M.J. Ribal

Treatment of Muscle-Invasive and Metastatic Bladder Cancer: Update of the EAU Guidelines.

CONTEXT New data regarding treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE To review the new EAU guidelines for MiM-BC with a specific focus on treatment. EVIDENCE ACQUISITION New literature published since the last update of the EAU guidelines in 2008 was obtained from Medline, the Cochrane Database of Systematic Reviews, and reference lists in publications and review articles and comprehensively screened by a group of urologists, oncologists, and a radiologist appointed by the EAU Guidelines Office. Previous recommendations based on the older literature on this subject were also taken into account. Levels of evidence (LEs) and grades of recommendations (GRs) were added based on a system modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS Current data demonstrate that neoadjuvant chemotherapy in conjunction with radical cystectomy (RC) is recommended in certain constellations of MiM-BC. RC remains the basic treatment of choice in localised invasive disease for both sexes. An attempt has been made to define the extent of surgery under standard conditions in both sexes. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. In contrast to neoadjuvant chemotherapy, current advice recommends the use of adjuvant chemotherapy only within clinical trials. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for medical or personal reasons. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin remains cisplatin-containing combination chemotherapy. With the advent of vinflunine, second-line chemotherapy has become available. CONCLUSIONS In the treatment of localised invasive bladder cancer (BCa), the standard treatment remains radical surgical removal of the bladder within standard limits, including as-yet-unspecified regional lymph nodes. However, the addition of neoadjuvant chemotherapy must be considered for certain specific patient groups. A new drug for second-line chemotherapy (vinflunine) in metastatic disease has been approved and is recommended.

EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2013 Guidelines

CONTEXT The European Association of Urology (EAU) guidelines panel on Muscle-invasive and Metastatic bladder cancer (BCa) updates its guidelines yearly. This updated summary provides a synthesis of the 2013 guidelines document, with emphasis on the latest developments. OBJECTIVE To provide graded recommendations on the diagnosis and treatment of patients with muscle-invasive BCa (MIBC), linked to a level of evidence. EVIDENCE ACQUISITION For each section of the guidelines, comprehensive literature searches covering the past 10 yr in several databases were conducted, scanned, reviewed, and discussed both within the panel and with external experts. The final results are reflected in the recommendations provided. EVIDENCE SYNTHESIS Smoking and work-related carcinogens remain the most important risk factors for BCa. Computed tomography (CT) and magnetic resonance imaging can be used for staging, although CT is preferred for pulmonary evaluation. Open radical cystectomy with an extended lymph node dissection (LND) remains the treatment of choice for treatment failures in non-MIBC and T2-T4aN0M0 BCa. For well-informed, well-selected, and compliant patients, however, multimodality treatment could be offered as an alternative, especially if cystectomy is not an option. Comorbidity, not age, should be used when deciding on radical cystectomy. Patients should be encouraged to actively participate in the decision-making process, and a continent urinary diversion should be offered to all patients unless there are specific contraindications. For fit patients, cisplatinum-based neoadjuvant chemotherapy should always be discussed, since it improves overall survival. For patients with metastatic disease, cisplatin-containing combination chemotherapy is recommended. For unfit patients, carboplatin combination chemotherapy or single agents can be used. CONCLUSIONS This 2013 EAU Muscle-invasive and Metastatic BCa guidelines updated summary aims to increase the quality of care and outcome for patients with muscle-invasive or metastatic BCa. PATIENT SUMMARY In this paper we update the EAU guidelines on Muscle-invasive and Metastatic bladder cancer. We recommend that chemotherapy be administered before radical treatment and that bladder removal be the standard of care for disease confined to the bladder.

The updated EAU guidelines on muscle-invasive and metastatic bladder cancer.

CONTEXT New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. OBJECTIVE To review the new EAU guidelines for MiM-BC. EVIDENCE ACQUISITION A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. EVIDENCE SYNTHESIS The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. CONCLUSIONS These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse.

Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer

CONTEXT Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. OBJECTIVE To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. EVIDENCE ACQUISITION An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. EVIDENCE SYNTHESIS Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. CONCLUSIONS The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. PATIENT SUMMARY Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.

Feasibility of Transvaginal NOTES-Assisted Laparoscopic Nephrectomy

BACKGROUND Recently, the feasibility of a transvaginal hybrid natural orifice transluminal endoscopic surgery (NOTES) nephrectomy was demonstrated in a 23-yr-old woman with a nonfunctional atrophic kidney. OBJECTIVE To evaluate the feasibility and reproducibility of transvaginal NOTES-assisted laparoscopic nephrectomy in female patients with and without renal cancer. DESIGN, SETTING, AND PARTICIPANTS Between March 2008 and June 2009, 14 female patients were submitted to transvaginal NOTES-assisted laparoscopic nephrectomy for T1-T3a N0M0 renal cancer (n=10), lithiasis (n=2), or renal atrophy (n=2) at the Hospital Clinic of Barcelona, Spain. SURGICAL PROCEDURE Under general anaesthesia, female patients underwent laparoscopic nephrectomy by transvaginal NOTES using a deflectable camera by vaginal access and two additional 5- and 10-mm trocars in the abdomen. The renal artery and vein were dissected and taken separately between clips. The dissected kidney was removed via the vagina after enlarging the vaginal trocar incision. MEASUREMENTS All data referring to patient demographics, surgery, pathology, and perioperative outcomes were recorded. RESULTS AND LIMITATIONS The procedure was completed in all patients. The mean age of the women was 59.1 yr. The mean operative time was 132.9 min and the mean estimated blood loss was 111.2 ml. None of the patients required a blood transfusion and the use of analgesics was low. The mean hospital stay was 4 d. In one case, a major complication (a colon injury) occurred. The patient underwent surgery and a temporary colostomy was performed. The patient has already undergone reconstruction. CONCLUSIONS Transvaginal NOTES-assisted laparoscopic nephrectomy is feasible and reproducible and may be an alternative technique for treatment of women with renal cancer. Proper selection of patients is warranted for success of this new approach. However, longer follow-up in an increasing number of patients is needed to establish its role in the treatment of renal cancer.

