The importance of second-look ureteroscopy implementation in the conservative management of upper tract urothelial carcinoma.

PURPOSE: The purpose of the study was to evaluate the effect of second-look ureteroscopy (SU) in the endoscopic operative work-up of patients with upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Patients with UTUC who underwent SU between 2016 and 2021 were included. Cancer detection rate (CDR) at SU was defined as endoscopic visualization of tumor. The effect of SU on recurrence-free survival (RFS), radical nephroureterectomy-free survival (RNU-FS), bladder cancer-free survival (BC-FS), and cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. Multivariate logistic regression analysis (MLR) assessed predictors of negative SU. Finally, we evaluated the effect of SU timing on oncological outcomes, classifying SUs as "early" (≤ 8 weeks) and "late" (> 8 weeks). RESULTS: Overall, 85 patients underwent SU. The CDR at SU was 44.7%. After a median follow-up was 35 (IQR: 15-56) months, patients with positive SU had a higher rate of UTUC recurrence (47.4% vs 19.1%, p = 0.01) and were more frequently radically treated (34.2% vs 8.5%, p = 0.007). Patients with high-grade disease (hazard ratio [HR]: 3.14, 95% CI 1.18-8.31; p = 0.02) had a higher risk of UTUC recurrence, while high-grade tumor (HR: 3.87, 95%CI 1.08-13.77; p = 0.04) and positive SU (HR: 4.56, 95%CI 1.05-22.81; p = 0.04) were both predictors of RNU. Low-grade tumors [odds ratio (OR): 5.26, 95%CI 1.81-17.07, p = 0.003] and tumor dimension < 20 mm (OR: 5.69, 95%CI 1.48-28.31, p = 0.01) were predictors of negative SU. Finally, no significant difference emerged regarding UTUC recurrence, RNU, BC-FS, and CSM between early vs. late SUs (all p > 0.05). CONCLUSIONS: SU may help in identifying patients with UTUC experiencing an early recurrence after conservative treatment. Patients with low-grade and small tumors are those in which SU could be safely postponed after 8 weeks.

The Role of Surgery in Local Recurrences after Radical Cystectomy for Bladder Cancer.

INTRODUCTION: Local recurrence (LR) after radical cystectomy (RC) for bladder cancer has a bad prognosis. Treatment options include chemotherapy, radiation therapy and surgical excision, but few data is available on the advantages of surgery for these patients. PATIENTS AND METHODS: We evaluated our series of 8 selected patients who underwent surgery for locally recurrent bladder cancer after RC. RESULTS: The median time to recurrence after cystectomy was 20.8 months. The complications rate and severity were not negligible. Pathology report confirmed urothelial carcinoma with negative margins in all patients. After LR treatment, 4 patients recurred locally for a second time and 3 developed distant metastasis. They all died after a median follow-up of 10.4 months. One patient remained disease free after 14 months. CONCLUSIONS: The prognosis of patients with LR is poor regardless of surgical treatment and reflects the aggressive biological nature of urothelial tumors.

[Economic features of active surveillance]. / Aspectos economicos de la vigilancia activa.

In a context where there is evidence that not every patient with low risk prostate cancer needs to be treated from the start, active treatments are expensive and public health care systems need to save money, studies on cost-effectiveness are a priority. To elaborate this article, we reviewed the publications on cost and cost-effectiveness of localized prostate cancer treatments that include active surveillance. In patients with low risk localized prostate cancer active surveillance is more cost-effective than active treatment. With time active surveillance may be more expensive than brachytherapy or radical prostatectomy. The frequency of prostatic biopsies and the percentage of conversions to active treatment will be determinant in final costs of active surveillance.

Robotic kidney transplantation.

Kidney transplantation is the best treatment option for patients with end-stage renal disease owing to improved survival and quality of life compared with dialysis. The surgical approach to kidney transplantation has been somewhat stagnant in the past 50 years, with the open approach being the only available option. In this scenario, evidence of reduced surgery-related morbidity after the introduction of robotics into several surgical fields has induced surgeons to consider robot-assisted kidney transplantation (RAKT) as an alternative approach to these fragile and immunocompromised patients. Since 2014, when the RAKT technique was standardized thanks to the pioneering collaboration between the Vattikuti Urology Institute and the Medanta hospital (Vattikuti Urology Institute-Medanta), several centres worldwide implemented RAKT programmes, providing interesting results regarding the safety and feasibility of this procedure. However, RAKT is still considered an alternative procedure to be offered mainly in the living donor setting, owing to various possible drawbacks such as prolonged rewarming time, demanding learning curve, and difficulties in carrying out this procedure in challenging scenarios (such as patients with obesity, severe atherosclerosis of the iliac vessels, deceased donor setting, or paediatric recipients). Nevertheless, the refinement of robotic platforms through the implementation of novel technologies as well as the encouraging results from multicentre collaborations under the umbrella of the European Association of Urology Robotic Urology Section are currently expanding the boundaries of RAKT, making this surgical procedure a real alternative to the open approach.

