Does the Timing of Cytoreductive Nephrectomy Impact Outcomes? Analysis of REMARCC Registry Data for Patients Receiving Tyrosine Kinase Inhibitor Versus Immune Checkpoint Inhibitor Therapy.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p < 0.001) and CSS (83% vs 30%; p < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN (p < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p = 0.042) and CSS (90% vs 30%, p = 0.019) for delayed CN after IO therapy, but not after TKI therapy. Conclusions and clinical implications: For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC. Patient summary: For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery.

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.

Personalised indocyanine-guided lymphadenectomy for prostate cancer: a randomised clinical trial.

OBJECTIVES: To study the safety and efficacy of a personalised indocyanine-guided pelvic lymph node dissection (PLND) against extended PLND (ePLND) during radical prostatectomy (RP). PATIENTS AND METHODS: Patients who were candidates for RP and lymphadenectomy, with intermediate- or high-risk prostate cancer (PCa) according to the National Comprehensive Cancer Network guidelines, were enrolled in this randomised clinical trial. Randomisation was made 1:1 to indocyanine green (ICG)-PLND (only ICG-stained LNs) or ePLND (obturator fossa, external, internal, and common iliac and presacral LNs). The primary endpoint was the complication rate within 3 months after RP. Secondary endpoints included: rate of major complications (Clavien-Dindo Grade III-IV), time to drainage removal, length of stay, percentage of patients classified as pN1, number of LNs removed, number of metastatic LNs, rate of patients with undetectable prostate-specific antigen (PSA), biochemical recurrence (BCR)-free survival, and rate of patients with androgen-deprivation therapy at 24 months. RESULTS: A total of 108 patients were included with a median follow-up of 16 months. In all, 54 were randomised to ICG-PLND and 54 to ePLND. The postoperative complication rate was higher in the ePLND (70%) vs the ICG-PLND group (32%) (P < 0.001). Differences between major complications in both groups were not statically significant (P = 0.7). The pN1 detection rate was higher in the ICG-PLND group (28%) vs the ePLND group (22%); however, this difference was not statistically significant (P = 0.7). The rate of undetectable PSA at 12 months was 83% in the ICG-PLND vs 76% in the ePLND group, which was not statistically significant. Additionally, there were no statistically significant differences in BCR-free survival between groups at the end of the analysis. CONCLUSIONS: Personalised ICG-guided PLND is a promising technique to stage patients with intermediate- and high-risk PCa properly. It has shown a lower complication rate than ePLND with similar oncological outcomes at short-term follow-up.

Effect of smoking, hypertension and lifestyle factors on kidney cancer - perspectives for prevention and screening programmes.

Renal cell carcinoma (RCC) incidence has doubled over the past few decades. However, death rates have remained stable as the number of incidental renal mass diagnoses peaked. RCC has been recognized as a European health care issue, but to date, no screening programmes have been introduced. Well-known modifiable risk factors for RCC are smoking, obesity and hypertension. A direct association between cigarette consumption and increased RCC incidence and RCC-related death has been reported, but the underlying mechanistic pathways for this association are still unclear. Obesity is associated with an increased risk of RCC, but interestingly, improved survival outcomes have been reported in obese patients, a phenomenon known as the obesity paradox. Data on the association between other modifiable risk factors such as diet, dyslipidaemia and physical activity with RCC incidence are conflicting, and potential mechanisms underlying these associations remain to be elucidated.

Radical cystectomy and orthotopic neobladder in a patient with a preexisting three-components inflatable penile prosthesis.

INTRODUCTION AND OBJECTIVES: As erectile dysfunction is more commonly being diagnosed and treated with a preexisting inflatable penile prosthesis (IPP) insertion at younger ages, surgeons will increasingly encounter pre-placed abdominal reservoirs when performing pelvic surgery. MATERIALS AND METHODS: A 69-year-old Caucasian man with BCG refractory carcinoma-in-situ (CIS) and past history of non-invasive high-grade urothelial carcinoma of the bladder was a candidate for a radical cystectomy and an ileal-neobladder diversion. He had a three-components IPP inserted for the treatment of Peyronie disease and organic erectile dysfunction (ED). During the radical cystectomy the reservoir was encapsulated on the left lateral pelvic wall over the external iliac vessels. It was isolated and IPP was inflated to reduce the reservoir size. After accurate disinfection, the reservoir was removed from Retzius space without disconnecting it from the pump. Then, the radical cystectomy was carried out without any intraoperative complications and Studer ileal orthotopic neobladder was performed. At the end of the surgery, the reservoir was disinfected with the Mulcahy protocol and then placed in the same position. RESULTS: A week after catheter removal the IPP was successfully activated. The patient's postoperative recovery was uneventful and no postoperative complication occurred. Definitive histological examination described a multifocal urothelial carcinoma of the bladder: pG3Tis N0 R0. The patient reports excellent functionality of the penile prosthesis and is currently using it. CONCLUSIONS: Sexual functionality preservation in oncologic patients should be pursued when possible. In this report, the functionality of the IPP was preserved, while still performing oncologically radical procedures. A multicenter study is needed to assure more solid recommendations on this rare procedure that is surely burdened by a lot of risks.

