Diagnostic Biopsy for Small Renal Tumours: A Survey of Current European Practice.

Background and objective: Renal tumour biopsy (RTB) can help in risk stratification of renal tumours with implications for management, but its utilisation varies. Our objective was to report current practice patterns, experiences, and perceptions of RTB and research gaps regarding RTB for small renal masses (SRMs). Methods: Two web-based surveys, one for health care providers (HCPs) and one for patients, were distributed via the European Association of Urology Young Academic Urologist Renal Cancer Working Group and the European Society of Residents in Urology in January 2023. Key findings and limitations: The HCP survey received 210 responses (response rate 51%) and the patient survey 54 responses (response rate 59%). A minority of HCPs offer RTB to >50% of patients (14%), while 48% offer it in <10% of cases. Most HCPs reported that RTB influences (61.5%) or sometimes influences (37.1%) management decisions. Patients were more likely to favour active treatment if RTB showed high-grade cancer and less likely to favour active treatment for benign histology. HCPs identified situations in which they would not favour RTB, such as cystic tumours and challenging anatomic locations. RTB availability (67%) and concerns about delays to treatment (43%) were barriers to offering RTB. Priority research gaps include a trial demonstrating that RTB leads to better clinical outcomes, and better evidence that benign/indolent tumours do not require active treatment. Conclusions and clinical implications: Utilisation of RTB for SRMs in Europe is low, even though both HCPs and patients reported that RTB results can affect disease management. Improving timely access to RTB and generating evidence on outcomes associated with RTB use are priorities for the kidney cancer community. Patient summary: A biopsy of a kidney mass can help patients and doctors make decisions on treatment, but our survey found that many patients in Europe are not offered this option. Better access to biopsy services is needed, as well as more research on what happens to patients after biopsy.

Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

Treatments given to cancer patients can cause negative side effects. For example, a treatment known as androgen deprivation therapy ­ which is used to reduce male sex hormone levels in prostate cancer patients ­ can lead to increased body fat percentage and decreased bone density. These adverse effects can have further negative impacts on patient health, such as increasing the risk of cardiovascular disease and fractures from falls from standing height or less, respectively. Understanding how androgen deprivation therapy contributes to these negative side effects may help clinicians better manage care and outcomes for patients with prostate cancer. Follicle stimulating hormone (or FSH for short) has roles in male and female reproduction but has also been linked to changes in body composition. For example, elevated FSH levels are associated with higher total fat body mass in post-menopausal women. While androgen deprivation therapy is known to alter FSH blood levels, the impact of this change in prostate cancer patients was not well understood. To investigate the effect of androgen deprivation therapy on FSH levels and body composition, Bergamini et al. used X-ray technology to measure total fat body mass in prostate cancer patients before and after undergoing 12 months of androgen deprivation therapy. The findings showed that patient FSH blood levels significantly decreased after 12 months of treatment. Higher FSH blood levels strongly correlated with increased total fat body mass after 12 months of treatment. The findings of this clinical trial suggest that FSH blood levels impact the body composition of patients undergoing androgen deprivation therapy. As a result, FSH blood levels may be a suitable biomarker for identifying patients that are more likely to develop obesity and are therefore at greater risk of complications such as cardiovascular disease.

The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data.

BACKGROUND AND AIM: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. PATIENTS AND METHODS: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. RESULTS: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

Partial nephrectomy for renal tumors: recommendations of the Italian Society of Urology RCC working group.

INTRODUCTION: Partial nephrectomy (PN) aims to remove renal tumors while preserving renal function without affecting oncological and perioperative surgical outcomes. Aim of this paper is to summarize the current evidence on PN and to provide evidence-based recommendations on indications, surgical technique, perioperative management and postoperative surveillance of PN for renal tumors in the Italian clinical and health care system context. EVIDENCE ACQUISITION: This review is the result of an interactive peer-reviewing process of the recent literature on PN for renal tumors carried out by an expert panel composed of members of the Italian Society of Urology (SIU) Renal Cell Carcinoma Working Group. EVIDENCE SYNTHESIS: PN for localized renal tumors is not inferior to radical nephrectomy in terms of survival outcomes while significantly better preserving renal function. Loss of renal function after PN is influenced by medical comorbidities/preoperative renal function and surgical variables such volume of parenchyma preserved and ischemia time. Urologists should select the clamping strategy during PN based on their experience and patient-specific factors. PN can be performed with any surgical approach based on surgeon's expertise and skills. Robotic PN has the potential to expand the minimally invasive indications without interfering with oncological outcomes. The use of 3D virtual models, real time ultrasound and fluorescence tools to assess the anatomy and vascularization of renal tumors during PN may allow a more accurate preoperative planning and intraoperative guidance. Proper postoperative surveillance protocols are essential to detect tumor recurrences and assess functional outcomes. CONCLUSIONS: PN is the standard of care for treatment of localized T1 renal tumors. Recent data supports PN also for selected T2-T3a tumors in experienced institutions. Careful preoperative planning, adequate surgical skills and volumes and appropriate postoperative management and surveillance are paramount to optimize PN oncological and functional outcomes.