Sequential Treatment With Bacillus Calmette-Güerin (BCG) and Mitomycin C Administered With Electromotive Drug Administration (EMDA) in Patients With High-Risk Nonmuscle Invasive Bladder Cancer After BCG Failure.

BACKGROUND: Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed. OBJECTIVES: To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. MATERIAL AND METHODS: We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC + EMDA, BCG, BCG, MMC + EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. RESULTS: Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. CONCLUSION: Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases.

Long-Term Oncologic Outcomes of Endoscopic Management of High-Risk Upper Tract Urothelial Carcinoma: The Fundació Puigvert's Experience.

Objectives: Many patients with upper tract urothelial carcinoma (UTUC) outside of the low-risk criteria may possess low absolute risks of distant progression. Herein, we hypothesized that careful selection of high-risk patients undergoing an endoscopic approach could result in acceptable oncologic outcomes. Materials and Methods: Patients with high-risk UTUC managed endoscopically between 2015 and 2021 were retrospectively identified from a prospectively maintained single academic institution database. Elective and imperative indications for endoscopic treatment were considered. Regarding elective indications, the decision to perform endoscopic treatment was systematically proposed to high-risk patients in whom macroscopically complete ablation was deemed feasible, excluding invasive appearance on CT scan, and without histologic variant. Results: A total of 60 patients with high-risk UTUC met our inclusion criteria (29 imperative and 31 elective indications). The median follow-up in patients without any event was 36 months. At 5 years, the estimated overall survival, cancer-specific survival, metastasis-free survival, UTUC recurrence-free survival, radical nephroureterectomy-free survival, and bladder recurrence-free survival were 57% (41-79), 75% (57-99), 86% (71-100), 56% (40-76), 81% (70-93), and 69% (54-88), respectively. All oncologic outcomes were similar between patients with elective and imperative indications (all log-rank p > 0.05). Conclusions: In conclusion, we report the first large series of endoscopic treatment in patients with high-risk UTUC, arguing that promising oncologic outcomes can be achieved in properly selected candidates. We encourage multi-institutional collaborative work as a large cohort of high-risk patients treated endoscopically may allow subgroup analyses to define the best candidates.

Oncological and Renal Function Outcomes in Patients Who Underwent Simultaneous Radical Cystectomy and Nephroureterectomy for Synchronous or Metachronous Panurothelial Carcinoma.

OBJECTIVE: To assess clinical outcomes of patients who underwent simultaneous radical cystectomy (RC) and radical nephroureterectomy (RNU) for panurothelial carcinoma (PanUC). MATERIALS AND METHODS: A retrospective analysis of 67 patients who underwent simultaneous RC and unilateral RNU for PanUC, from 1996 to 2017. Kaplan-Meier estimates for remnant urothelium recurrence-free survival, metastasis-free survival, overall survival (OS), and cancer-specific survival (CSS) were performed. Cox multivariate models were constructed. RESULTS: The median follow-up was 38 months, 29.8% of patients had a recurrence, 34.3% had metastasis, 67.2% of patients died from any cause, and 37.3% died from urothelial carcinoma. Overall survival and CSS rates at 5 years were 44% and 61%, respectively. In multivariate analysis, progression to muscle-invasive bladder cancer before surgery, presence of muscle-invasive stages at RC and/or RNU, and prostatic urethra involvement were predictors for worse metastasis-free survival and CSS. Forty-one patients (61.2%) had an estimated glomerular filtration rate (eGFR) <60 mL/min before surgery and the number rose to 56 (83.5%) after surgery; 29.8% patients needed renal function replacement therapy after surgery (16 haemodialysis and 4 renal transplant). CONCLUSION: Patients with PanUC who undergo simultaneous surgery have adverse oncological (only 4 out of every 10 remain alive at 5 years) and functional outcomes (1 out of 3 will need renal function replacement therapy after surgery). Up to a third of the patients had a recurrence (urethra or contralateral kidney) within 18 months, justifying close surveillance or considering prophylactic urethrectomy. These data should help in counsel on morbidity and life expectancy.

