, peroperative data included operative time, clamping time and blood loss, and histological outcomes of RTB and PN. RESULTS AND LIMITATIONS: In total, 163 patients were included in our study. There were significantly less benign lesions in PN with prior RTB: 7% (4/56) vs. 20% (22/107) without prior RTB (P=0.03). There were no significant differences regarding Clavien-Dindo>2 perioperative complications with respectively 7% (4/56) vs. 10% (11/107) (P=0.57). Same goes for peroperative data such as duration of surgery (P=0.81), warm ischemia (P=0.07) and blood loss (P=0.13). CONCLUSIONS: RTB does not increase the risk of surgical complications of PN and may reduce the risk of small renal masses overtreatment.

Contrast-enhanced ultrasound (CEUS) imaging for active surveillance of small renal masses.

PURPOSE: To assess the safety and efficacy of contrast-enhanced ultrasound (CEUS) imaging for monitoring small (< 4 cm) renal masses (SRM) in patients undergoing active surveillance (AS). METHODS: We retrospectively selected all consecutive patients with SRMs who underwent AS for at least 6 months at our Institution between January 2014 and December 2018. CEUS imaging was performed by two experienced genitourinary radiologists at established time points. The accuracy of CEUS for monitoring SRM size was compared with that of CT scan. For solid SRMs, four enhancement patterns (EP) were recorded. Radiological progression was defined as SRM growth rate ≥ 5 mm/year. RESULTS: Overall, 158/1049 (15.1%) patients with SRMs underwent AS. At a median follow-up of 25 months (IQR 13-39), no patient died due to renal cell carcinoma (RCC). No patients experienced CEUS-related adverse events. There was a large variability in the pattern of growth of SRMs (overall median growth rate: 0.40 mm/year), with 9.5% of SRMs showing radiological progression. The median SRM size was comparable between CEUS and CT scan examinations at all time points. The vast majority (92.7%) of SRMs did not show a change in their EP over time; and there was no association between the SRM's EP and radiological progression or SRM size. Overall, 43 (27.2%) patients underwent delayed intervention (DI); median SRM size, and median growth rate were significantly higher in these patients as compared to those continuing AS. CONCLUSION: In experienced hands, CEUS is a safe and effective strategy for active monitoring of SRMs in well-selected patients undergoing AS.

Radiomics to better characterize small renal masses.

PURPOSE: Radiomics is a specific field of medical research that uses programmable recognition tools to extract objective information from standard images to combine with clinical data, with the aim of improving diagnostic, prognostic, and predictive accuracy beyond standard visual interpretation. We performed a narrative review of radiomic applications that may support improved characterization of small renal masses (SRM). The main focus of the review was to identify and discuss methods which may accurately differentiate benign from malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat (fat-poor AML) and oncocytoma. Furthermore, prediction of grade, sarcomatoid features, and gene mutations would be of importance in terms of potential clinical utility in prognostic stratification and selecting personalised patient management strategies. METHODS: A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 September 2020 to identify the English literature relevant to radiomics applications in renal tumour assessment. In total, 42 articles were included in the analysis in 3 main categories related to SRM: prediction of benign versus malignant SRM, subtypes, and nuclear grade, and other features of aggressiveness. CONCLUSION: Overall, studies reported the superiority of radiomics over expert radiological assessment, but were mainly of retrospective design and therefore of low-quality evidence. However, it is clear that radiomics is an attractive modality that has the potential to improve the non-invasive diagnostic accuracy of SRM imaging and prediction of its natural behaviour. Further prospective validation studies of radiomics are needed to augment management algorithms of SRM.

Renal Tumor Biopsy: Rationale to Avoid Surgery in Small Renal Masses.