Penile prosthesis impending erosion: Surgical technique for extracapsular re-implantation reconstruction.

INTRODUCTION AND OBJECTIVES: Impending erosion is an unusual complication of inflatable penile prosthesis that can strongly impact on patient's morbidity and quality of life. In this case report we present a salvage surgery technique for impending erosion performed in a 57-year-old man. MATERIALS AND METHODS: We present our surgical technique for cylinder reimplantation in an impending erosion of a three-component inflatable prosthesis with a peno-scrotal access and extracapsular reseating of the cylinder. RESULTS: No post-operative complication occurred, and the patient regained full function of the prosthesis after recovery. The surgical site healed well with no signs of infections. CONCLUSIONS: Impending erosion is a problematic complication of penile prosthesis; however, can be administered with a salvage technique avoiding the explant of the IPP.

Assessing Trifecta Achievement after Percutaneous Cryoablation of Small Renal Masses: Results from a Multi-Institutional Collaboration.

Background and Objectives: To assess efficacy and safety of Percutaneous Cryoablation (PCA) of small renal masses (SRMs) using Trifecta outcomes in a large cohort of patients who were not eligible for surgery. Materials and methods: All PCAs performed in four different centers between September 2009 and September 2019 were retrospectively evaluated. Patients were divided in two different groups depending on masses dimensional criteria: Group-A: diameter ≤ 25 mm and Group-B: diameter > 25 mm. Complications rates were reported and classified according to the Clavien−Dindo system. The estimate glomerular filtration rate (eGFR) was calculated before PCA and during follow-up schedule. Every patient received a Contrast Enhanced Ultrasound (CEUS) evaluation on the first postoperative day. Radiological follow-up was taken at 3, 6, and 12 months for the first year, then yearly. Radiological recurrence was defined as a contrast enhancement persistence and was reported in the study. Finally, Trifecta outcome, which included complications, RFS, and preservation of eGFR class, was calculated for every procedure at a median follow-up of 32 months. Results: The median age of the patients was 74 years. Group-A included 200 procedures while Group-B included 140. Seventy-eight patients were eligible for Trifecta evaluation. Trifecta was achieved in 69.6% of procedures in Group-A, 40.6% in Group-B (p = 0.02). We observed an increased rate of complication in Group-B (13.0% vs. 28.6; p < 0.001). However, 97.5% were

External validation of the VENUSS prognostic model to predict recurrence after surgery in non-metastatic papillary renal cell carcinoma: A multi-institutional analysis.

OBJECTIVE: Recently, VENUSS (VEnous extension, NUclear Grade, Size, Stage), as a prognostic model, was defined to predict disease recurrence (DR) after curative surgery of non-metastatic papillary renal cell carcinoma (papRCC). This study aimed to validate the VENUSS prognostic model in a large multi-institutional European cohort of patients with histopathologically proven papRCC after curative surgery for non-metastatic disease. PATIENTS AND METHODS: Overall, 980 patients undergoing partial or radical nephrectomy for sporadic, unilateral and non-metastatic papRCC between 1987 and 2020 were included from 7 European tertiary institutions. The primary outcome was the prediction of DR by VENUSS score and VENUSS risk groups. Chi-square, Kruskal-Wallis, Cox-regression and Kaplan-Meier survival analyses were used in statistical methods. The Concordance (C) Index was calculated to assess model's discriminatory power. RESULTS: The median age was 64 (IQR:55-70) years and 82.6 % (n = 809) of patients were male. Median VENUSS score was 2 (IQR: 0-4), and 62.9 % (n = 617), 23.9 % (n = 234) and 13.2 % (n = 129) of patients was classified into low, intermediate and high risk according to the VENUSS model, respectively. At a median follow-up of 48 (IQR:23-88) months, the disease recurred in 6.6%, 18.8% and 63.8%, and the 5-year recurrence-free survival was 93.8%, 80.7% and 26.7% in low, intermediate and high-risk groups, respectively. (P < 0.001) Each increase in VENUSS score had 1.52-fold (95%CI:1.45-1.60, P < 0.001) DR risk. Compared with the VENUSS low risk, the intermediate risk had a 2.91-fold increased DR risk (95%CI:1.90-4.46, P < 0.001) and 17.9-fold (95%CI:12.25-26.25, P < 0.001) in high risk, while it was 6.07-fold greater in high risk vs. intermediate risk (95%CI:4.17-8.83, P < 0.001). The discrimination was 81.2% (95%CI:77.5%-84.8%) for the VENUSS score, and 78.6% (95%CI:74.8%-82.4%) for VENUSS risk groups, respectively. Both the VENUSS score and groups were well calibrated. CONCLUSIONS: This contemporary multi-institutional European large dataset validated the use of VENUSS score and VENUSS risk groups on the prediction of DR after curative surgery in patients with non-metastatic papRCC. The VENUSS prognostic model can provide valuable information for patient counselling, follow-up and patient selection for adjuvant trials.

