Definitions, End Points, and Clinical Trial Designs for Bladder Cancer: Recommendations From the Society for Immunotherapy of Cancer and the International Bladder Cancer Group.

PURPOSE: There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel. METHODS: Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC. The expert panel also solicited input on the recommendations through presentations and public discussion during an open session at the 2021 Bladder Cancer Advocacy Network (BCAN) Think Tank (held virtually). RESULTS: The consensus panel developed a set of stage-specific bladder cancer clinical trial design recommendations, which are summarized in the table that accompanies this text. CONCLUSION: These recommendations developed by the SITC-IBCG Bladder Cancer Clinical Trial Design consensus panel will encourage uniformity among studies and facilitate drug development in this disease.

Incidental diagnosis of bladder cancer in a national observational study in spain.

INTRODUCTION: Bladder cancer (BC) is a common malignancy in Spain. The aims of this study were: to identify the proportion of patients diagnosed with BC incidentally or after symptomatic presentation in a contemporary period in Spain; to compare demographic, clinical, and pathologic characteristics between these groups. METHODS: This was a retrospective analysis of a multi-centre observational study of 26 hospitals in the Spanish National Health System of all BCs newly diagnosed in 2011. The study represented 21.5% of the Spanish population and hospitals were selected in proportion to Spain's regions to ensure a representative sample. Patients were categorized by whether the cancer was diagnosed incidentally or after symptomatic presentation and baseline demographic, pathologic, and clinical characteristics were analyzed. RESULTS: 2472 were newly diagnosed with BC at the 26 participating Spanish hospitals with 308 (12.5%) of cases diagnosed incidentally and 2164 (87.5%) diagnosed after symptomatic presentation. No differences were observed between patients diagnosed incidentally vs. symptomatically in terms of demographics or measured co-morbidities. Compared to symptomatically diagnosed bladder tumours, those diagnosed incidentally were more likely to have a papillary appearance, to be significantly smaller, and less likely to have positive/suspicious cytology. Additionally, incidentally diagnosed bladder tumours were less likely to be muscle-invasive (11.7% vs. 25.0%, p < 0.01) nor aggressive at pathology, with 33.6% Grade 3 compared to 50.1%, (p < 0.01). CONCLUSIONS: We identified a significant percentage (12.5%) of new bladder cancer diagnosis made incidentally in a representative sample of the Spanish population. These tumours exhibited less aggressive pathologic characteristics than their symptomatic counterparts.

Can cystinuria decrease the effectiveness of RIRS with high-power ho:yag laser in children? Outcomes from a tertiary endourology referral center.

Cystinuria, which is the cause of cystine urolithiasis, accounts for 2-6% of all urinary stones in children, has a low prevalence with a high recurrence rate, making this metabolic disorder a therapeutic challenge in pediatric population. The aim of this work is evaluate the efficacy and safety of retrograde intra-renal surgery (RIRS) in pediatric patients with cystinuria and kidney stones smaller than 2 cm. Prospective study of 64 stones treated in 22 retrograde intra-renal surgeries (RIRS) in cystinuric pediatric patients with renal or proximal ureteral stones less than 2 cm. Average age of 9.5 years. The following data were analyzed: demographics, stone characteristics and surgical data with intra- and postoperative complications. Location of the stones was 68.7% in the calyces, 20.3% in the renal pelvis, and 9.3% in the ureteropelvic junction; 41% of cases had multiple locations. The average cystinuria level before the procedure was 825 mg/dL. The anatomy of 73% of the interventions increased the difficulty of flexible ureteroscopy and decreased stone free rates, because distorted renal anatomy was present: sclerosis of the pelvis or infundibulum, abnormal calyceal dilations, or excluded calyces. Intraoperative complications occurred in 18.2% of the procedures. Reno-vesical ultrasound was performed in all patients in the first postoperative month, with an SFR of 59%. Cystinuric patients are a challenge for pediatric urologists, decreasing the effectiveness of RIRS. However, it could be better treatment than SWL and with fewer complications than PCNL in the pediatric population with this disease.

