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Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects., Competing Interests: Disclosure None of the authors has conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to compare the clinical outcomes of robot-assisted partial nephrectomy (RAPN) and image-guided percutaneous cryoablation (IG-PCA) for clinical T1 renal cell carcinoma., Materials and Methods: We conducted a retrospective analysis of 679 patients with clinical T1 renal cell carcinoma treated with RAPN or IG-PCA between 2012 and 2021. Propensity scores were calculated via logistic analysis to adjust for imbalances in baseline characteristics. We compared oncological and functional outcomes between the 2 treatment groups., Results: Following the matching process, 108 patients were included in each group. No patient in the RAPN group developed local recurrence. In the IG-PCA group, three patients experienced local tumor progression. The patients underwent salvage thermal ablations by the secondary technique; 2 underwent IG-PCA and 1 underwent microwave ablation, resulting in a local control rate of 100%. The Kaplan-Meier analysis showed no statistically significant differences between the groups in terms of 5-year recurrence-free survival, metastasis-free survival, and overall survival (log-rank test; P = 0.11, P = 0.64, and P = 0.17, respectively). No significant differences were observed in the 2 treatments in major and overall complication rates (P = 0.75 and P = 0.82, respectively). Both groups showed similar rates of less than 10% estimated glomerular filtration rate decline at 12 months post-treatment and 5-year renal function preservation rates (P = 0.88 and P = 0.38, respectively)., Conclusions: IG-PCA demonstrated oncological outcomes comparable to those of RAPN. RAPN addressed the disadvantages of conventional procedures and allowed for safety outcomes comparable to IG-PCA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In thermogenic brown and beige adipocytes, the proton gradient formed by energy derived from nutrients such as lipids and carbohydrates is consumed by uncoupling protein-1 (UCP-1), resulting in thermogenesis without ATP production in the mitochondria. Accordingly, increased UCP-1 expression represents a crucial aspect of dietary management for individuals with overweight and obesity. Myricetin and its glycoside, myricitrin, are food-derived flavonoids that possess various beneficial effects. This is the first study to examine the effects of myricetin and myricitrin on the inflammation-inhibited expression of Ucp-1 using a modified cell-based assay with conditioned medium (CM). The CM derived from lipopolysaccharide (LPS)-activated RAW264.7 macrophages was observed to inhibit the Ucp-1 expression induced by adrenergic stimulation in 10T1/2 adipocytes. Conversely, the CM derived from activated macrophages treated with myricetin or myricitrin reversed this inhibition of Ucp-1 expression. Subsequently, the direct effects of both the compounds on basal and adrenaline-induced expression of Ucp-1 were investigated. In contrast to a previous report, myricetin and myricitrin did not increase the basal Ucp-1 mRNA expression in 10T1/2 adipocytes when treated during the differentiation-promoting period. However, we have found for the first time that both compounds enhanced the adrenergic sensitivity of 10T1/2 adipocytes when treated during the differentiation-inducing period. These results indicate that myricetin and myricitrin have indirect effects on inflammation-induced suppression and direct effects on adrenergic sensitivity, suggesting a novel mechanism that both compounds increase Ucp-1 expression in vivo by both indirect and direct effects, rather than by affecting basal expression., Competing Interests: Declaration of competing interest The authors declare no financial or personal relationships that may be considered potential competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few., Methods: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared., Results: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8)., Conclusions: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making., Competing Interests: Declaration of competing interest Takahiro Kimura is a paid consultant/advisor of Astellas, Bayer, Janssen, Sanofi and Takeda. The other authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Impella (Abiomed, Danvers, MA, USA) is a percutaneous ventricular assist device commonly used in cardiogenic shock, providing robust hemodynamic support, improving the systemic circulation, and relieving pulmonary congestion. Maintaining adequate left ventricular (LV) filling is essential for optimal hemodynamic support by Impella. This study aimed to investigate the impact of pulmonary vascular resistance (PVR) and right ventricular (RV) function on Impella-supported hemodynamics in severe biventricular failure using cardiovascular simulation., Methods: We used Simulink® (Mathworks, Inc., Natick, MA, USA) for the simulation, incorporating pump performance of Impella CP determined using a mock circulatory loop. Both systemic and pulmonary circulation were modeled using a 5-element resistance-capacitance network. The four cardiac chambers were represented