Long-term Recurrence and Progression Patterns in a Contemporary Series of Patients with Carcinoma In Situ of the Bladder With or Without Associated Ta/T1 Disease Treated with Bacillus Calmette-Guérin: Implications for Risk-adapted Follow-up.

BACKGROUND: Limited data are available on patients with carcinoma in situ (CIS) of the bladder managed according to current clinical practice guidelines. OBJECTIVE: To assess the patterns of recurrence, progression to muscle-invasive bladder cancer (MIBC), and upper tract urothelial carcinoma (UTUC) in patients with CIS, and to compare the effectiveness of adequate versus inadequate bacillus Calmette-Guérin (BCG) immunotherapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 386 patients with CIS of the bladder with or without associated pTa/pT1 disease treated with BCG between 2008 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier estimations and an inverse probability of treatment weighting (IPTW)-Cox regression were performed to compare recurrence-free survival (RFS) and progression-free survival (PFS) and UTUC incidence over time for patients who received adequate versus inadequate BCG treatment. RESULTS AND LIMITATIONS: The median follow-up was 70.5 mo. At 5 and 10 yr, RFS was 82% and 52%, PFS was 93.6% and 75.8%, and UTUC incidence was 1.7% and 2.9%, respectively. Most recurrence (73.6%) and progression (69.1%) events occurred in the first 3 yr of follow-up, while 38.7% of UTUC incident events were recorded after 5 yr of follow-up. IPTW-Cox regression revealed that patients who received BCG treatment had a lower risk of recurrence (hazard ratio [HR] 0.21, 95% confidence interval [CI] 0.13-0.34), progression (HR 0.46, 95% CI 0.25-0.87), and UTUC incidence (HR 0.24, 95% CI 0.09-0.64). Limitations include the retrospective design and potential selection bias. CONCLUSIONS: Patients with CIS of the bladder show a high risk of recurrence, progression, and UTUC incidence. Most of these outcomes occur during the first 3 yr of follow-up, but a significant proportion of the events occur at long-term follow-up. Although receipt of adequate BCG treatment improves outcomes, intensive and long-term surveillance may be warranted. PATIENT SUMMARY: We investigated the long-term cancer control outcomes for patients with carcinoma in situ (CIS; cancerous cells that have not spread from where they first formed) of the bladder. Patients with CIS have a high risk of cancer recurrence and progression. Treatment with bacillus Calmette-Guérin (BCG) improves outcomes.

Second to fourth digit ratio, adult testosterone level and testosterone deficiency.

OBJECTIVES: The ratio of the second and fourth finger lengths (2D/4D) is related to intrauterine exposure to testosterone. The relationship between 2D/4D and adult hormonal pattern is controversial. The aim of our study was to determine if there was a relationship between adult serum testosterone levels and the 2D/4D ratio. PATIENTS AND METHODS: We prospectively recruited 204 consecutive patients referred for transrectal prostate biopsy between January 2008 and June 2009. The same physician performed clinical examinations, 2D/4D measurements and the transrectal biopsy in all cases. Cut-off points of 231 and 346 ng/dL testosterone (8 and 12 nmol/L) were used. 2D/4D determination was done with a vernier calliper on the left hand. The hormonal profile (testosterone and sexual hormone binding globulin) of the patients was determined between 7.00 am and 11.00 am. Age, weight, height, body mass index, toxic habits, digital rectal examination, prostate-specific antigen and 2D and 4D measurements were recorded prospectively. RESULTS: The mean age was 67 ± 7 years and the mean testosterone level was 413 ± 18 ng/dL (14.33 ± 0.62 nmol/L). The percentages of patients with testosterone <231 ng/dL (8 nmol/L) and testosterone <346 ng/dL (12 nmol/L) were 6.1 and 30.6 respectively. Univariate analysis showed that low 2D/4D ratios were related to higher levels of testosterone (B=-741.98; ß=-0.165, P= 0.045) and also with low prevalence of biochemical hypogonadism (testosterone <346 ng/dL). Mean 2D/4D ratio in patients with testosterone >346 ng/dL was lower than in patients with testosterone <346 ng/dL (2D/4D 0.97 ± 0.037 vs 0.99 ± 0.043 depending on their hormonal status, P= 0.05). High 2D/4D ratio was associated with low testosterone serum levels (P= 0.046). CONCLUSIONS: The 2D/4D ratio is related to adult testosterone levels and the presence of testosterone deficiency syndrome. Patients with high 2D/4D ratios have lower testosterone levels and higher risk of testosterone deficiency syndrome.

Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment.