Non-muscle-invasive bladder cancer: An overview of potential new treatment options.

AIM: This review article summarizes the current clinical practice guidelines around disease definitions and risk stratifications, and the treatment of non-muscle-invasive bladder cancer (NMIBC). Recently completed and ongoing clinical trials of novel and investigational therapies in Bacillus Calmette-Guérin (BCG)-naïve, BCG-recurrent, and BCG-unresponsive patient populations are also described, e.g., those involving immune checkpoint inhibitors, targeted therapies, other chemotherapy regimens, vaccines, and viral- or bacterial-based treatments. Finally, a brief overview of enhanced cystoscopy and drug delivery systems for the diagnosis and treatment of NMIBC is provided. BACKGROUND: A global shortage of access to BCG is affecting the management of BCG-naïve and BCG-recurrent/unresponsive NMIBC; hence, there is an urgent need to assist patients and urologists to enhance the treatment of this disease. METHODS: Searches of ClinicalTrials.gov, PubMed, and Google Scholar were conducted. Published guidance and conference proceedings from major congresses were reviewed. CONCLUSION: Treatment strategies for NMIBC are generally consistent across guidelines. Several novel therapies have demonstrated promising antitumor activity in clinical trials, including in high-risk or BCG-unresponsive disease. The detection, diagnosis, surveillance, and treatment of NMIBC have also been improved through enhanced disease detection.

Radiation-induced haemorrhagic cystitis after prostate cancer radiotherapy: factors associated to hospitalization and treatment strategies.

BACKGROUND: Late onset of radiation-induced haemorrhagic cystitis (RHC) after radiation therapy (RT) for prostate cancer (PCa) may present or evolve severely, requiring hospitalization with invasive interventions. In the present study, we have analysed the prevalence and risk factors associated with the onset of RHC. METHODS: From January 2002 to May 2017, 1421 patients undertook RT for PCa as a primary, adjuvant, or salvage treatment option. RHC presented in 5.6% (n = 80) of the patients; the diagnosis was based on clinical and endoscopic characteristics. Variables in observation included patients, tumours, and RT-dosimetry characteristics. Patients with a previous history of bladder cancer were excluded. Univariate (Student t/Chi square) and uni-/multivariate Cox regression analysis were performed; the events and time-points were hospitalization and time-to-event, respectively. RESULTS: There were 80 patients with a mean age at RT of 70.1 years (SD 6.4), mean time lag to RHC of 43.9 months (SD 37.5). Median Emergency attendance was two and three times for patients without/with hospitalization, respectively. There were in total 64 admissions with invasive treatment required in 26/36 (72.2%) of the patients hospitalised, including transurethral fulguration in 22 and radical cystectomy in 5. Patients at higher risk of hospitalization were those undertaking antiplatelet/anticoagulant treatment (HR:3.30; CI 95%:1.53-3.30; p = 0.002) and those treated with salvage RT with higher bladder volume receiving >70 Gy (bladder V70) (HR:1.03; CI 95%:1.01-1.05; p = 0.027). At receiving operating characteristic analysis, the cutoff for bladder V70 was 29%. CONCLUSION: Nearly half of patients presenting RHC may require invasive treatment including cystectomy. Risk factors associated with hospitalization are patients undertaking antiplatelet/coagulant treatment and bladder V70 > 29% in salvage RT patients.

Pelvic Organ Prolapse Repair with Mesh: Description of Surgical Technique Using the Surelift® Anterior Repair System.

