Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

Testicular Cancer Treatments and Sexuality: A Narrative Review.

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.

Age represents the main driver of surgical decision making in patients candidate to radical cystectomy.

BACKGROUND AND OBJECTIVES: Age might influence the choice of surgical approach, type of urinary diversion (UD) and lymph node dissection (LND) in patients candidate to radical cystectomy (RC) for urothelial bladder cancer (UBC). Similarly, age may enhance surgical morbidity and worsen perioperative outcomes. We tested the impact of age (octogenarian vs. younger patients) on surgical decision making and peri- and postoperative outcomes of RC. METHODS: Non-metastatic muscle-invasive UBC patients treated with RC at 18 high-volume European institutions between 2006 and 2021 were identified and stratified according to age (≥80 vs. <80 years). Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology guidelines recommendations were accomplished in collection and reporting of, respectively, intraoperative and postoperative complications. Multivariable logistic regression models (MVA) tested the impact of age on outcomes of interest. Sensitivity analyses after 1:3 propensity score matching were performed. RESULTS: Of 1955 overall patients, 251 (13%) were ≥80-year-old. Minimally invasive RC was performed in 18% and 40% of octogenarian and younger patients, respectively (p < 0.001). UD without bowel manipulation (ureterocutaneostomy, UCS) was performed in 31% and 7% of octogenarian and younger patients (p < 0.001). LND was delivered to 81% and 93% of octogenarian and younger patients (p < 0.001). At MVA, age ≥80 years independently predicted open approach (odds ratio [OR]: 1.55), UCS (OR: 3.70), and omission of LND (OR: 0.41; all p ≤ 0.02). Compared to their younger counterparts, octogenarian patients experienced higher rates of intraoperative (8% vs. 4%, p = 0.04) but not of postoperative complications (64% vs. 61%, p = 0.07). At MVA, age ≥80 years was not an independent predictor of length of stay, intraoperative or postoperative transfusions and complications, and readmissions (all p values >0.1). These results were replicated in sensitivity analyses. CONCLUSIONS: Age ≥80 years does not independently portend worse surgical outcomes for RC. However, octogenarians are unreasonably more likely to receive open approach and UCS diversion, and less likely to undergo LND.

Presumed Takotsubo syndrome is associated with high in-hospital mortality in very elderly frail females: a case series.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.

Ejection fraction at hospital admission stratifies mortality risk in HFmrEF patients aged ≥ 70 years: a retrospective analysis from a tertiary university institution.

BACKGROUND: During the last few years, increasing focus has been placed on heart failure with mildly reduced ejection fraction (HFmrEF), an intermediate phenotype from preserved to reduced ejection fraction (EF). However, clinical features and outcome of HFmrEF in elderly patients aged ≥ 70 yrs have been poorly investigated. METHODS: The present study retrospectively included all consecutive patients aged ≥ 70 yrs discharged from our Institution with a first diagnosis of HFmrEF, between January 2020 and November 2020. All patients underwent transthoracic echocardiography. The primary outcome was all-cause mortality, while the secondary one was the composite of all-cause mortality + rehospitalization for all causes over a mid-term follow-up. RESULTS: The study included 107 HFmrEF patients (84.3 ± 7.4 yrs, 61.7% females). Patients were classified as "old" (70-84 yrs, n = 55) and "oldest-old" (≥ 85 yrs, n = 52) and separately analyzed. As compared to the "oldest-old" patients, the "old" ones were more commonly males (58.2% vs 17.3%, p < 0.001), with history of coronary artery disease (CAD) (54.5% vs 15.4%, p < 0.001) and significantly lower EF (43.5 ± 2.7% vs 47.3 ± 3.6%, p < 0.001) at hospital admission. Mean follow-up was 1.8 ± 1.1 yrs. During follow-up, 29 patients died and 45 were re-hospitalized. Male sex (HR 6.71, 95% CI 1.59-28.4), history of CAD (HR 5.37, 95% CI 2.04-14.1) and EF (HR 0.48, 95% CI 0.34-0.68) were independently associated with all-cause mortality in the whole study population. EF also predicted the composite of all-cause mortality + rehospitalization for all causes. EF < 45% was the best cut-off value to predict both outcomes. CONCLUSIONS: EF at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFmrEF patients over a mid-term follow-up.