UNLABELLED: What's known on the subject? and What does the study add? Prostate growth is ruled by testosterone. Nevertheless, the paradigm that high testosterone levels induce prostate cancer development or lead to a poor prognosis in prostate cancer is not supported by evidence. A growing number of studies suggest that, on the contrary, low testosterone levels are related to poor prognosis features in prostate cancer such as higher prostate-specific antigen or higher Gleason score. Our experience shows that testosterone levels are related to risk of progression of prostate cancer - those men with lower testosterone levels are at higher risk of progression of their prostate cancer after treatment delivery. OBJECTIVES: • Low testosterone levels have been related to a higher diagnosis of prostate cancer (PCa). Hormonal levels have been related to poor prognosis factors in men with PCa, mainly after radical prostatectomy. • Our aim was to determine the relationship between hormonal levels and PCa prognosis factors in men with PCa prior to the onset of treatment. PATIENTS AND METHODS: • We prospectively analysed 137 males diagnosed in our centre with PCa with 5+5 core prostate biopsies from February 2007 to December 2009. • As part of our clinical protocol, we performed hormonal determination (testosterone and sex hormone binding globulin) following International Society of Andrology, International Society for the Study of the Aging Male and European Association of Urology recommendations. • Free testosterone and bioavailable testosterone were calculated using Vermeulen's formula. • Age, prostate-specific antigen (PSA), free to total PSA, PSA density, number of previous biopsies, digital rectal examination staging, Gleason score, percentage of tumour in the biopsy sample, bilaterality of the tumour and risk of progression group were prospectively recorded. RESULTS: • Higher testosterone levels were related to lower digital rectal examination staging (P= 0.02) and lower PSA level (P= 0.05). Higher testosterone was not related to lower Gleason score (P= 0.08). • Testosterone was inversely related to PCa bilaterality (P < 0.01) and percentage of tumour in the biopsy (P < 0.01). • High testosterone levels were found in patients allocated to the low risk of progression group and inversely (P= 0.03). • In multivariate analysis, higher age and lower testosterone were related to higher D'Amico risk of progression. CONCLUSION: • Patients with PCa and lower testosterone levels have poor prognosis factors and higher tumour burden before treatment onset. These findings reinforce the idea that low testosterone levels pretreatment are related to a poor prognosis in PCa.

Low testosterone level predicts prostate cancer in re-biopsy in patients with high grade prostatic intraepithelial neoplasia.

UNLABELLED: What's known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia (HGPIN) is a risk factor for prostate cancer (PCa), but only multifocality is an indication for early rebiopsy. Other risk factors for PCa development from HGPIN remain unknown. PCa is related to testosterone. Testosterone has been proven to be linked to PCa detection and poor prognosis PCa. This study shows that low free and bioavailable testosterone levels are associated with an increased risk of PCa in a rebiopsy after HGPIN diagnosis. Men with low testosterone levels and HGPIN could therefore be considered a high-risk cohort for developing PCa. OBJECTIVE: To determine the relevance of the hormonal profile of patients with high grade prostatic intraepithelial neoplasia (HGPIN) and its relationship to prostate cancer (PCa) in rebiopsy. PATIENTS AND METHODS: We prospectively analysed 82 consecutive patients with a diagnosis of HGPIN without PCa in a prostate biopsy between September 2007 and December 2009. Of these 82 patients, 45 underwent rebiopsy and their hormonal profile was determined (testosterone and sex hormone-binding globulin [SHBG]) as part of our clinical protocol. Patient age, PSA level, prostate volume, PSA density, testosterone, free testosterone, bioavailable testosterone and SHBG were recorded prospectively. A comparative study between those patients with a positive rebiopsy and those with a negative rebiopsy was performed. RESULTS: We found that free testosterone (P = 0.04), bioavailable testosterone (P = 0.04) and SHBG (P = 0.02) were significantly associated with a positive rebiopsy. Other variables such as age (P = 0.745), PSA level (P = 0.630), prostate volume (P = 0.690), PSA density (P = 0.950), testosterone (P = 0.981) and prostatic intraepithelial neoplasia multifocality (P = 0.777) were not associated with the presence of adenocarcinoma in the rebiopsy. CONCLUSIONS: Patients with adenocarcinoma of the prostate after a diagnosis of HGPIN have higher SHBG levels and lower calculated free testosterone levels than patients with a negative rebiopsy. Testosterone levels might be a useful indication for rebiopsy after HGPIN diagnosis.

Low testosterone bioavailability is related to prostate cancer diagnose in patients submitted to prostate biopsy.