INTRODUCTION: Although the use of transvaginal mesh (TVM) in the repair of pelvic organ prolapse (POP) has been restricted, there are still some cases in which TVM may be the most appropriate approach. The TVM Surelift® anterior repair surgical technique has not been described previously. OBJECTIVE: The aim of this study was to describe the surgical technique and to report our preliminary results regarding efficacy and complications. METHODS: A step-by-step description of surgical technique is presented. A descriptive retrospective analysis was performed to evaluate our preliminary results in 17 women who underwent POP repair using the Surelift® anterior repair system in our department between 2014 and 2017. TVM was offered to patients with symptomatic apical (primary or recurrent) or recurrent anterior POP stage ≥2. POP recurrence was classified as asymptomatic anatomic or symptomatic. Patients rated satisfaction with surgery on a scale from 0 to 10. Complications during follow-up were classified according to the International Urogynecological Association/International Continence Society recommendations. RESULTS: Median (IQR) follow-up was 19.9 months (24.8). Two (11.8%) anatomic recurrences were identified, both symptomatic, but neither required further surgery. No cases of pelvic pain, dyspareunia, voiding, or defecatory dysfunction were detected. Two (11.8%) patients presented a <1-cm vaginal mesh exposure (2AaT3S2) requiring partial mesh removal through a vaginal approach. At the end of follow-up, median satisfaction (IQR) with the surgery was 9 (3.1). CONCLUSION: The Surelift® anterior repair system is effective in correcting apical or recurrent anterior POP, with a high patient satisfaction rate. Complications after this surgery are infrequent and are mostly related to vaginal mesh exposure.

Non-technical skills for urological surgeons (NoTSUS): development and evaluation of curriculum and assessment scale.

OBJECTIVE: In the last decade non-technical skills (NTS) have emerged as a vital area for improvement within surgery. This study aims to develop and evaluate a Non-technical Skills for Urological Surgeons (NoTSUS) training curriculum and assessment scale. METHODS: This international, longitudinal and observational study began with a 3-round Delphi methodology to refine curriculum contents and rating scale. Sessions with up to four participants were delivered where each candidate undertook an independent scenario within the validated full immersion simulation environment. Candidates were assessed using both the NoTSS (Non-technical Skills for Surgeons) and NoTSUS rating scales by NTS-trained and non-trained experts. A post-training evaluation survey was distributed. RESULTS: 62 participants comprising trainees (n = 43) and specialists (n = 19) undertook the NoTSUS course. The NoTSS and NoTSUS scales correlated well, with a mean difference of 3.3 in the overall total (p = 0.10, r = 0.53). However, there was significant differences in scores between the NoTSS-trained and non-trained raters (n = 28, p = 0.03). A one-way ANOVA test revealed significant improvement throughout the four simulation scenarios in each session (p = 0.02). The NoTSUS curriculum received positive feedback from participants and demonstrated educational value and acceptability. CONCLUSIONS: The NoTSUS curriculum has demonstrated high educational value for NTS training aimed at urologists, with marked improvement throughout sessions. Correlation of NoTSUS and NoTSS scales proves its suitability for evaluating NTS in future training. Demonstration of inter-rater reliability indicates that the scale is reliable for use in assessment by expert faculty members. Furthermore, qualitative feedback from participants suggests gain of transferrable skills over the course.

Consensus Definition and Prediction of Complexity in Transurethral Resection or Bladder Endoscopic Dissection of Bladder Tumours.

Ten senior urologists were interrogated to develop a predictive model based on factors from which they could anticipate complex transurethral resection of bladder tumours (TURBT). Complexity was defined by consensus. Panel members then used a five-point Likert scale to grade those factors that, in their opinion, drove complexity. Consensual factors were highlighted through two Delphi rounds. Respective contributions to complexity were quantitated by the median values of their scores. Multivariate analysis with complexity as a dependent variable tested their independence in clinical scenarios obtained by random allocation of the factors. The consensus definition of complexity was "any TURBT/En-bloc dissection that results in incomplete resection and/or prolonged surgery (>1 h) and/or significant (Clavien-Dindo ≥ 3) perioperative complications". Logistic regression highlighted five domains as independent predictors: patient's history, tumour number, location, and size and access to the bladder. Receiver operating characteristic (ROC) analysis confirmed good discrimination (AUC = 0.92). The sum of the scores of the five domains adjusted to their regression coefficients or Bladder Complexity Score yielded comparable performance (AUC = 0.91, C-statistics, p = 0.94) and good calibration. As a whole, preoperative factors identified by expert judgement were organized to quantitate the risk of a complex TURBT, a crucial requisite to personalise patient information, adapt human and technical resources to individual situations and address TURBT variability in clinical trials.

Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group.

BACKGROUND: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. OBJECTIVE: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥ 75 years of age. METHODS: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (less than 75 vs. ≥75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. RESULTS: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p less than 0.01) and higher ASA score (ASA > 2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p less than 0.01), EBL ≥ 500 cc (OR 3.34, p less than 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. CONCLUSIONS: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities.

Characteristics and Surgical Outcomes in Very Elderly Patients (≥75 years) with Renal Cell Carcinoma: Data from the Latin American Renal Cancer Group

Background: The incidence of renal cell carcinoma (RCC) is increasing globally due to an aging population and widespread use of imaging studies. Objective: The aim of this study was to describe the characteristics and perioperative outcomes of RCC surgery in very elderly patients (VEP), ≥75 years of age. Methods: This is a retrospective comparative study of 3656 patients who underwent the treatment for RCC from 1990 to 2015 in 28 centers from eight Latin American countries. We compared baseline characteristics as well as clinical and perioperative outcomes according to age groups (<75 vs.≥ 75 years). Surgical complications were classified with the Clavien-Dindo score. We performed logistic regression analysis to identify factors associated with perioperative complications. Results: There were 410 VEP patients (11.2%). On bivariate analysis, VEP had a lower body mass index (p < 0.01) and higher ASA score (ASA >2 in 26.3% vs. 12.4%, p < 0.01). There was no difference in performance status and clinical stage between the study groups. There were no differences in surgical margins, estimated blood loss (EBL), complication, and mortality rates (1.3% vs. 0.4%, p = 0.17). On multivariate regression analysis, age ≥75 years (odds ratio [OR] 2.33, p < 0.01), EBL ≥ 500 cc (OR 3.34, p < 0.01), and > pT2 stage (OR 1.63, p = 0.04) were independently associated with perioperative complications. Conclusions: Surgical resection of RCC was safe and successful in VEP. Age ≥75 years was independently associated with 30-day perioperative complications. However, the vast majority were low-grade complications. Age alone should not guide decision-making in these patients, and treatment must be tailored according to performance status and severity of comorbidities. (REV INVEST CLIN. 2020;72(5):308-15)

A comparative propensity score-matched analysis of perioperative outcomes of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVE: To compare the perioperative outcomes of intracorporeal (ICUD) vs extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC). PATIENTS AND METHODS: We retrospectively reviewed the prospectively maintained International Robotic Cystectomy Consortium (IRCC) database. A total of 972 patients from 28 institutions who underwent RARC were included. Propensity score matching was used to match patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists Score (ASA) score, Charlson Comorbidity Index (CCI) score, prior radiation and abdominal surgery, receipt of neoadjuvant chemotherapy, and clinical staging. Matched cohorts were compared. Multivariate stepwise logistic and linear regression models were fit to evaluate variables associated with receiving ICUD, operating time, 90-day high-grade complications (Clavien-Dindo Classification Grade ≥III), and 90-day readmissions after RARC. RESULTS: Utilisation of ICUD increased from 0% in 2005 to 95% in 2018. The ICUD patients had more overall complications (66% vs 58%, P = 0.01) and readmissions (27% vs 17%, P = 0.01), but not high-grade complications (21% vs 24%, P = 0.22). A more recent RC era and ileal conduit diversion were associated with receiving an ICUD. Higher BMI, ASA score ≥3, and receiving a neobladder were associated with longer operating times. Shorter operating time was associated with male gender, older age, ICUD, and centres with a larger annual average RC volume. Longer intensive care unit stay was associated with 90-day high-grade complications. Higher CCI score, prior radiation therapy, neoadjuvant chemotherapy, and ICUD were associated with a higher risk of 90-day readmissions. CONCLUSIONS: Utilisation of ICUD has increased over the past decade. ICUD was associated with more overall complications and readmissions compared to ECUD, but not high-grade complications.

