Conservative treatment of Peyronie's disease: a guide.

PURPOSE: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. METHODS: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. RESULTS: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. CONCLUSIONS: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.

Efficacy and safety of antegrade sclerotherapy for varicocele in pediatric patients: A systematic review.

OBJECTIVES: Antegrade sclerotherapy (Tauber's) procedure has been extensively used for the minimally-invasive treatment of varicocele; however, the results in the pediatric population are less defined. This systematic review evaluates the efficacy and safety of antegrade sclerotherapy for varicocele in the pediatric population. EVIDENCE ACQUISITION: The review was conducted following the PRISMA guidelines. Systematic research of available literature in English language from 1980 until May 2022 was conducted through EMBASE, MEDLINE, Cochrane Library, and NIH Registry of Clinical Trials. For each study, information was gathered regarding the study design, the inclusion/exclusion criteria, the indications for treatment, the success rate and the complications. When available, the details about sperm analysis were reported. EVIDENCE SYNTHESIS: The 10 studies were included in the final sample (564 patients). Median age of patients ranged 13.3-15.3 years. The indications for scleroembolization varied in the different studies, while most studies included patients with clinical G2-G3 varicocele and clinical symptoms or testicular asymmetry. The treatment was successful in 88%-98% of the patients, while the complication rate was <5%. CONCLUSION: Tauber's sclerotherapy is a safe and effective treatment for varicocele also in the pediatric population. Further studies with standardized inclusion criteria are needed to provide higher level of evidence and compare the outcomes of antegrade sclerotherapy with the other available techniques.

Sacrocolpopexy after sub-total hysterectomy vs. sacral hysteropexy for advanced urogenital prolapse: A propensity-matched study.

OBJECTIVE: To compare objective and subjective outcomes of laparoscopic sacral colpopexy with supracervical hysterectomy (L-SCP) and robotic sacral hysteropexy (R-SHP). METHODS: This is a multicenter retrospective propensity score matched study. In the period between January 2014 and December 2018, we enrolled 161 patients with apical prolapse stage 2 or above, alone or with multicompartment descensus. RESULTS: After propensity-match analysis, there were 44 women for each group. Patients of the two groups had similar preoperative characteristics. No difference was found in terms of estimated blood loss, hospital stay, operative time, and intraoperative or postoperative complications. Subjective success rate, 12 months after surgery, was statistically better in the L-SCP group (P = 0.034): 81.8% and 97.8% women had Patient Global Impression of Improvement scores less than 3, in R-SHP and L-SCP, respectively. The objective cure rate was high in both groups without any significant differences in recurrence rate (P = 0.266). CONCLUSION: Both procedures are safe and effective in pelvic organ prolapse treatment. Patients who no longer desire uterine preservation could be encouraged to consider L-SCP. R-SHP is an alternative in women who are strongly motivated to preserve their uterus in the absence of abnormal uterine findings.

Diagnosis of clinically significant prostate cancer after negative multiparametric magnetic resonance imaging.

Introduction: The diagnostic pathway after a negative magnetic resonance imaging (nMRI) exam is not clearly defined. The aim of the present study is to define the risk of prostate adenocarcinoma (PCa) at the prostate biopsy after a negative multiparametric magnetic resonance imaging (mpMRI) exam. Material and methods: Patients with nMRI Prostate Imaging Reporting & Data System (PI-RADS) ≤2 and without a previous diagnosis of PCa were identified among all patients undergoing mpMRI in a single referral center between 01/2016-12/2019. Detailed data about prostate biopsy after nMRI were collected, including any PCa diagnosis and clinically significant PCa diagnosis. [Gleason score (GS) ≥7]. In addition to descriptive statistics, uni and multivariable logistic regression assessed the potential predictors of any PCa and clinically significant prostate cancer (csPCa) at the biopsy after a negative mpMRI. Results: Of 410 patients with nMRI, 73 underwent saturation biopsy. Only prostate-specific antigen (PSA) levels were significantly higher in patients undergoing biopsy (5.2 ng/ml vs 6.4, p <0.001), while Prostate Cancer Research Foundation (SWOP - Stichting Wetenschappelijk Onderzoek Prostaatkanker) risk score and other variables did not differ. A total of 22 biopsies (30.1%) were positive for PCa, GS 6 was diagnosed in 14 patients, GS 7 in 3, GS 8 in 1 and GS 9-10 in 4. csPCa was found in 8 (11%) patients. No significant predictors of any PCa or csPCa were identified at multivariate regression analysis. Conclusions: Despite the good negative predictive value of mpMRI in the diagnosis of prostate cancer, 11% of the patients had csPCa. Specific predictive models addressing this setting would be useful.

