BACKGROUND: The role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease. OBJECTIVE: We aimed to assess the predictors of prostate-specific antigen (PSA) persistence in surgically managed PCa patients with lymphadenopathies on a PSMA PET/CT scan by integrating clinical, magnetic resonance imaging (MRI), and PSMA PET/CT parameters. DESIGN, SETTING, AND PARTICIPANTS: We identified 519 patients treated with RP and extended lymph node dissection, and who received preoperative PSMA PET between 2017 and 2022 in nine referral centers. Among them, we selected 88 patients with nodal uptake at preoperative PSMA PET (miTxN1M0). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome was PSA persistence, defined as a PSA value of ≥0.1 ng/ml at the first measurement after surgery. Multivariable logistic regression models tested the predictors of PSA persistence. Covariates consisted of biopsy International Society of Urological Pathology (ISUP) grade group, clinical stage at MRI, and number of positive spots at a PET/CT scan. A regression tree analysis stratified patients into risk groups based on preoperative characteristics. RESULTS AND LIMITATIONS: Overall, lymph node invasion (LNI) was detected in 63 patients (72%) and 32 (36%) experienced PSA persistence after RP. At multivariable analyses, having more than two lymph nodal positive findings at PSMA PET, seminal vesicle invasion (SVI) at MRI, and ISUP grade group >3 at biopsy were independent predictors of PSA persistence (all p < 0.05). At the regression tree analysis, patients were stratified in four risk groups according to biopsy ISUP grade, number of positive findings at PET/CT, and clinical stage at MRI. The model depicted good discrimination at internal validation (area under the curve 78%). CONCLUSIONS: One out of three miN1M0 patients showed PSA persistence after surgery. Patients with ISUP grade 2-3, as well as patients with organ-confined disease at MRI and a single or two positive nodal findings at PET are those in whom RP may achieve the best oncological outcomes in the context of a multimodal approach. Conversely, patients with a high ISUP grade and extracapsular extension or SVI or more than two spots at PSMA PET should be considered as potentially affected by systemic disease upfront. PATIENT SUMMARY: Our novel and straightforward risk classification integrates currently available preoperative risk tools and should, therefore, assist physician in preoperative counseling of men candidates for radical treatment for prostate cancer with positive lymph node uptake at prostate-specific membrane antigen positron emission tomography.

• Klíčová slova
• Multiparametric magnetic resonance imaging, Nomogram, Prostate cancer, Prostate-specific antigen persistence, Prostate-specific membrane antigen positron emission tomography, Risk category,
• MeSH
• lidé MeSH
• lymfadenopatie * patologie   chirurgie   MeSH
• lymfatické metastázy patologie   MeSH
• lymfatické uzliny diagnostické zobrazování   chirurgie   patologie   MeSH
• magnetická rezonanční tomografie MeSH
• nádory prostaty * diagnostické zobrazování   chirurgie   patologie   MeSH
• PET/CT metody   MeSH
• pozitronová emisní tomografie MeSH
• prostata diagnostické zobrazování   chirurgie   patologie   MeSH
• prostatektomie MeSH
• prostatický specifický antigen MeSH
• semenné váčky patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• prostatický specifický antigen MeSH

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.

• Klíčová slova
• cN+, induction chemotherapy, lymph node-positive, radical cystectomy, template, urinary bladder neoplasms, urothelial cancer,
• MeSH
• cystektomie MeSH
• lidé MeSH
• lokální recidiva nádoru * patologie   MeSH
• lymfadenektomie MeSH
• lymfatické uzliny chirurgie   patologie   MeSH
• nádory močového měchýře * farmakoterapie   chirurgie   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