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

Artificial Intelligence in Renal Cell Carcinoma Histopathology: Current Applications and Future Perspectives.

Renal cell carcinoma (RCC) is characterized by its diverse histopathological features, which pose possible challenges to accurate diagnosis and prognosis. A comprehensive literature review was conducted to explore recent advancements in the field of artificial intelligence (AI) in RCC pathology. The aim of this paper is to assess whether these advancements hold promise in improving the precision, efficiency, and objectivity of histopathological analysis for RCC, while also reducing costs and interobserver variability and potentially alleviating the labor and time burden experienced by pathologists. The reviewed AI-powered approaches demonstrate effective identification and classification abilities regarding several histopathological features associated with RCC, facilitating accurate diagnosis, grading, and prognosis prediction and enabling precise and reliable assessments. Nevertheless, implementing AI in renal cell carcinoma generates challenges concerning standardization, generalizability, benchmarking performance, and integration of data into clinical workflows. Developing methodologies that enable pathologists to interpret AI decisions accurately is imperative. Moreover, establishing more robust and standardized validation workflows is crucial to instill confidence in AI-powered systems' outcomes. These efforts are vital for advancing current state-of-the-art practices and enhancing patient care in the future.

Single-port robotic partial nephrectomy: impact on perioperative outcomes and hospital stay.

Single-port (SP) robotic surgery is a novel technology and is at the beginning of its adoption curve in urology. The goal of this narrative review is to provide an overview of SP-robotic partial nephrectomy (PN) 4 years after the introduction of the da Vinci SP dedicated platform, focusing on perioperative outcomes, length of stay, and surgical technique. A nonsystematic review of the literature was conducted. The research included the most updated articles that referred to SP robotic PN. Since its commercial release in 2018, several institutions have reproduced robotic PN by using the SP platform, both via a transperitoneal and a retroperitoneal approach. The published SP-robotic PN series are generally based on preliminary experiences by surgeons who had previous experience with conventional multi-arms robotic platforms. The reported outcomes are encouraging. Overall, three studies reported that SP-robotic PN cases had nonsignificantly different operative time, estimated blood loss, overall complications rate, and length of stay compared to the conventional 'multi-arms' robotic PN. However, in all these series, renal masses treated by SP had overall lower complexity. Moreover, two studies underlined decreased postoperative pain as a major pro of adopting the SP system. This should reduce/avoid the need for opioids after surgery. No study compared SP-robotic versus multi-arms robotic PN in cost-effectiveness. Published experience with SP-robotic PN has reported the feasibility and safety of the approach. Preliminary results are encouraging and at least noninferior with respect to those from the multi-arms series. Prospective comparative studies with long-term oncologic and functional results are awaited to draw more definitive conclusions and better establish the more appropriate indications of SP robotics in the field of PN.

Proposal for a Two-Tier Re-classification of Stage IV/M1 domain of Renal Cell Carcinoma into M1 ("Oligometastatic") and M2 ("Polymetastatic") subdomains: Analysis of the Registry for Metastatic Renal Cell Carcinoma (REMARCC).

Purpose: We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC). Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, "Oligometastatic") and M2 (>3, "Polymetastatic"). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current "M" staging. Results: 429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p<0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p<0.001) and 5-year CSS (39% vs. 17%, p<0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500). Conclusion: Subclassification of Stage "M" domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging.

The Association Between Cytoreductive Nephrectomy and Overall Survival in Metastatic Renal Cell Carcinoma with Primary Tumor Size ≤4 cm.