Carboplatin-based adjuvant chemotherapy versus observation after radical cystectomy in patients with pN1-3 urothelial bladder cancer.

PURPOSE: To test the impact of carboplatin-based ACT on overall survival (OS) in patients with pN1-3 cM0 BCa. METHODS: A retrospective analysis was conducted on 1057 patients with pTany pN1-3 cM0 urothelial BCa treated with or without carboplatin-based ACT after radical cystectomy and bilateral lymph-node dissection between 2002 and 2018 at 12 European and North-American hospitals. No patient received neoadjuvant chemotherapy or radiation therapy. Only patients with negative surgical margins at surgery were included. A 3:1 propensity score matching (PSM) was performed using logistic regression to adjust for baseline characteristics. Univariable and multivariable Cox regression analyses were used to predict the effect of carboplatin-based ACT on OS. The Kaplan-Meier method was used to display OS in the matched cohort. RESULTS: Of the 1057 patients included in the study, 69 (6.5%) received carboplatin-based ACT. After PSM, 244 total patients were identified in two cohorts that did not differ for baseline characteristics. Death was recorded in 114 (46.7%) patients over a median follow-up of 19 months. In the multivariable Cox regression analyses, increasing age at surgery (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.06, p < 0.001) and increasing number of positive lymph nodes (HR 1.06, 95% CI 1.01-1.07, p = 0.02) were independent predictors of worse OS. The delivery of carboplatin-based ACT was not predictive of improved OS (HR 0.67, 95% CI 0.43-1.04, p = 0.08). The main limitations of this study are its retrospective design and the relatively low number of patients involved. CONCLUSIONS: Carboplatin-based might not improve OS in patients with pN1-3 cM0 BCa. Our results underline the need for alternative therapies for cisplatin-ineligible patients.

Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.

PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.

Micropapillary bladder cancer: an evolving biology.

PURPOSE OF REVIEW: To summarize a comprehensive overview of more recent evidence on micropapillary bladder cancer (MPBC), focusing on actual incidence, clinical features, therapeutic strategies, and prognosis. RECENT FINDINGS: MPBC generally exhibits an aggressive behaviour compared with pure urothelial carcinoma (pUC) with advances in tumour stage and nodal and distant spread at diagnosis. Due to its rarity and presence of only small sample size and retrospective studies, no consensus currently exists regarding the most effective therapeutic strategy to be performed among nonmuscle-invasive (conservative treatment versus immediate radical cystectomy) and muscle-invasive MPBC (neoadjuvant therapy versus upfront radical cystectomy versus adjuvant chemotherapy). SUMMARY: The incidence of MPBC is recently increased according to latter literature, ranging from 2.9 to 7.6% of all bladder cancer. Despite its aggressive behaviour at time of presentation, more recent evidence fails to demonstrate a significant association between MPBC and worse outcomes compared with pUC when adjusted for clinical and pathological features. According to latter evidence, MPBC pathological response to NAC appears to be unsatisfactory compared with pUC patients while neoadjuvant immunotherapy with Pembrolizumab may represent an effective treatment among MPBC patients, based on PD-L1 and TMB expression.

Lynch syndrome in urological practice: diagnosis, therapeutic strategies, and screening for upper tract urothelial carcinoma.

PURPOSE OF REVIEW: To provide a comprehensive overview of diagnosis, treatment, and screening for upper tract urothelial carcinoma (UTUC) among Lynch syndrome patients. RECENT FINDINGS: Lynch syndrome is an autosomal dominant disorder resulting from the germline mutation in the mismatch repair (MMR) system. The Lynch syndrome predisposes to early onset of a broad spectrum of tumours, among which UTUC represents the third most frequent malignancy. Since up to 10% of UTUC can be attributed to Lynch syndrome, a correct recognition of this disease provides the opportunity for patients and their relatives to be properly treated for UTUC and to be followed up for other Lynch syndrome-related malignancies. SUMMARY: UTUC patients less than 65 years, or UTUC patients with personal history of Lynch syndrome-related cancer, or with one first-degree relative (FDR) less than 50 years with Lynch syndrome-related cancer, or two FDRs with Lynch syndrome-related cancer regardless of age should be referred to molecular testing and subsequent DNA sequencing to confirm Lynch syndrome diagnosis. Considering the increased risk of metachronous recurrence, treatments other than radical nephroureterectomy, such as ureteroscopic laser ablation may represent valuable therapeutic strategies. As Lynch syndrome patients exhibit an approximate 14-fold increased risk of developing UTUC compared with general population, expert recommendations are urgently required in order to point out appropriate screening protocols.