Treatment Response and Complications after Intradetrusor OnabotulinumtoxinA Injection in Male Patients with Idiopathic Overactive Bladder Syndrome.

PURPOSE: We sought to assess the treatment response, complications and treatment continuation after onabotulinumtoxinA injection in male patients. MATERIALS AND METHODS: We performed a retrospective study of men with refractory idiopathic overactive bladder treated with intradetrusor injection of 100 IU onabotulinumtoxinA since 2007 in our department. Patients with previous radical prostatectomy were excluded from analysis. The treatment response was assessed using a treatment benefit scale of 1-greatly improved, 2-improved, 3-not changed and 4-worse after treatment. A treatment benefit scale score of 1 or 2 was considered a treatment response. Complications were classified according to the CD (Clavien-Dindo) classification. Treatment was considered to have continued if at the last visit patients had received an onabotulinumtoxinA injection within the preceding 12 months. We performed univariate and multivariate analyses to assess factors predictive of the treatment response, complications and continuation on treatment. RESULTS: Of the 146 men with a mean ± SD age of 70.1 ± 13.3 years who were included in study 91 (62.3%) reported a response to treatment. A total of 24 complications (16.4%) were detected, including 19 cases (13%) of urinary retention (CD 2), 2 (1.3%) of hematuria (CD 1) and 3 (2%) of urinary infection (CD 2). Followup was more than 12 months in 128 patients, of whom 88 (68.8%) had discontinued treatment by the end of followup. A higher bladder outlet obstruction index was the only factor predicting a lower treatment response rate and a higher complication rate. CONCLUSIONS: Most male patients with idiopathic overactive bladder showed a treatment response after intradetrusor onabotulinumtoxinA injection. However, the majority discontinued treatment. A higher bladder outlet obstruction index was related to a lower treatment response and a higher complication rate.

Simultaneous and synchronous bilateral endoscopic treatment of urolithiasis: a multicentric study.

INTRODUCTION: The general prevalence of bilateral urolithiasis has risen to 15% and bilateral non-simultaneous treatment has been reported to have good outcomes. The objective of this study was to evaluate the effectiveness and safety of simultaneous bilateral endoscopic surgery (SBES). MATERIAL AND METHODS: An international multicenter analysis was performed between May 2015 and December 2017. All patients with bilateral stone disease that underwent SBES were included. Patients were treated under general anesthesia in either the supine or lithotomy position. Demographic, clinical, intraoperative and postoperative data were analyzed. RESULTS: A total of 47 patients were included. Mean age was 53.8 years and 70% of the patients were males. The mean American Society of Anesthesiology (ASA) score was 2. The mean diameter of right- and left-sided stones was 29.43 mm (2-83 mm) and 31.15 (4-102 mm), respectively. Staghorn stones were treated in 18 cases (8 right-sided and 10 left-sided), four of them were defined as complete staghorn. The procedures performed were 42 cases of bilateral URS and PCNL and ureteroscopy. Additionally, 5 bilateral flexible ureteroscopy (fURS) cases were described. Intraoperative complications occurred in five patients: four of them were classified as Clavien-Dindo (CD) I and one as CD II. Postoperatively, there were two cases with CD I, 6 with CD II and one CD IIIa.The stone-free status was 70%. Residual stones (30%) were detected only on the side treated for high-volume (complete) staghorn calculi. CONCLUSIONS: SBES is a feasible, effective and safe procedure. It may potentially avoid repeated anesthetic sessions as needed for staged procedures and reduce the length of patients' hospital stay.

Robot-assisted Radical Prostatectomy Due to a Primary Carcinoid Prostatic Tumor in a Three-Year-Old Child: A Case Report.

We present an extremely rare case of a 3-year-old child with a primary carcinoid tumor of the prostate. A 3-year-old boy presented with failure to thrive, constipation, recurrent respiratory tract infections, and pain in the genital area. His karyotype was normal and cystic fibrosis and coeliac disease were excluded prior to further investigation. An abdominopelvic computed tomography scan revealed a prostatic mass. Transrectal ultrasound-guided prostate biopsy was therefore performed and pathological examination revealed a carcinoid tumor. A robotic radical prostatectomy was performed. As this is an innovative surgical approach, we describe the surgical technique used.