BACKGROUND: It is unknown whether the survival benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) applies to patients with primary tumor size ≤4 cm. OBJECTIVE: To test the association between CN on overall survival (OS) of mRCC patients with primary tumor size ≤4 cm. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology, and End Results (SEER) database (2006-2018), all mRCC patients with primary tumor size ≤4 cm were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity score matching (PSM), Kaplan-Meier plots, multivariable Cox regression analyses, and 6-mo landmark analyses addressed OS according to CN status. Sensitivity analyses examined specific populations of special interest: systemic therapy exposed versus naïve, clear-cell (ccmRCC) versus non-clear-cell (non-ccmRCC) mRCC histology, historical (2006-2012) versus contemporary (2013-2018), and young (≤65 yr) versus old (>65 yr) patients. RESULTS AND LIMITATIONS: Of 814 patients, 387 (48%) underwent CN. After PSM, the median OS was 44 versus 7 mo (Δ = 37 mo; p < 0.001) in CN versus no-CN patients. CN was associated with higher OS in overall population (multivariable hazard ratio [HR]: 0.30; p < 0.001) as well as in landmark analyses (HR: 0.39; p < 0.001). In all sensitivity analyses, CN was independently associated with higher OS: systemic therapy exposed, HR: 0.38; systemic therapy naïve, HR: 0.31; ccmRCC, HR: 0.29; non-ccmRCC, HR: 0.37; historical, HR: 0.31; contemporary, HR: 0.30; young, HR: 0.23; and old, HR: 0.39 (all p < 0.001). CONCLUSIONS: The current study validates the association between CN and higher OS in patients with primary tumor size ≤4 cm. This association is robust, controlled for immortal time bias, and valid across systemic treatment exposure, histologic subtypes, years of surgery, and patient age. PATIENT SUMMARY: In the current study, we tested the association between cytoreductive nephrectomy (CN) and overall survival in patients with metastatic renal cell carcinoma and small primary tumor size. We found a strong association between CN and survival, which persists even after several significant variations in patient and tumor characteristics.

Effect of Degarelix Administration on Bone Health in Prostate Cancer Patients Without Bone Metastases. The Blade Study.

CONTEXT: As patients are now living with prostate cancer for longer, the long-term impact of hormonal treatment on bone health is an increasingly debated subject. OBJECTIVE: To characterize the changes in bone mineral density (BMD) and bone turnover markers after degarelix administration in prostate cancer patients without bone metastases. To explore the predictive role of body composition on treatment induced bone loss. METHODS: BMD and body composition (lean body mass, fat body mass, and appendicular mass index [ALMI]) were assessed by dual X-ray absorptiometry on study entry and after 12 months of degarelix therapy. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) were assessed at baseline, and 6 and 12 months. RESULTS: Twenty-nine patients entered the study. Degarelix administration was associated with a significant decrease in BMD after 12 months (2.4% reduction from baseline at lumbar spine). Serum CTX and ALP increased significantly (median increase from baseline 99% and 19.3%, respectively). An inverse correlation was observed between ALMI and CTX, but not ALP, at both baseline (Pearson r = -0.62, P < .0001) and month 12 (Pearson r = -0.41, P = .032). Moreover, a significant inverse correlation between changes in ALMI and CTX at 12 months (Pearson r = -0.43, P = .019) and a direct relationship between changes of ALMI and ALP (Pearson r = 0.44, P = .016) during degarelix therapy were observed. CONCLUSION: Degarelix administration is associated with a significant decrease in BMD and increase in bone turnover markers. ALMI is a promising predictor of bone loss in prostate cancer patients receiving androgen deprivation therapy, and ALMI changes during therapy are associated with bone turnover derangement favoring bone quality alterations.

Risk of recurrence after nephrectomy: Comparison of predictive ability of validated risk models.

OBJECTIVE: To assess accuracy of University of California Los Angeles Integrated Staging System (UISS), Stage, Size, Grade and Necrosis (SSIGN) score, Leibovich score and GRade, Age, Nodes and Tumor (GRANT) score, the ASSURE (Adjuvant Sunitinib or Sorafenib vs. placebo in resected Unfavorable REnal cell carcinoma) score models and seventh American Joint Committee on Cancer (AJCC)/TNM staging system in predicting recurrence-free survival (RFS) in surgically-treated non-metastatic clear cell renal cell carcinoma (ccRCC) patients. MATERIALS AND METHODS: Kaplan-Meier curves and the log-rank test tested RFS according to risk groups among the UISS, SSIGN, Leibovich and GRANT models and the AJCC/TNM system. The Heagerty's C-index for survival tested for discrimination of each model at different time points after nephrectomy. RESULTS: Three hundred and fifty-eight M0 ccRCC patients were included. RFS significantly differed among each risk category for all models (P < 0.001). SSIGN showed the highest c-index over time (from 0.89 at 6-month to 0.82 at 60-month), followed by Leibovich (from 0.89-0.82), AJCC/TNM stage (from 0.82-0.77), ASSURE (from 0.81 to 0.76), GRANT (from 0.83-0.73) and UISS (from 0.76-0.72). For all models, peak discriminatory ability was reached before 12 months. The most prominent decline occurred within 24 months and reaches the lowest discriminatory ability at 60 months. CONCLUSIONS: Predictive models, with preference for SSIGN and Leibovich scores, are reliable to predict recurrence after nephrectomy and should be recommended to tailor postoperative surveillance protocols.