INTRODUCTION: Relationship between prostate cancer (PCa) and testosterone (T) is controversial. Conflicting evidence has been published about T levels and development of PCa. AIM: (1) To determine the relationship between hormone levels and the diagnosis of PCa. (2) To specifically focus on the relationship between PCa and T in men classified as biochemically hypogonadal. MATERIALS AND METHODS: Prospective analysis of 1,000 transrectal ultrasound guided prostate biopsies (5 + 5 cores biopsies) between September 2007 and January 2010 in one center. Indication for prostate biopsy was suspicion of PCa on the basis of elevated prostate-specific antigen (PSA) and/or digital rectal examination (DRE). Serum testosterone and sex hormones binding globulin (SHBG) were determined in these patients. Of 557 men, the data were sufficient for further analysis. Age, body mass index (BMI), smoking/drinking habits, PSA, free PSA, PSA density, prostate volume, number of previous biopsies, DRE, and hormone levels were prospectively recorded. RESULTS: No relationship was found between T and PCa (449 ± 167 ng/dL in PCa versus 437 ± 169 ng/dL in non-PCa). SHBG was significantly higher in patients with PCa (51 ± 27 ng/dL in PCa vs. 44 ± 18 ng/dL in non-PCa). In hypogonadal men, T levels correlated with the PCa (235 ± 95 ng/dL in men with PCa versus 270 ± 58 ng/dL in men without PCa, P = 0.004). CONCLUSIONS: T levels were comparable in men with and without PCa, but SHBG levels were significantly higher in men with PCa. In men with low T, the men with PCa had a lower serum T levels and a lower prostate volume than the men without PCa.

Transitional cell carcinoma of the upper urinary tract after cystectomy.

OBJECTIVE: To assess the incidence, characteristics and outcome of upper urinary tract tumors (UUTTs) that developed in patients who underwent radical cystectomy for urothelial carcinoma. METHODS: We performed an analysis of original and review articles that were related to post-cystectomy UUTTs. The articles were published from 1984 through 2011 and were identified by searching the Pub Med database. RESULTS: The incidence of post-cystectomy UUTT ranges from 2-6% and is stable over time. The primary risk factors include a tumor in the distal ureter in the cystectomy specimen and signs of multifocal disease (e.g., multiplicity, a history of non-muscle-invasive bladder tumor, diffuse carcinoma in situ and the presence of a tumor in the prostatic urethra). The median time between cystectomy and UUTT exceeded three years in 70% of the reviewed cases. Even with regular radiological follow-up visits, over 50% of cases were diagnosed after clinical onset, and over 70% were in an advanced stage. Currently, a multidetector computed tomography urography is the standard technique for studying the upper urinary tract. In patients with urinary diversion, the maximum yield of cytology can be obtained when this technique is used to confirm a clinical or radiological suspicion of UUTT. Nephroureterectomy is the treatment of choice for these tumors. The high prevalence of high-grade and stage UUTT results in endourological treatment being restricted to only selected cases. Despite surgery, fewer than 30% of post-cystectomy UUTT patients experience prolonged survival. CONCLUSIONS: Post-cystectomy UUTT is rare and usually has a late onset. A distal ureteral tumor and the presence of multifocal disease are its primary risk factors. Most cases of post-cystectomy UUTT are diagnosed clinically and in advanced stages.

Higher second fourth digit ratio predicts higher incidence of prostate cancer in prostate biopsy.

OBJECTIVES: To analyze the validity of the ratio between the second and fourth finger (digit ratio; 2D/4D) of the left hand as a predictor for prostate cancer (PCa) in a group of men undergoing prostate biopsy. METHODS: We prospectively recruited 204 consecutive patients referred for transrectal prostate biopsy due to PSA elevation or abnormal digital rectal examination between January 2008 and June 2009. The same physician performed all clinical examinations, digit ratio measurements and transrectal biopsy in all cases. Digit ratio determination was done with a Vernier caliper in the left hand. Patients underwent determination of hormone profile (testosterone and sexual hormone binding globulin (SHBG)) between 7:00AM and 11:00AM. Age, digital rectal examination, PSA, free PSA, PSA density, testosterone and SHBG, pathological report and D2 and D4 measurements were recorded prospectively. RESULTS: Variables age and SHBG were directly related to PCa. Prostate volume was inversely related to neoplasia. 2D/4D ratio >0,95 (OR (CI 95%) 4,4 (1,491-13,107) was related to neoplasia. No differences in PCa were seen regarding PSA, free PSA, PSA density, digital rectal examination and testosterone. CONCLUSION: High digit ratio predicts PCa in men undergoing prostate biopsy. Digit ratio >0,95 has 4-fold risk of PCa compared to men with digit ratio ≤0.95.