Long-term follow-up after cystectomy for bladder pain syndrome: pain status, sexual function and quality of life.

PURPOSE: To assess the long-term complications, pain status, sexual function and quality of life after cystectomy for bladder pain syndrome (BPS). METHODS: We retrospectively reviewed functional variables for 35 patients (34 women/1 man, 67 ± 9 years old) who underwent cystectomy due to BPS since 1993 in our department. Cystectomy was offered to patients with BPS refractory to conservative treatments. Six cystectomies with ileal conduit (17.1%) and 29 supratrigonal cystectomies with enterocystoplasty (82.9%) were performed. Prospectively, patients completed questionnaires on pain [BPIC-SS, visual analogue scale (VAS) for pain], health-related quality of life (EQ-5D) and sexual function (FSFI; 2-36), rated satisfaction with surgery (0-10) and reported whether they would undergo the same surgery again. RESULTS: Mean follow-up was 107 ± 83 months. In two (5.7%) patients, pain persisted and in one patient (2.8%) pain recurred after 20 months. Significant improvements in daytime and nighttime frequency and bladder capacity were observed postoperatively. 21 patients completed questionnaires. Mean BPIC-SS was 7.5 ± 8.4, mean VAS score 2.5 ± 2.8. 14 (66.7%) patients reported no problems related to pain on the EQ-5D, similar to our regional reference population. 13 (61.9%) patients had sexual intercourse after surgery, ten of them without pain. Mean FSFI score was 9.5 ± 9. Satisfaction with surgery was 8.8 ± 1.7 and 20 (95.2%) patients would undergo the same surgery again. CONCLUSION: Pain persistence or recurrence after cystectomy for BPS is infrequent. Quality of life related to pain is similar to that in the general population and patients can resume sexual activity without pain.

Pelvic Organ Prolapse Repair with Mesh: Mid-Term Efficacy and Complications.

INTRODUCTION: Our aim was to assess the efficacy and complications of pelvic organ prolapse (POP) correction with transvaginal mesh (TVM). MATERIALS AND METHODS: We retrospectively assessed patients who had undergone a repair of an apical (primary or recurrent) or recurrent POP using TVM in our department since 2007. Meshes used were Prolift®, Elevate®, and Surelift®. Satisfaction with surgery was assessed on a 0-10 scale. RESULTS: A total of 83 patients were included (33 Prolift®, 36 Elevate®, 14 Surelift®), with a mean age of 67.8 ± 9.7 years. Eighteen (21.6%) patients underwent a recurrent POP correction. Follow-up was 49 ± 34 months. Twelve (14.4%) symptomatic recurrences were identified, 3 of which required further surgery. Satisfaction was 8.7. Four (4.8%) vaginal exposures were detected, 2 of which required partial mesh removal. Three (3.6%) cases of dyspareunia and 1 (1.2%) case of mild pelvic pain were reported, which did not require further treatment. CONCLUSION: The use of TVM for apical or recurrent POP repair is effective and is associated with a high satisfaction rate while complications are infrequent.

[BCG and bladder cancer: Past, present and future.] / BCG y cáncer de vejiga: pasado, presente y futuro.

BCG has been used in the treatment of NMIBC for more than 40 years. Nevertheless, its exact working mechanisms have not been completely discovered. Clinical and basic research done over all these years has generated much information but it could be summarized in a few simple statements. It has been demonstrated the best route of administration is intravesical, BCG is superior than intracavitary chemotherapy to prevent recurrence but its adverse events are worse. Recently, it has been demonstrated that BCG could delay or prevent progression to infiltrative cancer. Nevertheless, to achieve this, maintenance therapy is necessary. Therefore, the recommendation is to treat middle and high risk cases with BCG. No significant differences in efficacy have been found between the various strains but differences in recurrence have been found between standard and reduced doses.Furthermore, the presence or absence of side effects does not seem to be a prognostic factor for the efficacy of BCG and, maintenance therapy is not associated with a significant increase in toxicity. In the future, the optimal schedule and doses must be defined, and it probably will be different for each individual. BCG shortage has led to try alternative therapies through chemo hyperthermia or electrical gradient application the efficacy of which should be evaluated. New strains and immunological treatments are also under research.