Prognostic effect of preoperative systemic immune-inflammation index in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma.

BACKGROUND: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of Systemic Immune-Inflammation Index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. METHODS: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut­off value, we found 710 to have the maximum Youden Index value. The overall population was therefore divided into two SII groups using this cut­off (low, <710 vs. high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's Concordance Index (C-Index). The clinical value of the SII was evaluated with decision curve analysis (DCA). RESULTS: Among 613 mRCC patients, 298 (49%) patients had a SII≥710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95% CI: 1.07-1.54, P=0.01) and CSS (HR: 1.29, 95% CI: 1.08-1.55, P=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥710 was associated with OS (HR: 1.25, 95% CI: 1.04-1.50, P=0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.52, P=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index: 0.637 vs. 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII≥710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95% CI: 1.02-1.67, P=0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95% CI: 1.04-1.61, P=0.02) and CSS (HR: 1.31, 95% CI: 1.05-1.63, P=0.02). CONCLUSIONS: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.

Assessment of predictors of renal cell carcinoma progression after nephrectomy at short- and medium-term follow-up and implication on surveillance protocols.

BACKGROUND: Prediction of risk of RCC progression after surgery is important for follow-up planning. We identified predictors of progression-free survival (PFS) and cancer-specific survival (CSS) in a large single institutional cohort and investigated patterns and sites of progression according to stage and grade. METHODS: Node-negative non-metastatic clear-cell RCC (ccRCC) patients treated with radical or partial nephrectomy from 2000 to 2020 were included. Sites of progression were defined as thoracic, abdominal and others (bone/brain). Kaplan-Meier curves and multivariable Cox regression (MCR) models tested for PFS and CSS. RESULTS: Of 384 clear cell RCC N0M0 patients, 301 (78.4%) vs. 83 (21.6%) were pT1-2 vs. pT3-4, respectively; 253 (65.9%) vs. 130 (33.9%) were G1-G2 vs. G3-G4. Thoracic progressions occurred in 2.7% pT1-T2 vs. 21.7% pT3-T4 and 2.8% G1-G2 vs. 14.6% G3-G4 tumors. Abdominal progressions occurred in 4.0% pT1-T2 vs. 13.3% pT3-T4 and 4.3% G1-G2 vs. 9.2% G3-G4. Other progressions occurred in 0.3% pT1-T2 vs. 9.6% pT3-T4 and 0.8% G1-G2 vs. 5.4% G3-G4 (5.4%). Five-year PFS and CSS were 81.7 and 90.6%, respectively. At MCR models, pT3-4 (HR 9.1, P<0.001), G3-G4 (HR 2.7, P=0.003) and PSMs (HR 6.1, P<0.001) independently predicted PFS. Similarly, pT3-4 (HR 10.1, P<0.001), G3-G4 (HR 4.1, P=0.02), and PSMs (HR 5.2, P=0.04) independently predicted CSS. CONCLUSIONS: In ccRCC N0M0 patients, G3-G4, pT3-4, PSMs were independent predictors of progression after surgery. Lower stage and grade ccRCCs progress predominantly in the abdominal sites and may be followed with less frequent extra-abdominal imaging compared to more advanced/aggressive tumors.

Health-related quality of life 24 months after prostate cancer diagnosis: an update from the Pros-IT CNR prospective observational study.

BACKGROUND: This study analyzes patient health-related quality of life (QoL) 24-month after prostate cancer (PCa) diagnosis within the PROState cancer monitoring in ITaly from the National Research Council (Pros-IT CNR) study. METHODS: Pros-IT CNR is an ongoing, longitudinal and observational study, considering a convenience sample of patients enrolled at PCa diagnosis and followed at 6, 12, 24, 36, 48 and 60 months from the diagnosis. Patients were grouped according to the treatment received: nerve sparing radical prostatectomy (NSRP), non-nerve sparing radical prostatectomy (NNSRP), radiotherapy (RT), RT plus androgen deprivation (RT plus ADT) and active surveillance (AS). QoL was measured through the Italian versions of SF-12 and UCLA-PCI questionnaires at diagnosis and at 6-12 and 24-month. The minimal clinically important difference (MCID) was defined as half a standard deviation of the baseline domain. RESULTS: Overall, 1537 patients were included in the study. The decline in urinary function exceeded the MCID at each timepoint only in the NSRP and NNSRP groups (at 24 months -14.7, P<0.001 and -19.7, P<0.001, respectively). The decline in bowel function exceeded the MCID only in the RT (-9.1, P=0.02) and RT plus ADT groups at 12 months (-10.3, P=0.001); after 24 months, most patients seem to recover their bowel complaints. The decline in sexual function exceeded the MCID at each timepoint in the NNSRP, NSRP and RT plus ADT groups (at 6 months -28.7, P<0.001, -37.8, P<0.001, -20.4, P<0.001, respectively). CONCLUSIONS: Although all the treatments were relatively well-tolerated over the 24 month period following PCa diagnosis, each had a different impact on QoL.