by time-varying elastance with unidirectional valves. In the scenario of severe LV dysfunction (LV end-systolic elastance set at a low level of 0.4 mmHg/mL), we compared the changes in right (RAP) and left atrial pressures (LAP), total systemic flow, and pressure-volume loop relationship at varying degrees of RV function, PVR, and Impella flow rate., Results: The simulation results showed that under low PVR conditions, an increase in Impella flow rate slightly reduced RAP and LAP and increased total systemic flow, regardless of RV function. Under moderate RV dysfunction and high PVR conditions, an increase in Impella flow rate elevated RAP and excessively reduced LAP to induce LV suction, which limited the increase in total systemic flow., Conclusions: PVR is the primary determinant of stable and effective Impella hemodynamic support in patients with severe biventricular failure., Competing Interests: Declaration of competing interest Matsushita H, Nishikawa T, Unoki T, Yokota S, Sato K, Morita H, Yoshida Y, Fukumitsu M, Nishiura A, Uemura K, Kawada T, Kikuchi A, and Yamaura K, declare no conflicts of interest. Saku K received research funding from Abiomed Japan K.K., NTT Research, Inc., Asahi Kasei ZOLL Medical Corporation, Neuroceuticals Inc., and Zeon Medical Inc. and honoraria from Abiomed Japan K.K., Mallinckrodt Pharma K.K., and Ono Pharmaceutical Co., Ltd., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Concomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab., Patients and Methods: This retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan-Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes., Results: Overall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan-Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs., Conclusion: PPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids., Competing Interests: Disclosure The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: We aimed to assess the prognostic value of tumor infiltrating lymphocytes (TILs) in patients with bladder cancer (BC) after radical cystectomy (RC)., Materials and Methods: We searched Pubmed, Web of Science and Scopus in April 2022 to identify studies assessing the prognostic value of TILs, including a subset of lymphocytes (eg, CD3, CD8, FOXP3), after RC. The endpoints were overall survival and recurrent free survival. Subgroup analyses were performed based on the evaluation method for TILs (ie, CD3, CD8, FOXP3, HE staining)., Results: Overall, 9 studies comprising 1413 patients were included in this meta-analysis. The meta-analysis revealed that elevated expressions of TILs were significantly associated with favorable OS (pooled hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.51-0.83) and RFS (pooled HR: 0.48, 95% CI: 0.35-0.64). In subgroup analyses, high CD8+ TILs were also associated with favorable OS (HR: 0.51, 95% CI: 0.33-0.80) and RFS (pooled HR: 0.53, 95% CI: 0.36-0.76). Among 3 studies comprising 146 patients, high intratumoral TILs were significantly associated with favorable OS (pooled HR: 0.34, 95% CI: 0.19-0.60)., Conclusion: TILs are useful prognostic markers in patients treated with RC for BC. Although the prognostic value of TILs is varied, depending on the subset and infiltration site, CD8+ TILs and intratumoral TILs are associated with oncologic outcomes. Further studies are warranted to explicate the predictive value of TILs on the response to perioperative systemic therapy to help clinical decision-making in patients with BC., Competing Interests: Disclosure All authors state that they have no conflict of interest that might bias this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC., Methods: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines., Results: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses., Conclusion: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The activation of peroxisome proliferator-activated receptor alpha (PPARα), a ligand-dependent transcription factor that regulates lipid oxidation-related genes, has been employed to treat hyperlipidemia. Emerging evidence indicates that Ppara gene expression decreases in adipose tissue under obese conditions; however, the underlying molecular mechanisms remain elusive. Here, we demonstrate that nitric oxide (NO) suppresses Ppara expression by regulating its promoter activity via suppression of specificity protein 1 (Sp1) transcriptional activity in adipocytes. NO derived from lipopolysaccharide (LPS) -activated macrophages or a NO donor (NOR5) treatment, suppressed Ppara mRNA expression in 10T1/2 adipocytes. In addition, Ppara transcript levels were reduced in the white adipose tissue (WAT) in both acute and chronic inflammation mouse models; however, such suppressive effects were attenuated via a nitric oxide synthase 2 (NOS2) inhibitor. Endoplasmic reticulum (ER) stress inhibitors attenuated the NO-induced repressive effects on Ppara gene expression in 10T1/2 adipocytes. Promoter mutagenesis and chromatin immunoprecipitation assays revealed that NO decreased the Sp1 occupancy in the proximal promoter regions of the Ppara gene, which might partially result from the reduced Sp1 expression levels by NO. This study delineated the molecular mechanism that modulates Ppara gene transcription