OBJECTIVES: To address the association of perioperative surgical checklist across variable surgical expertise with transurethral resection of bladder tumour (TURBT) accuracy and oncological outcomes in non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We relied on our prospective collaborative database of patients treated with TURBT between 2012 and 2017. Surgical experience was stratified into three groups: resident vs young vs expert consultants. The association of surgical experience with detrusor muscle (DM) presence and adherence to the standardised peri-procedural nine-items TURBT checklist was evaluated with logistic regression models. A Cox regression model was used to investigate the association of surgical experience with recurrence-free survival (RFS). RESULTS: A total of 503 patients were available for analysis. TURBT was performed by expert consultants in 265 (52.7%) patients, by young consultants in 149 (29.6%) and by residents in 89 (17.7%). Residents were more likely to have DM in the TURBT specimen than expert consultants (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.99, P = 0.04). Conversely, no differences in DM presence were seen between young vs expert consultants (OR 1.09, 95% CI 0.71-1.70, P = 0.69). The median checklist completion rate was higher for both residents and young consultants when compared to experts' counterparts (56% and 56% vs 44%, P = 0.009). When focusing on patients receiving a second-look TURBT, the persistent disease was associated with resident status (OR 4.24, 95% CI 1.14-17.70, P = 0.037) at initial TURBT. Surgical experience was not associated with 5-years RFS. CONCLUSION: Surgeon's experience in the case of adequate perioperative surgical checklist implementation was inversely associated with the presence of DM in the specimen but directly linked to higher probability of persistent disease at re-TURBT, although no 5-year RFS differences were noted.

• Klíčová slova
• #BladderCancer, #blcsm, #uroonc, bladder cancer, non-muscle-invasive bladder cancer, resident, surgical experience, transurethral resection of bladder tumour,
• MeSH
• cystektomie MeSH
• kontrolní seznam MeSH
• lidé MeSH
• nádory močového měchýře * chirurgie   patologie   MeSH
• prospektivní studie MeSH
• transuretrální resekce močového měchýře MeSH
• ukazatele kvality zdravotní péče MeSH
• urologie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node-positive (cN+) bladder cancer (BCa). OBJECTIVE: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. DESIGN SETTING AND PARTICIPANTS: This was an observational study of 369 patients with cT2-4 N1-3 M0 BCa. INTERVENTION: IC followed by consolidative radical cystectomy (RC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. RESULTS AND LIMITATIONS: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9-69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26-57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. CONCLUSIONS: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. PATIENT SUMMARY: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

• Klíčová slova
• Carboplatin, Induction chemotherapy, Oligometastatic, Survival, Urinary bladder neoplasms,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Although upper tract urothelial carcinoma (UTUC) is more common in the elderly, outcomes of neoadjuvant chemotherapy (NAC) in this population have never been explored. The objective of the study was to assess the impact of NAC on pathologic response and oncological outcomes stratified by age. PATIENTS AND METHODS: This multicenter study included 164 patients treated with NAC and radical nephroureterectomy (RNU) for clinically non-metastatic, high-risk UTUC. The cohort was stratified into two groups according to median age. Patients received either cisplatin-based or non-cisplatin-based chemotherapies. Pathologic responses were defined as pathologic objective response (pOR; ≤ ypT1N0) and pathologic complete response (pCR; ypT0N0). Univariable and multivariable logistic and Cox regression analyses were performed to identify predictors for pathologic response and survival outcomes. RESULTS: The cohorts' median age was 68 years with the elderly group (> 68 years) comprising 74 patients. Neoadjuvant chemotherapy included methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) in 66 (40%), gemcitabine cisplatin (GC) in 66 (40%) and non-cisplatin chemotherapy in 32 patients (20%). Younger patients received more often MVAC (50% vs. 28%) while elderly received more GC (34% vs. 47%) or non-cisplatin chemotherapy (16% vs. 24%) (P = .02). Overall, pOR and pCR were similar across age groups (52% vs. 47%; P = .5 and 10% vs. 8%; P = .7). While GC and non-cisplatin chemotherapy showed a lower pCR of 5% and 3%, respectively, MVAC revealed a pCR of 17% (P = .03) and was independently associated with a higher pCR (OR 4.31; P = .03). Kaplan-Meier analysis showed no difference in recurrence-free and cancer-specific survival, whereas a lower rate was seen in overall survival for the elderly. CONCLUSION: Elderly patients with high-risk UTUC eligible for cisplatin-based NAC prior to RNU may benefit from this multimodal therapy equally as their younger counterparts. Cisplatin-ineligible patients undergoing non-cisplatin-based NAC appeared to have lower response rates and should be considered for immediate RNU.