Arterial Thrombotic Complications in COVID-19: A Case of Renal Infarction.

COVID-19 infection has been associated with thrombotic complications, especially venous thromboembolism. Although arterial thrombotic complications are rarely seen in these patients, we report the case of a 43-year-old patient who developed thrombosis of the main branch of the left renal artery, causing partial infarction of the left kidney associated with severe pain. He had no risk factors for thrombosis except for COVID-19 infection. We excluded any possible condition usually associated with renal artery thrombosis/embolism (i.e., cardiovascular, oncological, hematological, or rheumatic). The thrombosis resolved after a combination of anticoagulant and anti-platelet therapy. This case highlights the importance of the risk of recurrence of thrombosis in patients with a recent history of COVID-19, even after hospital discharge, improvement of the initial thrombotic event, and clearance of SARS-CoV-2 infection.

Metabolic syndrome and bladder cancer.

Metabolic syndrome (MetS) is a widely diffused dysmetabolism, well known to be associated with an increased cardiovascular risk. However, a growing burden of evidence links MetS with several malignancies, potentially influencing the onset, progression, and therapeutic response. In this work, we critically explored the relationship between MetS and bladder cancer through a narrative review, researching the most recent literature on the topic using PubMed, MEDLINE, and EMBASE. We found that the current evidence on the subject is heterogeneous and inconsistent, making it difficult to draw definitive conclusions. Furthermore, since MetS would be a modifiable oncological risk factor, more high-quality data is needed for tailored treatment of bladder cancer.

Clinical performance in ERN eUROGEN for penile, testicular, adrenal and soft tissue cancers.

BACKGROUND: European Reference Network (ERN) eUROGEN is a cross-border collaboration set up by the European Commission in 2017 aimed at tackling rare urogenital conditions, including cancers. OBJECTIVE: This report aims to assess ERN eUROGEN's operational activity with a focus on rare urogenital cancers. DESIGN, SETTING AND PARTICIPANTS: Data for descriptive analyses were collected retrospectively between 2013 and 2017, and prospectively between 2018 and 2020. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Operational indicators were set by the European Commission from 2018. Additionally, in 2019/20 centres self-assessed clinical service provision and provided clinical metrics for rare cancer specialist centres as established by experts. RESULTS AND LIMITATIONS: Results revealed that the cumulative rare urogenital cancer population increased 519.8% from 1,631 in 2013 to 10,109 in 2020. This may provide opportunities for research and creation of a large cancer registry. In total, ten centres met the clinical requirements for rare cancer specialist centres providing evidence of high-volume. Differences in data collection methods between centres limit further analyses. Other rare cancer data identified 39 panel discussions, three webinars, and eight publications. CONCLUSIONS: Whilst limitations to data analysis remain, ERN eUROGEN has demonstrated excellent operational performance with promising opportunities for rare cancer research.

Checkpoint Inhibition in Bladder Cancer: Clinical Expectations, Current Evidence, and Proposal of Future Strategies Based on a Tumor-Specific Immunobiological Approach.