Impact of clinical and pathological subtypes of carcinoma in situ (CIS) of the bladder: Lessons learned from long-term follow-up of a series of CIS patients treated with BCG.

OBJECTIVE: Some attempts have previously been made to stratify patients with CIS for the purpose of risk-adapted clinical management and clinical trial design. In particular, two classification systems have been proposed: clinical classification, comprising primary (P-CIS), concomitant (C-CIS), and secondary (S-CIS) disease, and pathological classification, comprising P-CIS, cTa-CIS, and cT1-CIS. The aim of the present study was to assess the impact of both classifications on BCG response, recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS). PATIENTS AND METHODS: We performed a retrospective analysis of 386 patients with bladder CIS, with or without associated cTa/cT1 disease, treated with BCG instillations between 2008 and 2015. Patients were stratified according to the two classification systems. Cox multivariate regression models were used to assess the impact of these subtypes on BCG response, RFS, PFS, OS, and CSS. We also performed a cumulative meta-analysis according to PRISMA guidelines. RESULTS: The median follow-up was 70.5 months. According to the clinical classification, 34 (8.8%) patients had P-CIS, 81 (21%) S-CIS, and 271 (70.2%) C-CIS. The pathological classification showed 34 (8.8%) patients to have P-CIS, 190 (49.2%) cTa-CIS, and 162 (42%) cT1-CIS. In the overall cohort, BCG response was reported in 296 (76.7%); 159 (41.2%) had recurrence, 55 (14.2%) had progression, and 67 (17.4%) underwent radical cystectomy. Death from any cause was recorded in 135 (35%) and death from urothelial carcinoma in 38 (9.9%). Cox multivariate regression analysis showed that neither clinical classification nor pathological classification is an independent predictive factor for BCG response, RFS, PFS, OS, or CSS after adjusting for confounders. In the pooled meta-analysis, two studies and the present series were included for evidence synthesis, recruiting a total of 941 patients. We found no statistically significant difference across the groups for both classifications with respect to BCG response, RFS, PFS, and CSS. CONCLUSIONS: Currently, the supporting evidence for an impact of clinical classification and pathological classification on oncological outcomes of CIS of the bladder is insufficient to justify their use to guide clinical management or follow-up.

Recommendations for living donor kidney transplantation.

This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.

Can we identify those patients who will benefit from prostate-sparing surgery? Predictive factors for invasive prostatic involvement by transitional cell carcinoma.

OBJECTIVES: To determine which patients may benefit from prostate-sparing surgery and which factors are predictive of invasive prostatic involvement. MATERIALS AND METHODS: A total of 717 men underwent radical cystoprostatectomy (RC) for bladder transitional cell carcinoma (TCC) between 1978 and 2002. Analysis of prostatic urethral involvement by transitional cell carcinoma (pTCC) and of invasive prostatic involvement by TCC was performed according to recurrence, presence of carcinoma in situ (CIS) and multifocality, previous intravesical chemotherapy, grade, stage and location of bladder tumor, presence of CIS in precystectomy transurethral resection (TUR) and indication for RC. RESULTS: pTCC was present in specimens from 140 patients (19.5%), of whom 83 (59.3%) showed invasive prostatic involvement. Tumor location at the trigone or bladder neck (p = 0.011, OR 2.29, 95% CI 1.21-4.33) and a history of CIS (p = 0.003, OR 2.03, 95% CI 1.27-3.22) were independent predictors of pTCC. Presence of a solitary T2-T3 bladder tumor was a predictive factor for invasive prostatic involvement (p = 0.001, OR 3.73, 95% CI 1.70-8.16). Neither solitary tumors nor T2-T3 bladder tumors showed significant differences in 5 year specific survival (p = 0.277 and p = 0.618 respectively) when comparing patients according to the presence of superficial or invasive prostatic involvement. Bladder tumor stage in precystectomy TUR was a predictor of disease-specific survival (p = 0.018, OR 1.62, 95% CI 1.08-2.44). CONCLUSIONS: Patients with a history of CIS and bladder tumor location at the trigone or bladder neck are not candidates for prostate-sparing surgery. The only variables that can predict invasive prostatic involvement are the presence of a solitary T2-T3 bladder tumor at the trigone or bladder neck.