upon NO stimulation in white adipocytes, suggesting a possible mechanism for the transcriptional downregulation of Ppara in WAT under obese conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: There is a persistent lack of validated biomarkers that identify patients most likely to benefit from neoadjuvant chemotherapy (NAC) in urothelial carcinoma of the bladder (UCB). Therefore, the purpose of this study was to investigate the predictive and prognostic impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) in UCB patients treated with NAC and radical cystectomy (RC)., Patients and Methods: We conducted a retrospective analysis of an international-multicenter database comprising 404 UCB patients staged cT2-4N0-3M0. The cohort was split into low and high NLR using an optimal cutoff value determined by maximizing Youden's index. Logistic and Cox regression analyses were performed with respect to several clinical endpoints. The discriminative ability of the models and the additive discriminative value of NLR was assessed by calculating the area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA)., Results: A total of 169 patients (41.8%) had a high NLR, which was associated with a decreased probability of complete response (CR, OR: 0.24 [95% CI, 0.13-0.42], P < .001) and/or partial response (PR, OR: 0.33 [95% CI, 0.21-0.49], P < .001). Adding the NLR to predictive reference models significantly improved their accuracy for the prediction of both CR and PR. A high NLR was associated with poor survival outcomes in the pretreatment setting, however, it didn't meaningfully change the C-index based on the model., Conclusion: We confirmed that an elevated NLR is an independent and clinically significant predictor of response to NAC and adverse pathological features in UCB treated with NAC plus RC. The accuracy of this biomarker in the age of immunotherapy warrants further evaluation., Competing Interests: Disclosure Shahrokh F. Shariat received follows: Honoraria: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, Takeda; Consulting or Advisory Role: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Takeda; Speakers Bureau: Astellas, Astra Zeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, Takeda. The other authors declare no conflicts of interest associated with this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study aimed to assess both efficacy and safety outcomes of lowering the dose of BCG compared to intravesical chemotherapies in non-muscle-invasive bladder cancer (NMIBC) patients using a systematic review, meta-analysis, and network meta-analysis approach. A comprehensive literature search was performed through Pubmed®, Web of Science™, and Scopus® in December 2022 to identify randomized controlled trials comparing the oncologic and/or safety outcomes of reduced dose intravesical BCG and/or intravesical chemotherapies according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. The outcomes of interest were risk of recurrence, progression, treatment-related adverse events, and discontinuation. Overall, 24 studies were eligible for quantitative synthesis. Among 22 studies that adopted induction followed by maintenance intravesical therapy, with reference to the lower-dose BCG, epirubicin was associated with a significantly higher risk of recurrence (Odds ratio [OR]: 2.82, 95% CI: 1.54-5.15), but not other intravesical chemotherapies. There were no significant differences in risk of progression among the intravesical therapies. On the other hand, standard-dose BCG was associated with a higher risk of any AEs (OR: 1.91, 95% CI: 1.07-3.41) but other intravesical chemotherapies had a comparable risk of AEs compared to lower-dose BCG. The discontinuation rate did not significantly differ between lower-dose and standard-dose BCG (OR: 1.40, 95% CI: 0.81-2.43) as well as other intravesical. According to the surface under the cumulative ranking curve, gemcitabine, and standard-dose BCG were preferable to lower-dose BCG in terms of recurrence risk; gemcitabine was also preferable to lower-dose BCG in terms of risk of AEs. In patients with NMIBC, lowering the dose of BCG decreases the risks of AEs and discontinuation rate compared to standard-dose BCG, but there is no difference in these endpoints compared to other intravesical chemotherapies. Standard-dose of BCG is preferred for all intermediate and high-risk NMIBC patients based on oncologic efficacy; however, lower-dose BCG and intravesical chemotherapies, especially gemcitabine, could be considered a reasonable alternative to BCG in selected patients who suffer from significant AEs or in case standard-dose BCG is not available., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel., Methods: PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel., Results: Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56-0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33-2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62-2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25-1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27-2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28-1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00-2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52-12.72), low