In contrast with other strategies, immunotherapy is the only treatment aimed at empowering the immune system to increase the response against tumor growth. Immunotherapy has a role in the treatment of bladder cancer (BC) due to these tumors' high tumor mutational burden (TMB) and mostly prominent immune infiltrate. The therapy or combination has to be adjusted to the tumor's immunobiology. Recently, a new class of immunotherapeutic agents, immune checkpoint inhibitors (ICI), has shown potential in increasing treatment chances for patients with genitourinary cancers, improving their oncological outcomes. The clinical efficacy of ICI has been shown in both the first-line treatment of cisplatin-ineligible patients, with programmed death ligand 1 (PD-L1)-positive tumors (atezolizumab, pembrolizumab), and in second-line settings, for progression after platinum-based chemotherapy (atezolizumab, pembrolizumab, and nivolumab for FDA and EMA; durvalumab and avelumab for FDA alone). Predicting the response to ICI is important since only a subset of patients undergoing ICI therapy develop a concrete and lasting response. Most of the patients require a different therapy or therapy combination to achieve tumor control. The cancer immunity cycle provides a conceptual framework to assist therapy selection. Biomarkers to predict response to ICI must identify where the cancer immunity cycle is disrupted. We reviewed the current knowledge on ICI treatment in BC, going from basic science to current data and available clinical evidence. Secondly, a critical analysis of published data is provided, and an original panel of biomarkers able to predict response to ICI treatment, based on tumor-specific immune profiling, is proposed.

Patients with renal transplant and moderate-to-severe LUTS benefit from urodynamic evaluation and early transurethral resection of the prostate.

PURPOSE: To assess long-term renal function and micturition pattern of males submitted to transurethral resection of the prostate (TURP) for moderate-to-severe lower urinary tract symptoms (LUTS) after renal transplantation (RT). To investigate the role of clinical and urodynamic (UD) parameters for bladder outlet obstruction (BOO) diagnosis in these patients. METHODS: Retrospective data analysis of ≥ 50 years old patients who underwent RT between 01/2005 and 12/2016. Patients with moderate-to-severe LUTS after RT who underwent a urologic evaluation and a UD study were included. TURP was performed in case of BOO diagnosis. Kidney function and micturition patterns were evaluated before, 3, 12, 24, 36, and 48 months after TURP. Predictors of BOO were assessed at univariable and multivariable logistic regression models. Statistical analysis was performed with STATA16. RESULTS: 233 male patients ≥ 50 years underwent RT. 71/233 (30%) patients developed voiding LUTS. 52/71 (73%) patients with moderate-to-severe LUTS underwent UD. TURP was performed in 36/52 (69%) patients, with BOO diagnosis. Median (interquartile range) follow-up was 108 (75-136) months. Maximum flow at flowmetry (Qmax), International Prostate Symptom Score and post-voided residual volume improved significantly after surgery. Serum creatinine decreased and glomerular filtration rate improved significantly at follow-up, especially when TURP was performed ≤ 6 months from RT. At the multivariable model, bladder capacity ≥ 300 mL (OR = 1.74, CI 95% 1.03-3.15, p = 0.043) and detrusor pressure at Qmax (OR = 2.05, CI 95% 1.48-3.02, p = 0.035) were the independent predictors of BOO. CONCLUSION: RT patients with moderate-to-severe LUTS at risk for BOO and graft failure are better identified by UD than clinical parameters. Bladder capacity and voiding pressure are key for the early diagnosis of BOO.

Proof of Concept: Microinvasive AngioVac Approach in Renal Cell Carcinoma With Atrial Thrombosis.

The AngioVac system (AngioDynamics, Latham, NY) has already been described for treatment of thrombotic formations concerning the venous district and the tricuspid valve. We describe an innovative application of the AngioVac system to treat the inferior vena cava thrombosis associated with renal cell carcinoma. In a high surgical risk patient, we utilized a microinvasive and a modified venoarterial AngioVac circuit to remove the atrial thrombus, ensure temporary circulatory support during abdominal surgery, and prevent pulmonary embolism.

Management of penile cancer patients during the COVID-19 pandemic: An eUROGEN accelerated Delphi consensus study.