Inmunoterapia con BCG BCG y cáncer de vejiga: pasado, presente y futuro / BCG and bladder cancer: Past, present and future

Hace más de 40 años que se utiliza la BCG en el tratamiento del CVNMI. Sin embargo, los mecanismos de trabajo exactos de su funcionamiento aún no han sido totalmente descubiertos. La investigación clínica y básica realizada durante todos estos años ha generado mucha información pero que podría resumirse en unas pocas afirmaciones sencillas. Se ha demostrado que la mejor vía de administración de BCG es la vía intravesical, que la BCG es superior a la quimioterapia intracavitaria para prevenir la recurrencia pero que sus efectos adversos son peores. Recientemente se ha demostrado que BCG podría prevenir o retrasar la progresión a cáncer infiltrante. Sin embargo, para lograr esto, la terapia de mantenimiento es necesaria. Por ello, se recomienda que los tumores de riesgo intermedio y alto se traten con BCG. No se han encontrado diferencias significativas en la eficacia entre las diferentes cepas, pero si diferencia de recurrencia en la utilización de una dosis estándar frente a una reducida. Además, la presencia o ausencia de efectos secundarios no parece ser un factor pronóstico para la eficacia de BCG y la terapia de mantenimiento no se asocia con un aumento significativo de la toxicidad. En el futuro, se debe definir el esquema y la dosis óptimos, y esto probablemente sea diferente para cada individuo. La falta de suministros de BCG ha hecho que se prueben terapias alternativas mediante quimiohipertermia o aplicación de un gradiente eléctrico cuya efectividad debe ser evaluada. Nuevas cepas y tratamientos inmunológicos están también siendo investigados

BCG has been used in the treatment of NMIBC for more than 40 years. Nevertheless, its exact working mechanisms have not been completely discovered. Clinical and basic research done over all these years has generated much information but it could be summarized in a few simple statements. It has been demonstrated the best route of administration is intravesical, BCG is superior than intracavitary chemotherapy to prevent recurrence but its adverse events are worse. Recently, it has been demonstrated that BCG could delay or prevent progression to infiltrative cancer. Nevertheless, to achieve this, maintenance therapy is necessary. Therefore, the recommendation is to treat middle and high risk cases with BCG. No significant differences in efficacy have been found between the various strains but differences in recurrence have been found between standard and reduced doses. Furthermore, the presence or absence of side effects does not seem to be a prognostic factor for the efficacy of BCG and, maintenance therapy is not associated with a significant increase in toxicity. In the future, the optimal schedule and doses must be defined, and it probably will be different for each individual. BCG shortage has led to try alternative therapies through chemo hyperthermia or electrical gradient application the efficacy of which should be evaluated. New strains and immunological treatments are also under research

Análisis de tolerancia y seguridad de la quimiohipertermia con Mitomicina C en el tratamiento del cáncer de vejiga no músculo invasivo / Analysis of tolerance and security of chemo hyperthermia with Mitomycin C for the treatment of non-muscle invasive bladder cancer