Prevalence and clinical outcome of main echocardiographic and hemodynamic heart failure phenotypes in a population of hospitalized patients 70 years old and older.

BACKGROUND: Heart failure (HF) echocardiographic and hemodynamic categories are poorly characterized in the elderly. We aimed to evaluate the prevalence and clinical outcomes of echocardiographic and hemodynamic HF phenotypes in a consecutive series of hospitalized patients aged ≥ 70 years. METHODS: All consecutive patients ≥ 70 years old discharged from the Internal Medicine Unit of our Hospital with a diagnosis of HF, between January and November 2020, entered this retrospective study. All patients underwent physical examination, complete blood tests, chest X-ray and transthoracic echocardiography. At 1-year follow-up, we evaluated the occurrence of the composite outcome of all-cause mortality and re-hospitalization. RESULTS: Two hundred and sixty-one patients (86.3 ± 6.4 years, 60.9% women) were retrospectively analyzed. From the study group, 106 "old" (70-84 years) and 155 "oldest-old" (≥ 85 years) patients were separately analyzed. A total of 169 (64.7%) patients reported the composite outcome during follow-up: 41 (15.7%) died and 128 (49.0%) were re-hospitalized. At 1-year follow-up, survival analysis did not show any statistically significant difference between age groups (p = 0.31) and between HF echocardiographic categories (p = 0.34), whereas HF patients with "cold-dry" phenotype had significantly poorer survival compared to the other hemodynamic subtypes (p < 0.001). Male sex (HR 1.44, 95% CI 1.04-1.98), "cold-dry" phenotype (HR 3.90, 95% CI 1.73-8.77), high sodium level (HR 1.03, 95% CI 1.01-1.04) and low estimated glomerular filtration rate (eGFR) (HR 0.98, 95% CI 0.97-0.99) were independently associated with the outcome occurrence. CONCLUSIONS: Male sex, "cold-dry" phenotype, high sodium level and low eGFR are the main adverse prognostic indicators over a mid-term follow-up in hospitalized patients aged ≥ 70 years.

CHA2DS2-VASc score stratifies mortality risk in heart failure patients aged 75 years and older with and without atrial fibrillation.

BACKGROUND: During the last decade, the CHA2DS2-VASc score has been associated with adverse clinical outcomes in several cardiovascular (CV) and non-cardiovascular diseases beyond atrial fibrillation (AF). Whether the CHA2DS2-VASc score stratifies mortality risk in elderly patients with AF and without AF is not well established. METHODS: All consecutive patients aged ≥ 75 yrs hospitalized due to heart failure (HF), between January 2020 and November 2020, were retrospectively enrolled. All patients underwent physical examination, blood tests, electrocardiography and conventional transthoracic echocardiography. Primary endpoint was all-cause mortality, while secondary endpoint was the composite of all-cause mortality + rehospitalizations for all causes over mid-term follow-up. RESULTS: The study included 261 HF patients (86.3 ± 6.4 years, 60.5% females). 85 AF and 176 non-AF patients were separately analyzed. Compared to non-AF patients, those with AF had significantly higher CHA2DS2-VASc score (5.6 ± 1.4 vs 5.1 ± 1.4, p = 0.007) and lower ejection fraction (47.4 ± 16.5 vs 56.7 ± 15.1%, p < 0.001). Mean follow-up was 1.7 ± 0.5 yrs. During follow-up, 96 patients died (58.3% due to CV causes) and 79 were rehospitalized (58.2% due to CV causes). CHA2DS2-VASc score was independently associated with all-cause mortality in whole study population (HR 1.61, 95% CI 1.36-1.92) and in both AF (HR 1.41, 95% CI 1.09-1.82) and non-AF patients (HR 1.84, 95% CI 1.40-2.40). CHA2DS2-VASc score also predicted the secondary endpoint in the same study groups. CHA2DS2-VASc score ≥ 5 was the best cut-off value for predicting both outcomes. CONCLUSION: At mid-term follow-up, a CHA2DS2-VASc score ≥ 5 predicts increased risk of all-cause mortality and re-hospitalizations for all causes in elderly HF patients, regardless of AF.