PURPOSE OF REVIEW: The use of renal tumor biopsy (RTB) for small renal masses (SRMs) in daily practice, although safe and accurate, is unusual. Considering the large number of benign tumors in patients with renal masses < 4 cm, some patients with benign tumors are directly referred for surgery instead. This study aimed to report the diagnostic rates of RTB, determine the concordance with surgical pathology, and assess the number of procedures that could have been avoided. We retrospectively studied 255 patients who underwent RTB at our institution in 2010-2019. Of them, 73 were excluded from the analysis (exclusion criteria: > 4 cm, cystic lesion, missing data). The remaining 182 with undetermined SRMs ≤ 4 cm underwent RTB under computed tomography guidance. RECENT FINDINGS: Biopsies were diagnostic in 154/182 (84.6%) cases. Of the non-diagnostic biopsies, 11 were diagnostic when repeated. When RTB was performed of all undetermined SRMs, active treatment (surgery or cryotherapy) was avoided in 50/182 patients (27.5%) because of a benign diagnosis, while 9/182 patients (4.9%) underwent surveillance after a shared multidisciplinary decision. The overall diagnostic rate was 90.6%. All adverse events (approximately 4%) were Clavien-Dindo grade I and did not require active treatment. RTB histology results and nuclear grade were highly concordant with the final pathology (96% and 86.6%, respectively). On univariate logistic regression analysis, male sex was the only contributing factor of diagnostic biopsy. RTB of SRMs should be performed more frequently as part of a multidisciplinary decision-making process since it avoided unnecessary surgical treatment in 1 of 3 patients in our institution.

Diagnostic accuracy of core biopsies of renal masses: Experience in a real-life setting from a tertiary center.

OBJECTIVE: To document and analyze diagnostic accuracy of renal core biopsy (RCB), its diagnostic correlation with resection specimens, and to question the need for immunohistochemistry (IHC) in the preoperative diagnosis of renal masses. MATERIAL AND METHOD: RCBs performed at a reference center between 2007 and 2017 were included. Pathological, clinical, and radiological data were obtained from medical records. RESULTS: Among 302 biopsies included in this study, 274 (90.7%) were diagnostic. Two hundred sixty-six were neoplastic and 179 were of primary renal origin. The most common secondary neoplasms were hematolymphoid (n = 35) and metastatic (n = 17). Sixty-nine tumors were classified as small renal masses (SRMs) (≤4 cm in diameter) and 53 of them were malignant. Nephrectomy was performed in 58 patients. Overall diagnostic accuracy between resections and RCBs was 88.7%. IHC was performed in 160 (53%) cases. In 15 of those, a definite diagnosis could not be rendered. Renal cell origin and subtype were determined by histomorphology alone in 81 and 75 cases, respectively. Sixty primary neoplasms of renal cell origin required IHC for diagnosis. CONCLUSION: RCB is a safe and highly accurate method for the diagnosis of both primary and secondary renal neoplasms. IHC is mostly required for the diagnosis of secondary tumors. Histomorphology is still the primary diagnostic tool, highly dependent on the experience of the surgical pathologist.

Searching for prognostic biomarkers for small renal masses in the urinary proteome.

Renal cell carcinoma (RCC) is frequently diagnosed incidentally as an early-stage small renal mass (SRM; pT1a, ≤4 cm). Overtreatment of patients with benign or clinically indolent SRMs is increasingly common and has resulted in a recent shift in treatment recommendations. There are currently no available biomarkers that can accurately predict clinical behavior. Therefore, we set out to identify early biomarkers of RCC progression. We employed a quantitative label-free liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics approach and targeted parallel-reaction monitoring to identify and validate early, noninvasive urinary biomarkers for RCC-SRMs. In total, we evaluated 115 urine samples, including 33 renal oncocytoma (≤4 cm) cases, 30 progressive and 26 nonprogressive clear cell RCC (ccRCC)-SRM cases, in addition to 26 healthy controls. We identified six proteins, which displayed significantly elevated expression in clear cell RCC-SRMs (ccRCC-SRMs) relative to healthy controls. Proteins C12ORF49 and EHD4 showed significantly elevated expression in ccRCC-SRMs compared to renal oncocytoma (≤4 cm). Additionally, proteins EPS8L2, CHMP2A, PDCD6IP, CNDP2 and CEACAM1 displayed significantly elevated expression in progressive relative to nonprogressive ccRCC-SRMs. A two-protein signature (EPS8L2 and CCT6A) showed significant discriminatory ability (areas under the curve: 0.81, 95% CI: 0.70-0.93) in distinguishing progressive from nonprogressive ccRCC-SRMs. Patients (Stage I-IV) with EPS8L2 and CCT6A mRNA alterations showed significantly shorter overall survival (p = 1.407 × 10-6 ) compared to patients with no alterations. Our in-depth proteomic analysis identified novel biomarkers for early-stage RCC-SRMs. Pretreatment characterization of urinary proteins may provide insight into early RCC progression and could potentially help assign patients to appropriate management strategies.