OBJETIVO: El tratamiento del cáncer de vejiga no músculo invasivo (CVNMI) continúa siendo un reto. La hipertermia (HT) combinada con la quimioterapia intravesical se usa para mejorar los efectos de la quimioterapia. MÉTODOS: Se realizó una revisión de las publicaciones para sintetizar los efectos adversos (EA) reportados por el uso de la quimiohipertermia (QHT) con Mitomicina- C (MMC). Se exponen los datos más relevantes para cada uno de los dispositivos empleados actualmente en la QHT. RESULTADOS: SYNERGO(R): La tasa de abandono varió entre 3-40%, y la tasa de EA es de hasta el 88%. Los EA con mayor frecuencia fueron dolor (2-40%), reacción térmica de la pared posterior (13-100%), espasmos vesicales (2-32%), disuria (3-60%) y hematuria (2-62%).COMBAT BRS®: La tasa de abandono de tratamiento es del 3-11%. Los EA reportados fueron CTCAE Grado 1-2: Dolor 13-27%, espasmos vesicales 6-27% y hematuria 3-20% son los más relevantes. En general, no se informan de toxicidad CTCAE grado 3-4. UNITHERMIA(R): La tasa de abandono de tratamiento es del 7-12%. Los EA descritos son: Dolor 6-23%, espasmos vesicales 6-23%, hematuria 9-11%, frecuencia 15-25% y alergia 6-11. La mayoría de las toxicidades son CTCAE grado 1-2 (17-53%), siendo grado 3-4 en 9-15% y Grado 5 en 0-2%. La QHT añade poco a los EA del tratamiento con MMC. No agrega efectos severos, no incrementa de forma significativa los abandonos al tratamiento, y no aumenta la incidencia de reacciones alérgicas. El estudio comparativo entre BCG y QHT-MMC encuentra menor probabilidad de presentar frecuencia miccional, nicturia, incontinencia, hematuria, fiebre, fatiga y artralgia, en los pacientes del grupo de QHT. CONCLUSIONES: La QHT ha demostrado ser una alternativa segura para el tratamiento de los CVNMI de riesgo intermedio y alto, con EA principalmente grado 1-2. Los EA reportados tienen poca variación con respecto a la dosis de MMC empleada, presentando diferentes "perfiles" relacionados con el dispositivo usado para su administración. Los tratamientos con QHT-MMC son bien tolerados, sin añadir significativamente más EA que las instilaciones de MMC sola y presentando mejor perfil de toxicidad que los reflejados en la literatura con respecto al tratamiento con BCG

OBJECTIVES: The treatment of non muscle invasive bladder cancer (NMIBC) continues to be a challenge. Hyperthermia(HT) combined with intravesical chemotherapy is used to enhance the effects of chemotherapy. METHODS: A review of the publications was carried out to synthesize the adverse effects (AE) reported by the use of chemohyperthermia (QHT) with Mitomycin-C (MMC). The most relevant data are exposed for each of the devices currently used in the QHT. RESULTS: SYNERGO(R): The dropout rate varied between 3-40%, and the AE rate is up to 88%. The most common AEs were pain (2-40%), thermal reaction of the posterior wall (13-100%), bladder spasms (2-32%), dysuria (3-60%) and hematuria (2-62%). COMBAT BRS(R): The dropout rate is 3-11%. The AEs reported were CTCAE Grade 1-2: Pain 13-27%, bladder spasms 6-27% and hematuria 3-20% are the most relevant. In general, CTCAE grade 3-4 toxicity is not reported. UNITHERMIA(R): The dropout rate is 7-12%. The AEs described are: Pain 6-23%, bladder spasms 6-23%, hematuria 9-11%, frequency 15-25% and allergy 6-11%. The majority of toxicities are CTCAE grade 1-2 (17-53%), with grade 3-4 in 9-15% and Grade 5 in 0-2%. QHT adds little to the AEs of the treatment with MMC. It neither adds severe effects, nor increases dropouts significantly, and does not increase the incidence of allergic reactions. The comparative study between BCG and QHT-MMC, is less likely to present urinary frequency, nocturia, incontinence, hematuria, fever, fatigue and arthralgia in patients in the QHT group. CONCLUSIONS: QHT has proven to be a safe alternative for the treatment of intermediate and high risk NMIBC, with AE mainly grade 1-2. The AEs reported have little variation with respect to the dose of MMC used, presenting different "profiles" related to the device used for its administration. The treatments with QHTMMC are well tolerated, without adding significantly more AE than the instillations of MMC alone and presenting a better toxicity profile than those reflected in the literature with respect to the treatment with BCG