• Klíčová slova
• Age, Nephroureterectomy, Perioperative chemotherapy, Survival, Transitional cell carcinoma,
• MeSH
• cisplatina terapeutické užití   MeSH
• karcinom z přechodných buněk * patologie   MeSH
• lidé MeSH
• nádory močového měchýře * patologie   MeSH
• neoadjuvantní terapie škodlivé účinky   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• cisplatina MeSH

PURPOSE: We assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC) METHODS: In this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models. RESULTS: Overall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42-4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57-7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70-14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS. CONCLUSION: Preoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

• Klíčová slova
• Biomarker, Intermediate-risk, NMIBC, SII, Survival,
• MeSH
• hodnocení rizik MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře komplikace   imunologie   patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• zánět etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

This systematic review and meta-analysis aimed to assess and compare the perioperative and oncological outcomes of intracorporeal (ICUD) and extracorporeal (ECUD) urinary diversion following robot-assisted radical cystectomy (RARC). A systematic literature search of articles was performed in PubMed®, Web of Science®, and Scopus® databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. We included studies that compared patients who underwent RARC with ICUD to those with ECUD. Twelve studies including 3067 patients met the eligibility criteria. There were no significant differences between ICUD and ECUD in overall and major complications, regardless of the period (short-term [≤ 30 days] or mid-term [> 30 days]). Subgroup analyses demonstrated that ICUD performed by high-volume centers exhibited a significantly reduced risk of major complications (short-term: OR 0.57, 95% CI 0.37-0.86, p = 0.008, mid-term: OR 0.66, 95% CI 0.46-0.94, p = 0.02). Patients who underwent ICUD had lower estimated blood loss (MD -102.3 ml, 95% CI - 132.8 to - 71.8, p < 0.00001), less likely to receive blood transfusion rates (OR 0.36, 95% CI 0.20-0.62, p = 0.00003); and these findings were consistent in subgroup analyses by low-volume centers (MD-121.6 ml, 95% CI - 160.9 to - 82.3, p < 0.00001 and OR 0.36, 95% CI 0.20-0.62, p = 0.00003, respectively). ICUD had a higher lymph node yield (MD 3.68, 95% CI 0.80-6.56, p = 0.01). Patients receiving ICUD provided comparable complications, superior perioperative outcomes, and similar oncological outcomes compared with ECUD. Centralization of patients may contribute to a reduction of postoperative complications, while maintaining the advantages.

• Klíčová slova
• Complication, Extracorporeal urinary diversion, Hospital volume, Intracorporeal urinary diversion, Meta-analysis, Robot-assisted radical cystectomy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: TaG3 bladder cancer is an under-investigated disease and because of its rarity it is commonly studies together with T1G3 disease. We sought to exclusively study TaG3 disease and to determine the factors associated with disease progression. MATERIAL AND METHOD: We retrospectively studied patients with primary TaG3 bladder cancer. Progression to ≥pT1 and pT2 were analyzed using Cox and competing-risk regression analyses. RESULTS: Of 3,505 consecutive patients with nonmuscle invasive bladder cancer, 285 patients had primary TaG3 without concomitant carcinoma in-situ. Progression to ≥pT1 occurred in 21 patients (7.4%). In a multivariable competing-risk regression analysis, intravesical Bacillus Calmette-Guerin (BCG) was significantly associated with a lower risk of progression to ≥pT1 (HR 0.23, 95%CI 0.08-0.64, P = 0.005). Recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥pT1 (HR 7.81, 95%CI 2.50-24.44, P < 0.001). Progression to ≥T2 was observed in 9 patients (3.2%). In univariable competing-risk regression analyses, intravesical BCG was significantly associated with a lower risk of progression to ≥pT2 (HR 0.11, 95%CI 0.04-0.47, P = 0.003). On the other hand, recurrence in the first year of diagnosis was significantly associated with an increased risk of stage progression to ≥T2 (HR 7.12, 95%CI 1.50-33.77, P = 0.013). In a subgroup of 199 patients who were treated with BCG, there was no statistically significant association between tumor recurrence in the 1st year of diagnosis and stage progression to ≥pT1 (P = 0.14) or ≥pT2(P = 0.19). CONCLUSION: Patients with TaG3 bladder cancer are considered high risk but if appropriately treated with BCG that risk is considerably mitigated. Our data support that TaG3 without concomitant carcinoma in-situ should not be considered as aggressive as T1G3 as it has a lower risk of progression to muscle-invasive bladder cancer. Recurrence in the first year after diagnosis is the strongest predictor of progression to muscle-invasive bladder cancer.