Outcomes following surgical management of adrenocortical carcinoma: A single-center experience. / Resultados del manejo quirúrgico del carcinoma adrenocortical: experiencia de un centro hospitalario.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare and heterogeneous disease, with challenging management and poor prognosis. Surgery withcurative intent is the preferred treatment option for localized disease, with a reported 5-year survival rate of 55% for complete resections. However, owing to the high risk of recurrence there is a need for adjuvant therapies, such as mitotane, an adrenolytic drug, or irradiation, while in advanced disease the standard of careis a combined chemotherapy scheme. The aim of this study was to report our experience in the surgical management and outcomes of ACC patients. MATERIALS AND METHODS: A retrospective observational study was performed in a cohort of ACC patients who had undergone surgical resection (open or laparoscopic approach) and were followed up at our tertiary hospital. Patients with localized or locally advanced disease were included in the analysis. All medical records, including clinical, surgical, pathologic, and follow-updata, were collected and analyzed. RESULTS: A total of 19 ACC patients were managed at our center between August 1990 and August 2013. The median age at diagnosis was 50.5 years (range 19-72), and most patients were males. Abdominal pain was the most common clinical presentation (n=9,47.4%). Abdominal contrast-enhanced computed tomography (CT) was performed in all cases. Only 3 tumors (15.8%) were functional and most were stage II at diagnosis (n=9, 47.4%). No patient presented metastasis. Of the 19 patients, 18 (94.7%) under went surgerywith curative intent, while one (5.3%) received adjuvant radiotherapy (ART). The open approach was used in 17 patients (89.5%), while the remaining 2 (10.5%) underwent laparoscopy. Postoperative complications occurred in 8 patients (42.1%); none were of grade IV or V. Median follow-up was 66 months (range 3-312). The majority of patients (n=15, 78.9%) were disease free with surgery alone. None received adjuvant mitotane therapy (AMT). Four patients (21%) experienced metachronous metastases and 3 (15.8%) local recurrence after a median time of 10.5 months (range 2-60) and 9.3 months (range 1.5-30), respectively. The 5-year overall survival rate was 47.4%. CONCLUSIONS: Our findings confirm both the unpredictable nature of ACC and the accepted primary role of surgery. The use of adjuvant therapy was less frequent in this series than is supported currently. However, a multidiscipinary approach should be the initial step in the management of this rare malignancy.

OBJETIVO: El carcinoma adrenocortical es una enfermedad heterogénea y rara que conlleva un manejo complicado y cuyo pronóstico es malo. Ante una enefermedad localizada el manejo quirúrgico es de elección, observando una tasa de supervivencia a los 5 años del 55% en resecciones completas. Sin embargo, debido a la alta tasa de recurrencias, se requiere complementar el manejo con una terapia adyuvante como es el caso del mitotane, un agente adrenolítico, o la radioterapia. En casos de enfermedad avanzada la terapia de elección incluye una pauta de quimioterapia combinada. El objetivo del presente estudio es reportar nuestra experiencia en el manejo quirúrgico y resultados obtenidos de los pacientes con diagnóstico de carcinoma adrenocortical. MATERIALES Y MÉTODOS: Se realizó un estudio observacional de una cohorte de pacientes diagnosticados de carconinoma adrenocortical que requirieron un manejo quirúrgico (abierto o laparoscópico) y que realizaron su seguimiento en nuestro hospital terciario. Se incluyó a pacientes con enfermedad localizada y localmente avanzada en el análisis. Todos los dados clínicos, quirúrgicos, patológicos y de seguimiento fueron recolectados para el análisis. RESULTADOS: Entre agosto del 1990 y agosto del 2013 un total de 19 pacientes diagnosticados de carcinoma adrenocortical fueron tratados en nuestro centro. La mediana de edad al diagnóstico fue 50,5 años (rango 19-72), siendo la mayoría hombres. El síntoma inicial mas frecuente fue el dolor abdominal (n=9, 47,4%). Una tomografía computarizada con contraste fue realizada en todos los casos. Sólo 3 tumores (15,8%) eran funcionales y la mayoría correspondía a un estadio II al diagnóstico (n=9, 47,4%). Ningún paciente presentaba metástasis. De los 19 pacientes,18 (94,7%) requirieron cirugía con intención curativa, mientras que a uno (5,3%) se le realizó radioterapia adyuvante. El abordaje abierto se usó en 17 pacientes (89,5%), mientras que a 2 pacientes (10,5%) se les realizó una técnica laparoscópica. Complicaciones postquirúrgicas ocurrieron en 8 pacientes (42,1%), de las cuales ninguna fue de grado IV o V. La mediana de seguimiento fue de 66 meses (rango 3-312). La mayoría de los pacientes (n=15, 78,9%) permanecieron libres de enfermedad únicamente con un manejo quirúrgico. Ninguno recibió terapia adyuvante con mitotane. Cuatro pacientes (21%) presentaron metástasis metacrónicas y 3 (15,8%) recurrencia local tras una mediana de tiempo de 10,5 meses (rango 2-60) y 9,3 meses (rango1,5-30), respectivamente. La tasa de supervivencia globala los 5 años fue del 47,4%. CONCLUSIONES: Nuestros resultados confirman tanto la naturaleza impredecible del carcinoma adrenocortical como la aceptación del rol primario de la cirugía en su manejo. El uso de un agente adyuvante fue menos frecuente en esta serie respecto a lo respaldado actualmente. Sin embargo, un manejo multidisciplinar debería ser el primer paso a seguir en el tratamiento de esta rara enfermedad.