Partial nephrectomy in frail patients: Benefits of robot-assisted surgery.

BACKGROUND: To compare the effect of robot-assisted (RAPN) vs. open (OPN) partial nephrectomy on short-term postoperative outcomes and total hospital charges in frail patients with non-metastatic renal cell carcinoma (RCC). METHODS: Within the National Inpatient Sample database we identified 2745 RCC patients treated with either RAPN or OPN between 2008 and 2015, who met the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator criteria. We examined the rates of RAPN vs. OPN over time. Moreover, we compared the effect of RAPN vs. OPN on short-term postoperative outcomes and total hospital charges. Time trends and multivariable logistic, Poisson and linear regression models were applied. RESULTS: Overall, 1109 (40.4%) frail patients were treated with RAPN. Rates of RAPN increased over time, from 16.3% to 54.7% (p < 0.001). Frail RAPN patients exhibited lower rates (all p < 0.001) of overall complications (35.3 vs. 48.3%), major complications (12.4 vs. 20.4%), blood transfusions (8.0 vs. 13.5%), non-home-based discharge (9.6 vs. 15.2%), shorter length of stay (3 vs. 4 days), but higher total hospital charges ($50,060 vs. $45,699). Moreover, RAPN independently predicted (all p < 0.001) lower risk of overall complications (OR: 0.58), major complications (OR: 0.55), blood transfusions (OR: 0.60) and non-home-based discharge (OR: 0.51), as well as shorter LOS (RR: 0.77) but also higher total hospital charges (RR: +$7682), relative to OPN. CONCLUSIONS: In frail patients, RAPN is associated with lower rates of short-term postoperative complications, blood transfusions and non-home-based discharge, as well as with shorter LOS than OPN. However, RAPN use also results in higher total hospital charges.

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma.

BACKGROUND: Accurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. METHODS: mRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA). RESULTS: Among 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16-58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26-1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27-1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23-1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24-1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16-1.99, P=0.002). CONCLUSIONS: In our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.

Changes in body composition and lipid profile in prostate cancer patients without bone metastases given Degarelix treatment: the BLADE prospective cohort study.

BACKGROUND: Luteinizing hormone-releasing hormone (LHRH)-agonists in prostate cancer (PCa) patients induce sarcopenic obesity. The effect of LHRH-antagonist on body composition has never been explored. We evaluated changes in fat (FBM) and lean body mass (LBM) in PCa patients undergoing Degarelix. METHODS: This is a single-center prospective study, enrolling 29 non-metastatic PCa patients eligible to LHRH-antagonist from 2017 to 2019. All patients received monthly subcutaneous injection of Degarelix for 12 months. Changes in FBM and LBM between baseline and 12-month Degarelix, as measured by dual-energy x-ray absorptiometry, were the co-primary endpoints. Secondary endpoints were changes in serum lipids, glucose profile and follicle-stimulating hormone (FSH). Appendicular lean mass index (ALMI) and ALMI/FBM ratio were assessed as post-hoc analyses. Linear mixed models with random intercept tested for estimated least squared means differences (EMD). RESULTS: FBM significantly increased after 12 months (EMD +2920.7, +13.8%, p < 0.001), whereas LBM remained stable (EMD -187.1, -0.3%, p = 0.8). No differences occurred in lipid profile. Glycated hemoglobin significantly increased and serum FSH significantly decreased. A significant inverse relationship was found between serum FSH and ALMI/FBM ratio after 12 month (r = -0.44, p = 0.02). CONCLUSIONS: The BLADE study prospectively evaluated changes in body composition after LHRH-antagonist. LHRH-antagonist therapy is associated to an increased risk of obesity and diabetes, but lean body mass and serum lipids are not affected. This may represent an additional evidence supporting the reduced cardiovascular risk associated with LHRH-antagonist. The role of FSH in influencing sarcopenic obesity in PCa after androgen deprivation deserves to be further explored.

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.