The role of angioembolization in the management of blunt renal injuries: a systematic review.

BACKGROUND: Recently, renal angioembolization (RAE) has gained an important role in the non-operative management (NOM) of moderate to high-grade blunt renal injuries (BRI), but its use remains heterogeneous. The aim of this review is to examine the current literature on indications and outcomes of angioembolization in BRI. METHODS: We conducted a search of MEDLINE, EMBASE, SCOPUS and Web of Science Databases up to February 2021 in accordance with PRISMA guidelines for studies on BRI treated with RAE. The methodological quality of eligible studies and their risk of bias was assessed using the Newcastle-Ottawa scale RESULTS: A total of 16 articles that investigated angioembolization of blunt renal injury were included in the study. Overall, 412 patients were included: 8 presented with grade II renal trauma (2%), 97 with grade III renal trauma (23%); 225 with grade IV (55%); and 82 with grade V (20%). RAE was successful in 92% of grade III-IV (294/322) and 76% of grade V (63/82). Regarding haemodynamic status, success rate was achieved in 90% (312/346) of stable patients, but only in 63% (42/66) of unstable patients. The most common indication for RAE was active contrast extravasation in hemodynamic stable patients with grade III or IV BRI. CONCLUSIONS: This is the first review assessing outcomes and indication of angioembolization in blunt renal injuries. The results suggest that outcomes are excellent in hemodynamic stable, moderate to high-grade renal trauma.

Percutaneous cryoablation for high-complexity renal masses: complications, functional and oncological outcomes.

BACKGROUND: During the past two decades cryoablation (CA) has become a therapeutic option for the management of localized cT1 renal masses in comorbid patients. We analyzed the mid-term functional and oncological outcomes of CA in the treatment of cT1 renal masses which were classified as high-complexity masses according to the PADUA system. METHODS: A total of 299 patients underwent percutaneous CA between November 2007 and December 2018 in 4 institutions for cT1N0M0 renal masses. All patients with high-complexity (PADUA≥10) renal tumors were included. Technical failure of CA was considered an exclusion criterion. RESULTS: Inclusion criteria were met by 45 patients. Median Charlson Comorbidity Index (CCI) was 6.0 (IQR: 5.0-7.0), median age was 74 years (IQR: 64.5-79.5). Seven Clavien 1 and 1 Clavien 2 procedure-related complications were reported. Median eGFR at baseline was 64.3mL/min (IQR: 52.0-82.3) while at the 1-year follow-up was 61.4 mL/min (IQR: 44.0-74.5). The median follow-up was 32 months (IQR: 13.25-47.5). Local recurrences were detected in 6 patients; 3 of them underwent re-cryoablation while the others started active surveillance. Median time to recurrence was 17.5 months (IQR: 7.8-27.3). Cancer-specific survival and metastasis-free survival were 100%, while overall survival was 86.7%. CONCLUSIONS: CA proved to be a valuable therapeutic option for the management of patients with cT1 high-complexity PADUA≥10 renal tumors as it provides a low rate of procedural morbidity and good preservation of renal function. However, these results are counterbalanced by a recurrence rate that appears to be higher than those reported on surgically treated patients.

Available active surveillance follow-up protocols for small renal mass: a systematic review.

PURPOSE: To evaluate follow-up strategies for active surveillance of renal masses and to assess contemporary data. METHODS: We performed a comprehensive search of electronic databases (Embase, Medline, and Cochrane). A systematic review of the follow-up protocols was carried out. A total of 20 studies were included. RESULT: Our analysis highlights that most of the series used different protocols of follow-up without consistent differences in the outcomes. Most common protocol consisted in imaging and clinical evaluation at 3, 6, and 12 months and yearly thereafter. Median length of follow-up was 42 months (range 1-137). Mean age was 74 years (range 67-83). Of 2243 patients 223 (10%) died during the follow-up and 19 patients died of kidney cancer (0.8%). The growth rate was the most used parameter to evaluate disease progression eventually triggering delayed intervention. Maximal axial diameter was the most common method to evaluate growth rate. CT scan is the most used, probably because it is usually more precise than kidney ultrasound and more accessible than MRI. Performing chest X-ray at every check does not seem to alter the clinical outcome during AS. CONCLUSION: The minimal cancer-specific mortality does not seem to correlate with the follow-up scheme. Outside of growth rate and initial size, imaging features to predict outcome of RCC during AS are limited. Active surveillance of SRM is a well-established treatment option. However, standardized follow-up protocols are lacking. Prospective, randomized, trials to evaluate the best follow-up strategies are pending.