Guideline adherence for the surgical treatment of T1 renal tumours correlates with hospital volume: an analysis from the British Association of Urological Surgeons Nephrectomy Audit.

OBJECTIVE: To assess European Association of Urology guideline adherence on the surgical management of patients with T1 renal tumours and the effects of centralisation of care. PATIENTS AND METHODS: Retrospective data from all kidney tumours that underwent radical nephrectomy (RN) or partial nephrectomy (PN) in the period 2012-2016 from the British Association of Urological Surgeons Nephrectomy Audit were retrieved and analysed. We assessed total surgical hospital volume (HV; RN and PN performed) per centre, PN rates, complication rates, and completeness of data. Descriptive analyses were performed, and confidence intervals were used to illustrate the association between hospital volume and proportion of PN. Chi- squared and Cochran-Armitage trend tests were used to evaluate differences and trends. RESULTS: In total, 13 045 surgically treated T1 tumours were included in the analyses. Over time, there was an increase in PN use (39.7% in 2012 to 44.9% in 2016). Registration of the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) complexity score was included in March 2016 and documented in 39% of cases. Missing information on postoperative complications appeared constant over the years (8.5-9%).  A clear association was found between annual HV and the proportion of T1 tumours treated with PN rather than RN (from 18.1% in centres performing <25 cases/year [lowest volume] to 61.8% in centres performing ≥100 cases/year [high volume]), which persisted after adjustment for PADUA complexity. Overall and major (Clavien-Dindo grade ≥III) complication rate decreased with increasing HV (from 12.2% and 2.9% in low-volume centres to 10.7% and 2.2% in high-volume centres, respectively), for all patients including those treated with PN. CONCLUSION: Closer guideline adherence was exhibited by higher surgical volume centres. Treatment of T1 tumours using PN increased with increasing HV, and was accompanied by an inverse association of HV with complication rate. These results support the centralisation of kidney cancer specialist cancer surgical services to improve patient outcomes.

Management of the Small Renal Mass: a 2020 Update.

PURPOSE OF REVIEW: Small renal masses (≤ cT1a, less than 4 cm) are a subset of renal tumors with low malignant and metastatic potential but increasing incidence given increased use of cross-sectional imaging. Here, we review the diagnostic and treatment options available for the lesions. RECENT FINDINGS: While the low metastatic potential of SRMs has been known, recent studies show that 30% of SRMs removed surgically are benign. Renal biopsy is a tool that can be implemented to help with diagnosis before treatment (options of which include active surveillance, ablation, and surgery). Active surveillance might be associated with worse cancer-specific survival but all interventional methods appear to fare similarly. Advancements have also been made in percutaneous ablation techniques, and they now are included on multiple guideline statements. Active surveillance, surgery (PN and RN), and thermal ablation are all treatment options for SRMs with similar outcomes but varying side effects.

Are small renal masses all the same?

OBJECTIVES: To evaluate variables that can predict synchronous metastasis in patients presenting with small renal masses. METHODS: We reviewed our institution's prospectively maintained database of 565 patients diagnosed with small renal masses (≤4 cm) over a 16-year period. Variables associated with synchronous metastasis and subsequent relapse were analyzed using χ2 and logistic regression models. RESULTS: A total of 16 patients (2.7%) presented with synchronous metastasis. Just three patients with tumor size <3 cm had metastatic disease at presentation. On multivariate analyses, tumor size >3 cm, symptomatic cancer, age >65 years and ipsilateral synchronous tumors were independent predictors of M1 renal cell carcinoma. A weighted predictive model (concordance index 0.786) showed that a score ≥2 significantly increases the risk of synchronous metastasis (7.9% vs <1% for score <2, P < 0.01, hazard ratio 12.56, 95% confidence interval 5.52-22.85). A total of 498 (90.7%) patients underwent nephrectomies, 27 (4.9%) had ablative therapies and 24 (4.4%) continued on active surveillance/watchful waiting. Over a median follow-up period of 62.8 months, 30 patients (6.1%) had disease recurrence. On multivariate analyses, higher Fuhrman grade and lymphovascular invasion were independent predictors of recurrence. A separate predictive model (concordance index 0.723) showed that either pathological outcome increases recurrence risk up to 15% (P < 0.01, hazard ratio 11.83, 95% confidence interval 5.82-18.76). CONCLUSIONS: Several clinical variables can better identify the metastatic potential of small renal masses. The two proposed predictive models can be valuable tools in future clinical practice.

Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study.

OBJECTIVES: To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry. PATIENTS AND METHODS: Estimated glomerular filtration rate (eGFR) was calculated from creatinine values to determine renal function. QoL was measured using the Short Form 12 (SF-12) questionnaire. The Kaplan-Meier method and Cox proportional hazards regression were used for survival analysis. The mixed-effects model was used for renal function and QoL analysis. RESULTS: Of 638 patients, 231 (36.2%) chose PN, 41 (6.4%) RN, 27 (4.2%) ablation and 339 (53.1%) AS. Cancer-specific survival at 7 years was 98.8% in PN patients and 100% in all other groups. Overall survival (OS) at 7 years was 87.9%, 90.2%, 83.5% and 66.1% in PN, RN, ablation and AS patients, respectively. The OS rate was significantly worse in the AS group than other groups and likely attributable to older age and increased comorbidities. The eGFR was lowest in RN patients but comparable in all other groups. QoL was lowest in AS patients due to lower physical health scores, but mental health scores were similar in all groups. CONCLUSIONS: With excellent oncological outcomes in all groups, nephron-sparing approaches, like PN and ablation, are preferred over RN when intervention is indicated for SRMs. AS is a reasonable option for select patients, given the comparable oncological and mental health outcomes.

Renal tumor biopsy: indicators, technique, safety, accuracy results, and impact on treatment decision management.

CONTEXT: Renal tumor biopsy (RTB), as distinct from the more common renal biopsy for medical renal disease, is an option for patients with renal masses. It is mainly used for small renal masses (SRM) but it may also be indicated for larger masses and even in the presence of metastatic disease. Its main indication in SRM is to avoid intervention for benign kidney tumors but increasingly enables more personalized treatment for kidney cancer patients. OBJECTIVE: The objective of this paper is to provide a comprehensive review of the most recent literature available for RTB including the indications, the technique and also the possible complications. RESULTS: The urological community continues to optimize the indications for RTB. Non-operative treatment modalities, such as active surveillance, ablative modalities, and immunotherapy, may have different results influenced by tumor histology. Continuing concern regarding complications and accuracy and, therefore, the utility of RTB has been addressed. Recent reports support the potential benefit of RTB, safely avoiding a significant number of interventions with good results and minimal complications. CONCLUSION: Urologists should be aware of the benefits of RTB and develop experience with this technique to optimize the results. This diagnostic strategy should be discussed with patients and adopted as it has been with other solid tumors.

Urinary aquaporin 1 and perilipin 2: Can these novel markers accurately characterize small renal masses and help guide patient management?

OBJECTIVE: To evaluate the role of urine aquaporin 1 and perilipin 2 as biomarkers adjunct to renal mass biopsy in guiding the management of patients with small renal masses. METHODS: Preoperative aquaporin 1 and perilipin 2 levels in 57 patients with small renal masses undergoing partial nephrectomy were analyzed and compared with postoperative tumor histology. An algorithm was created utilizing aquaporin 1 and perilipin 2 in conjunction with renal mass biopsy. Cut-off values were implemented to maximize biomarker sensitivity and specificity. Renal mass biopsy utilization and intervention were then compared with rates in traditional renal mass biopsy algorithms. RESULTS: All clear cell and papillary renal cell carcinomas were correctly identified and assigned to the treatment path. All benign lesions were correctly sorted to a confirmatory renal mass biopsy path. Two chromophobe masses did not have elevated aquaporin 1 and perilipin 2, and would require renal mass biopsy. Compared with protocols that call for all small renal masses to be biopsied, confirmatory renal mass biopsy could have been safely avoided in 74% of patients with elevated aquaporin 1 and perilipin 2. Compared with protocols that do not utilize renal mass biopsy, surgical intervention would have been avoided in 23% of patients with benign masses. CONCLUSIONS: Aquaporin 1 and perilipin 2 possess high sensitivity and specificity for detecting clear cell and papillary renal cell carcinoma. Use of these markers might compliment renal mass biopsy in the characterization of small renal masses.