OBJECTIVES: To develop an international consensus on managing penile cancer patients during the COVID-19 acute waves. A major concern for patients with penile cancer during the coronavirus disease 2019 (COVID-19) pandemic is how the enforced safety measures will affect their disease management. Delays in diagnosis and treatment initiation may have an impact on the extent of the primary lesion as well as the cancer-specific survival because of the development and progression of inguinal lymph node metastases. MATERIALS AND METHODS: A review of the COVID-19 literature was conducted in conjunction with analysis of current international guidelines on the management of penile cancer. Results were presented to an international panel of experts on penile cancer and infection control by a virtual accelerated Delphi process using 4 survey rounds. Consensus opinion was defined as an agreement of ≥80%, which was used to reconfigure management pathways for penile cancer. RESULTS: Limited evidence is available for delaying penile cancer management. The consensus rate of agreement was 100% that penile cancer pathways should be reconfigured, and measures should be developed to prevent perioperative nosocomial transmission of COVID-19. The panel also reached a consensus on several statements aimed at reconfiguring the management of penile cancer patients during the COVID-19 pandemic. CONCLUSIONS: The international consensus panel proposed a framework for the diagnostic and invasive therapeutic procedures for penile cancer within a low-risk environment for COVID-19.

Successful Treatment of Vesicovaginal Fistulas via an Abdominal Transvesical Approach: A Single-center 50-yr Experience.

BACKGROUND: A vesicovaginal fistula (VVF) is an abnormal communication between bladder and vagina, as a result of traumatic events to the female pelvis. A VVF is a rare event and challenging to cure. Successful treatment can be achieved through an abdominal approach, especially in complex or recurrent cases. This approach has been used in our institution as the procedure of choice for the past 50yr. OBJECTIVE: To analyze the results of the management of VVFs in our institution and to highlight the key points for success. DESIGN, SETTING, AND PARTICIPANTS: A total of 138 patients with VVFs have been treated in our institution between 1969 and 2019. Up to now, this is the largest series reported so far on abdominal treatment of VVFs in the developed world. INTERVENTION: an abdominal transvesical approach has been performed as the procedure of choice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: to evaluate the factors influencing the success rate of the abdominal approach at the first closure attempt. Statistical analysis was performed using STATA software. RESULTS AND LIMITATIONS: In total, 124 (90%) patients were submitted to transabdominal repair (89 extraperitoneal; 71.8%), 113 (91.1%) presented with a VVF not associated with another fistula, and 36 (29.0%) had undergone previous unsuccessful treatments elsewhere. Successful closure was obtained in 111/118 (94.1%) patients at the first attempt, excluding external noncontinent urinary diversions. Follow-up was possible in 95 (76.6%) patients; 91 (95.8%) patients were dry. Statistical analysis showed a significant association between fistula size and length, and VVF site in the bladder and extraperitoneal approach. Success rate decreased with the number of previous attempts and did not vary with VVF etiology. CONCLUSIONS: The abdominal approach for the treatment of VVF has a high success rate. Standardization of the technique, identification of surgical key points, and centralization of care in centers with experience are critical. PATIENT SUMMARY: A vesicovaginal fistula (VVF) is a rare clinical condition, with a high impact on patients' quality of life. We report a large series of VVFs treated in our institution in the past 50yr. Key factors for success include proper surgical technique and centralization of care in centers with high experience.

Successful Multidisciplinary Repair of Severe Bilateral Uretero-Enteric Stricture with Inflammatory Reaction Extending to the Left Iliac Artery, after Robotic Radical Cystectomy and Intracorporeal Ileal Neobladder.

Uretero-enteric anastomotic strictures (UES) after robot-assisted radical cystectomy (RARC) represent the main cause of post-operative renal dysfunction. The gold standard for treatment of UES is open uretero-ileal reimplantation (UIR), which is often a challenging and complex procedure associated with significant morbidity. We report a challenging case of long severe bilateral UES (5 cm on the left side, 3 cm on the right side) after RARC in a 55 years old male patient who was previously treated in another institution and who came to our attention with kidney dysfunction and bilateral ureteral stents from the previous two years. Difficult multiple ureteral stent placement and substitutions had been previously performed in another hospital, with resulting urinary leakage. An open surgical procedure via an anterior transperitoneal approach was performed at our hospital, which took 10 h to complete, given the massive intestinal and periureteral adhesions, which required very meticulous dissection. A vascular surgeon was called to repair an accidental rupture that had occurred during the dissection of the external left iliac artery, involved in the extensive periureteral inflammatory process. Excision of a segment of the external iliac artery was accomplished, and an interposition graft using a reversed saphenous vein was performed. Bilateral ureteroneocystostomy followed, which required, on the left side, the interposition of a Casati-Boari flap harvested from the neobladder, and on the right side a neobladder-psoas-hitching procedure with intramucosal direct ureteral reimplantation. The patient recovered well and is currently in good health, as determined at his recent 24-month follow-up visit. No signs of relapse of the strictures or other complications were detected. Bilateral ureteral reimplantation after robotic radical cystectomy is a complex procedure that should be restricted to high-volume centers, where multidisciplinary teams are available, including urologists, endourologists, and general and vascular surgeons.