• Klíčová slova
• Bladder cancer, NMIBC, TaG3, progression, recurrence,
• MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory močového měchýře patologie   MeSH
• progrese nemoci MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: The Plasminogen Activation System (PAS) plays a role in tumor growth, invasion and metastasis and has been associated with oncological outcomes in urinary bladder carcinoma (UBC). The use of the different components of this system as molecular markers could improve our understanding of the heterogeneous behavior of UBC and might enable earlier disease detection, individual risk stratification, more accurate outcome prediction and be a rationale for new targeted therapies. METHODS: A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database. RESULTS: The components of the PAS axis are involved in tumor progression through their signaling processes during angiogenesis, cell migration, metastasis and adhesion. The body of evidence shows an association of PAS component overexpression with adverse pathological features and clinical outcome in UBC. Overexpressed PAS components correlate with a higher pathological tumor grade and advanced tumor stage. In non-muscle-invasive bladder cancer (NMIBC), the PAS components were associated with disease outcome while in muscle-invasive bladder cancer (MIBC), it was associated with disease outcome and pathological features. Possible therapeutic approaches in the PAS for the treatment of UBC have only been sparsely investigated in in vitro and in vivo studies. Intravesical plasminogen activator inhibitor 1 (PAI-1) instillation in animal models yielded interesting results and warrant further exploration in Phase II studies. CONCLUSION: The overexpression of PAS components in UBC tumor tissue is associated with adverse pathological features and worse oncological outcomes. These findings are mainly based on preclinical studies and retrospective series, which requires further prospective studies to translate the PAS into clinically useful biomarkers and therapeutic targets.

• Klíčová slova
• PAI, review, therapy, uPA, uPAR, urothelial cancer,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: To compare oncological outcomes of open (ORNU) and laparoscopic radical nephroureterectomy (LRNU) after controlling for preoperative patient-derived factors. PATIENTS AND METHODS: We evaluated a multi-institutional collaborative database composed of 3984 patients diagnosed with upper tract urothelial carcinoma (UTUC) treated with RNU between 2006 and 2018. To adjust for potential selection bias, propensity score matching adjusted for age, gender and American society Anesthesiology (ASA) score was performed with one ORNU patient matched to one LRNU patient. Uni- and multivariable Cox regression evaluating the risk of overall recurrence, cancer-specific mortality (CSM) and overall mortality (OM) in the overall population and after propensity matching were performed. RESULTS: In total, 3984 patients underwent RNU, of these 3227 (81%) patients were treated with ORNU and 757 (19%) patients with LRNU. Within a median follow-up of 62 months, 1276 recurrences, 844 CSMs and 1128 OMs were recorded. On multivariable analyses, the LRNU approach was associated with an increased risk of overall recurrence (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.03-1.54; P = 0.02), but on the other hand LRNU was associated with a protective effect on CSM (HR 0.74, 95% CI 0.56-0.98; P = 0.04). After propensity matching analyses adjusted for age, gender and ASA score, 757 patients treated with LRNU and 757 patients treated with ORNU were available for the analyses. On multivariable Cox regression, LRNU vs ORNU was not associated with any difference in overall recurrence (P = 0.08), CSM (P = 0.1) or OM (P = 0.9). CONCLUSION: Our present data suggest that even if the type of approach to RNU was associated with different survival outcomes considering the overall population, this difference vanished when adjusted for potential confounders in propensity matching analyses. Therefore, we found that LRNU is not inferior to the ORNU approach for the treatment of UTUC. ABBREVIATIONS: ASA: American Society of Anesthesiology; CIS: carcinoma in situ; CSM: cancer-specific mortality; HR: hazard ratio; IQR: interquartile range; LN: lymph node; LNI: lymph node invasion; LVI: lymphovascular invasion; OM: overall mortality; pT: pathological tumour stage; RCT: randomised controlled trial; (L)(O)RNU: (laparoscopic) (open) radical nephroureterectomy; UTUC: upper tract urothelial carcinoma.

• Klíčová slova
• RNU, UTUC, Upper tract urothelial carcinoma, laparoscopic, open, radical nephroureterectomy,
• Publikační typ
• časopisecké články MeSH