Oncologic Surveillance for Variant Histology Bladder Cancer after Radical Cystectomy.

PURPOSE: Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC). MATERIALS AND METHODS: Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site. RESULTS: Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p <0.001) and shorter median time to recurrence (88 vs 123 months, p <0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals. CONCLUSIONS: VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

Treatment Outcomes for Men with Clinical Stage II Nonseminomatous Germ Cell Tumours Treated with Primary Retroperitoneal Lymph Node Dissection: A Systematic Review.

CONTEXT: Guidelines recommend primary retroperitoneal lymph node dissection (RPLND) as a treatment option for tumour marker-negative stage II nonseminomatous germ cell tumour (NSGCT). OBJECTIVE: To review the literature on oncological outcomes for men with stage II NSGCT treated with RPLND. EVIDENCE ACQUISITION: A systematic review of studies describing clinicopathological outcomes following primary RPLND in stage II NSGCT was conducted in the MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. Baseline data, perioperative and postoperative parameters, and oncological outcomes were collected. EVIDENCE SYNTHESIS: In total, 12 of 4387 studies were included, from which we collected data for 835 men. Among men with clinical stage II NSGCT, pathological stage II was confirmed in 615 of 790 patients (78%). Most studies administered adjuvant chemotherapy in cases with large lymph nodes, multiple affected lymph nodes, or persistently elevated tumour markers. Recurrence was observed in 12-40% of patients without adjuvant chemotherapy and 0-4% of patients who received adjuvant chemotherapy. CONCLUSIONS: The literature describing RPLND in clinical stage II NSGCT is heterogeneous and no meta-analysis was possible, but RPLND can provide accurate staging and may be curative in selected patients. PATIENT SUMMARY: We reviewed the literature to summarise results after surgical removal of enlarged lymph nodes in the back of the abdomen in men with testis cancer. This procedure provides accurate information on how far the cancer has spread and may provide a cure in selected patients.

Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis.

BACKGROUND: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. METHODS: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. RESULTS: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. CONCLUSION: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

Genitourinary manifestations of Lynch syndrome in the urological practice.

Objective: Lynch syndrome (LS) is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM gene. From a clinical perspective, LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general population. We aimed to provide a comprehensive overview of all the genitourinary manifestations of LS, focusing on incidence, diagnosis, clinical features, therapeutic strategies, and screening protocols. Methods: Previous literature was assessed through Medline, Scopus, and Google Scholar databases. A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was provided. Results: In the LS tumor spectrum, upper tract urothelial carcinoma (UTUC) represents the third most frequent malignancy, and the first most common cancer in the urological field, with an approximately 14-fold increased risk of developing UTUC compared to general population. LS diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process, including (i) clinical criteria, (ii) molecular testing, and (iii) genetic testing to confirm the hereditary disorder. The current European Association of Urology (EAU) guidelines recommend to perform molecular testing among UTUC patients under 65 years old, or UTUC patients with personal history of LS-related tumor, or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor, or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of onset. Newly diagnosed LS patients should be referred to a multidisciplinary management, including gastroenterologists and gynecologists. Finally, considering the increased risk of metachronous recurrence, treatments other than radical nephroureterectomy may be a valuable therapeutic alternative. Whether urological malignancies other than UTUC should be included in the LS tumor spectrum is still controversial. Conclusion: Considering the strict association between UTUC and LS, we believe that the urologist should recognize patients at increased risk for hereditary disease according to current EAU clinical criteria and address them to a comprehensive diagnostic algorithm, including molecular evaluation and genetic testing. To date, literature lacks clear evidence regarding the role of LS in developing bladder cancer, prostate cancer, or renal cell carcinoma, and current data are still inconclusive, highlighting the urgent need for further studies.