Outcome and quality of life of patients with augmented bladder or urinary diversion after kidney transplantation.

OBJECTIVE: The aim of the study was to assess results and quality of life after kidney transplant in adult patients with previously bladder augmentation or urinary diversion due to significant lower urinary tract dysfunction. MATERIALS AND METHODS: This cross-sectional study examines the outcome of 19 renal allografts transplanted in patients with augmented bladder or urinary diversion over a ten years period; moreover we submitted SF36 questionnaire to evaluate quality of life of these patients and compared the results with the general population. RESULT: Between January 1, 2005 and 31 December 2015 we performed 19/1093 renal transplantations in patients with abnormal lower urinary tract previously treated with bladder augmentation or bladder recycling. Current post-transplant follow-up was 47 months (range 18-188). No patient developed any episode of acute or chronic rejection. Mean serum creatinine after one year from transplant was 102 umol/L. Overall survival is 94.8% at the end of follow-up and graft survival is 89.6%. No significant differences emerged between patients undergoing transplant with lower urinary tract dysfunction and patients without, regarding to recurrent urinary tract infection. There was not statistically significant difference for vitality (p = 0.8088) and mental health (p = 0.8668). CONCLUSIONS: Presence of a previously augmented bladder or other lower urinary tract dysfunction treated in kidney transplant patients doesn't worsen the final outcome. Mental health and the vitality of these patients are similar to the general population.

Serenoa repens and Urtica dioica Fixed Combination: In-Vitro Validation of a Therapy for Benign Prostatic Hyperplasia (BPH).

Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention.

The Bladder EpiCheck Test as a Non-Invasive Tool Based on the Identification of DNA Methylation in Bladder Cancer Cells in the Urine: A Review of Published Evidence.

Recently, there has been a great effort to develop tests based on non-invasive urinary biomarkers (NMIBCs). These tests are based on the fact that NMIBCs are heterogeneous at the molecular level and can be divided into different molecular groups useful to predict prognosis and response to treatment. The assessment of epigenetic alterations, such as DNA methylation, represents a promising cancer biomarker. DNA methylation is an epigenetic modification that affects gene expression without modifying the DNA sequence. Several studies have highlighted the presence of methylated loci in the context of bladder cancer, indicating its potential application as a diagnostic and prognostic biomarker. One of the novel assays based on a DNA methylation profile, the Bladder EpiCheck, analyzes DNA from spontaneous urine, detecting disease-specific DNA methylation patterns in bladder cancer patients. This test, due to its non-invasive nature and highly promising performance could, in future, become an invaluable tool in the follow-up of bladder cancer patients. Potential new applications could include diagnosis and surveillance of upper-tract disease, for the replacement of invasive testing and ureteroscopy.

Efficacy of topical photodynamic therapy in the treatment of Erythroplasia of Queyrat.

Erythroplasia of Queyrat (EQ) is an intraepidermal carcinoma in situ presenting clinically as a sharply demarcated, slightly raised erythematosus plaque on the glans penis or the inner side of the foreskin. Various treatment modalities for EQ have been proposed, including electrocautery and curettage, topical 5-floururacil cream, imiquimod cream, isotretinoin, cryotherapy, laser therapy, radiotherapy, ingenol mebutate gel and Photodynamic Therapy (PDT). Most of these treatments are limited by low clearance rates and frequent relapses. Surgical treatment including local excision, Mohs micrographic surgery and partial or total penectomy, ensures adequate healing rates. However, discomfort consequent to surgical treatment might be unacceptable. Topical PDT using the methyl ester of 5- aminolaevulinic acid (MAL) is an established non-surgical treatment of cutaneous precancerous lesions and skin cancers. We present the case of a 60-year-old uncircumcised man affected by EQ of the penis successfully treated with MAL-PDT, performed five times, two weeks apart, with no recurrences after 6 years.