albumin (pooled HR:1.09, 95% CI: 1.05-1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20-1.99)., Conclusions: Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit., Competing Interests: Conflicts of interest Shin Egawa is a paid consultant/advisor of Takeda, Astellas, AstraZeneca, Sanofi, Janssen, and Pfizer. Takahiro Kimura is a paid consultant/advisor of Astellas, Bayer, Janssen and Sanofi. Shahrokh F. Shariat received follows: Honoraria: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, Takeda Consulting or Advisory Role: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Takeda Speakers Bureau: Astellas, Astra Zeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, Takeda The other authors declare no conflicts of interest associated with this manuscript., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Oligometastatic prostate cancer (omPCa) is a novel intermediate disease state characterized by a limited volume of metastatic cells and specific locations. Accurate staging is paramount to unmask oligometastatic disease, as provided by prostate-specific membrane antigen-positron emission tomography. Driven by the results of prospective trials employing conventional and/or modern staging modalities, the treatment landscape of omPCa has rapidly evolved over the last years. Several treatment-related questions comprising the concept of precision strikes are under development. For example, beyond systemic therapy, cohort studies have found that cytoreductive radical prostatectomy (CRP) can confer a survival benefit in select patients with omPCa. More importantly, CRP has been consistently shown to improve long-term local symptoms when the tumor progresses across disease states due to resistance to systemic therapies. Metastasis-directed treatments have also emerged as a promising treatment option due to the visibility of oligometastatic disease and new technologies as well as treatment strategies to target the novel PCa colonies. Whether metastases are present at primary cancer diagnosis or detected upon biochemical recurrence after treatment with curative intent, targeted yet decisive elimination of disseminated tumor cell hotspots is thought to improve survival outcomes. One such strategy is salvage lymph node dissection in oligorecurrent PCa which can alter the natural history of progressive PCa. In this review, we will highlight how refinements in modern staging modalities change the classification and treatment of (oligo-)metastatic PCa. Further, we will also discuss the current role and future directions of precision surgery in omPCa., Competing Interests: Disclosure MP reports that he has received a research grant from the Austrian Urological Association; support for attending the Austrian Urological Association’s yearly meeting; speaker honoraria from Astellas, Janssen, and MedMedia; and an honorarium from Spectra for attending an Advisory Board. MP was a board member of the Austrian Urological Association from 2018 to 2021. SFS received the following: honoraria: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Roche, Takeda; consulting or advisory role: Astellas, AstraZeneca, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Takeda; speaker’s bureau: Astellas, Astra Zeneca, Bayer, BMS, Ferring, Ipsen, Janssen, MSD, Olympus, Pfizer, Richard Wolf, Roche, Takeda. All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess the differential clinical outcomes of patients treated with partial nephrectomy (PN) vs. those treated with ablation therapy (AT) such as radiofrequency ablation, cryoablation and microwave ablation for cT1b compared to cT1a renal tumors., Materials and Methods: Multiple databases were searched for articles published before August 2021. Studies were deemed eligible if they compared clinical outcomes in patients who underwent PN with those who underwent AT for cT1a and/or cT1b renal tumors., Results: Overall, 27 studies comprising 13,996 patients were eligible for this meta-analysis. In both cT1a and cT1b renal tumors, there was no significant difference in the percent decline of estimated glomerular filtration rates or in the overall/severe complication rates between PN and AT. Compared to AT, PN was associated with a lower risk of local recurrence in both patients with cT1a and cT1b tumors (cT1a: pooled risk ratio [RR]; 0.43, 95% confidence intervals [CI]; 0.28-0.66, cT1b: pooled RR; 0.41, 95%CI; 0.23-0.75). Subgroup analyses regarding the technical approach revealed no statistical difference in local recurrence rates between percutaneous AT and PN in patients with cT1a tumors (pooled RR; 0.61, 95%CI; 0.32-1.15). In cT1b, however, PN was associated with a lower risk of local recurrence (pooled RR; 0.45, 95%CI; 0.23-0.88). There was no difference in distant metastasis or cancer mortality rates between PN and AT in patients with cT1a, or cT1b tumors., Conclusions: AT has a substantially relevant disadvantage with regards to local recurrence compared to PN, particularly in cT1b renal tumors. Despite the limitations inherent to the nature of retrospective and unmatched primary cohorts, percutaneous AT could be used as a reasonable alternative treatment for well-selected patients with cT1a renal tumors., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)