Endoscopic exploration directly impacts clinical decision making in the management of patients with suspected upper tract urothelial carcinoma following radical cystectomy.

OBJECTIVES: To assess whether the use of endoscopic exploration (EE) as a routine diagnostic tool in patients with clinical suspicion of upper tract urothelial carcinoma (UTUC) following radical cystectomy (RC) significantly impacts management decision-making and to describe the oncological outcomes of patients with UTUC after RC. MATERIALS AND METHODS: We performed a retrospective review of medical records of patients with suspicion of UTUC after RC between 2000 and 2019. Patient demographics, clinicopathological features, treatments, and outcomes were analyzed. RESULTS: We identified 60 patients with suspicion of UTUC. After diagnostic work-up, 16 were submitted to radical nephroureterectomy (RNU) and 44 underwent diagnostic EE. After EE, a further 18/44 (40.9%) were submitted to RNU, while no evidence of tumor was found in 12 (27.3%) and the remaining 12 (27.3%) underwent endoscopic treatment (ET). Thus, in 24/44 (54.5%) patients the primary treatment strategy, i.e., RNU, was altered. Twenty-nine (85.3%) of the 34 patients who underwent RNU had high-grade tumors and 16 (47%) had the muscle-invasive disease. In the ET group, 6 (50%) had high-grade tumors and 10 (83.4%) had tumors less than 2 cm. The 5-year estimated recurrence-free survival and cancer-specific survival were, respectively, 58.4% and 45.6% in the RNU group and 25% and 80.8% in the ET group. CONCLUSION: EE significantly impacts clinical decision-making in patients with suspicion of UTUC after RC, resulting in a change in treatment strategy in approximately half of the patients. UTUC following RC has a poor prognosis and although RNU is the gold standard, ET could be considered in a selected group of patients.

Comparison of standard vs. palliative management for bladder cancer in patients older than 85 years: multicenter study of 317 de novo tumors.

BACKGROUND: The peak incidence of bladder cancer (BCa) occurs at 85 years but data on treatment and outcome are sparse in this age group. We aimed to compare the outcomes of high-grade nonmuscle invasive BCa (HG NMIBC) and muscle invasive BCa (MIBC) treated with standard therapies vs. palliative management in patients >85 years. METHODS: Retrospective multicenter study of 317 patients >85 years who underwent transurethral resection (TURB) for de novo BCa between 2014 and 2016. Standard management consisted in following EAU-guidelines and palliative in monitoring patients without applying oncological treatments after TURB. Low-grade tumors were not compared because all of them were considered to have followed a standard management. RESULTS: Median age was 87 years (85-97). ASA-score was as follows: II, 34.7%; III, 52.1%; IV, 13.2%. Pathological examination showed: 86 Low-grade NMIBC (27.1%), 156 HG NMIBC (49.2%), and 75 MIBC (23.7%). Median follow-up of the series was 21 months (3-61) and median overall survival (OS) 29 (24-33). Among HG NMIBC, 77 patients (49.4%) received standard treatments (BCG, restaging TURB) and 79 (50.6%) palliative management. Among MIBC, 24 (32%) received standard management (cystectomy, radiotherapy, chemotherapy) and 51 (68%) palliative. Applying standard management in HG NMIBC was an independent prognostic factor of OS (44 months vs. 24, HR 1.95; P = 0.013) and decreased the emergency visit rate (33% vs. 43%). In MIBC, the type of management was not a related to OS (P = 0.439) and did not decrease the emergency visit rate (33% vs. 33%). ASA and Charlson-score were not predictors of OS in HG NMIBC (P = 0.368, P = 0.386) and MIBC (P = 0.511, P = 0.665). CONCLUSIONS: Chronological age should not be a contraindication for applying standard therapies in NMIBC. In MIBC the survival is low regardless of the type of management. The lack of correlation between OS and ASA or Charlson-score raises the necessity of a geriatric assessment for selecting the best treatment strategy.