Relevance of the Endoscopic Evaluation in the Diagnosis of Bladder Pain Syndrome/Interstitial Cystitis.

OBJECTIVE: To assess the relevance of the endoscopic evaluation in clinically suspected cases of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC), using ESSIC criteria, established in 2008 by the European Society for the Study of Interstitial Cystitis (ESSIC). METHODS: We included all patients who underwent endoscopic evaluation between January 01, 2015 and October 31, 2019 for clinical suspicion of BPS/IC. Collected data included demographic and baseline clinical features, endoscopic appearance (prior and after hydrodistension), and bladder wall biopsy results, both defined according to ESSIC criteria. Data were cross tabulated to define ESSIC phenotypes, while subgroups and multivariate analyses were carried out to assess the influence of clinical variables on ESSIC phenotypes. RESULTS: Fifty-two subjects were included, mainly women (92%). Median age at evaluation was 45 (32.9-58.2) years. At hydrodistension, 21 patients (42%) had positive and 29 (58%) had negative findings. Grade 2-3 glomerulations were found in 18 patients, while Hunner lesions were reported only in 1 patient. Positive results at biopsy were found in 24 pts (51.1%), while negative in 23 (48.9%). Overall, the positive and negative concordance between hydrodistension and biopsy results was 78%. No significant differences in ESSIC subtypes were found after stratification based on clinical features and at multivariate analysis. Retrospective design is the main limitation. CONCLUSION: Cystoscopy with hydrodistension and biopsy do have a role in the diagnostic pathway of BPS/IC. However, results should be considered in the clinical context of the individual patient.

Spontaneous intra-adrenal massive hematoma: possible extreme evolution of a non-secreting untreated adrenal adenoma.

The spontaneous adrenal hematoma is a rare event. An 83-year-old male patient presented a 26-cm asymptomatic retroperitoneal mass of doubtful renal-adrenal origin. He had been evaluated 10 years before for an adrenal incidentaloma of 2.3 cm and had refused surgery when it had reached 7 cm. Later, the mass enlarged to 26 cm and was surgically removed through an open anterior approach. The histopathology showed a solid 4 kg mass of fibrinoid-hemorrhagic material, partially necrotic, mixed with adrenal tissue, with a well-vascularized capsule. No relapse is present at 6-month follow-up. This is the largest case described of spontaneous intra-adrenal hematoma in a case with previous non-secreting adrenal adenoma. The hematoma (a 4 kg mass) developed 10 years after the first diagnosis and exposed the patient to potential damage of the surrounding organs and to high-risk abdominal surgery. Long-term follow-up of non-secreting adrenal adenomas should be recommended.

Gender-Related Approach to Kidney Cancer Management: Moving Forward.

Men are more frequently diagnosed with kidney cancer than women, with a more aggressive histology, larger tumors, a higher grade and stage, and worse oncological outcomes. Smoking habits and sex steroid hormones seem to have a possible role in explaining these gender disparities. Moreover, the expression of genes involved in tumor growth and immune response in kidney cancer varies between men and women, having an impact on the gender-related response to oncological therapy, such as anti-angiogenic drugs and immunotherapy. Recent advances have been made in our understanding of the molecular and genetic mechanisms involved in kidney cancer, which could partially explain the gender differences, and they are summarized in this paper. However, other key mechanisms, which fully clarify the striking clinical gender-related differences observed in kidney cancer, are not completely understood at present. We reviewed and summarized the most relevant publications about the relationship between gender and kidney cancer. Efforts should be made to progress in bench and clinical research on gender-related signatures and disparities, and their impact on the clinical management of kidney cancer.