Where do we really stand with LESS and NOTES

Matthew T. Gettman *, Wesley M. White, Monish Aron, Riccardo Autorino, Tim Averch, Geoffrey Box, Jeffrey A. Cadeddu, David Canes, Edward Cherullo, Mihir M. Desai, Igor Frank, Indebir S. Gill, Mantu Gupta, Georges-Pascal Haber, Mitchell R. Humphreys, Brian H. Irwin, Jihad H. Kaouk, Louis R. Kavoussi, Jaime Landman, Evangelos N. Liatsikos, Estevao Lima, Lee E. Ponsky, Abhay Rane, Maria Ribal, Robert Rabenhalt, Pradeep Rao, Lee Richstone, Mark D. Sawyer, Rene Sotelo, Jens-Uwe Stolzenburg, Chad R. Tracy, Robert J. Stein; Endourological Society NOTES and LESS Working Group; European Society of Urotechnology NOTES and LESS Working Group E U RO P E AN URO LOGY 5 9 ( 2 0 1 1 ) 2 3 1 – 2 3 4

The Impact of the Extent of Lymphadenectomy on Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Systematic Review

CONTEXT Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS Twenty-three studies reporting on 19,793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

Follow-up After Surgical Treatment of Bladder Cancer: A Critical Analysis of the Literature

CONTEXT Follow-up of patients treated for bladder cancer (BCa) is of great importance for both non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) because of the high incidence of recurrence and progression. The schedule and methods of follow-up should reflect the individual clinical situation. OBJECTIVE To evaluate the existing evidence for intensity and duration of follow-up recommendations in patients after surgical treatment of BCa. EVIDENCE ACQUISITION We searched the Medline, Embase, and Cochrane databases for published data on the follow-up of patients with NMIBC and MIBC after radical cystectomy (RC). EVIDENCE SYNTHESIS Follow-up in patients with NMIBC is necessary because of the high probability of tumour recurrence and the risk of progression. Cystoscopy plus cytology are the standard methods for follow-up. Cystoscopy should be done 3 mo after the transurethral resection in every patient, and the frequency after that depends on the individual recurrence/progression risk. Cytology should be used as an adjunctive method to cystoscopy in intermediate- and high-risk patients. None of the currently available urinary markers or imaging methods can substitute for cystoscopy-based follow-up. High-risk NMIBC patients require regular lifelong upper urinary tract monitoring. Follow-up in MIBC is based on the fact that early detection of recurrence after RC allows for timely treatment with the aim of improving outcomes. Patients with extravesical and lymph node-positive disease should have the most intensive follow-up because of the highest recurrence risk. Routine upper urinary tract imaging is advisable for all patients and should continue in the long term. Follow-up also allows for early detection of urinary diversion-related complications, the rate of which increases with time. CONCLUSIONS Follow-up in BCa is necessary for diagnosing recurrence and progression, as well as for evaluating complications after radical treatment. Since randomised studies investigating the most appropriate follow-up schedule are lacking, most recommendations are based on only the retrospective experience. Nonetheless, reasonable recommendations can be made until further prospective randomised studies testing different follow-up schedules have been performed.

Feasibility of transvaginal natural orifice transluminal endoscopic surgery-assisted living donor nephrectomy: is kidney vaginal delivery the approach of the future?

BACKGROUND Natural orifice transluminal endoscopic surgery (NOTES) uses natural orifices to access the abdominal cavity. We adapted NOTES to perform transvaginal NOTES-assisted laparoscopic nephrectomy in living donors. OBJECTIVE To assess the feasibility and reproducibility of this procedure and compare it with conventional laparoscopic living donor nephrectomy (LLDN). DESIGN, SETTING, AND PARTICIPANTS From July 2009 to October 2010, 20 women underwent transvaginal NOTES-assisted living donor nephrectomy (LDN) in our centre. We compared the prospectively collected clinical data of each donor with those of a contemporaneous matched pair of conventional LLDNs (40 donors). SURGICAL PROCEDURE The procedure was performed using three abdominal trocars and one trocar through the vaginal wall. MEASUREMENTS Variables evaluated for donors were procedure length, blood loss, warm ischaemia time (WIT), complications, hospital stay, and first-month creatinine nadir. In the transvaginal LDN group, sexual function was assessed with the Female Sexual Function Index questionnaire before and after surgery. Variables evaluated for recipients were complications, graft function, and creatinine evolution. RESULTS AND LIMITATIONS The procedure was completed in all cases. Operative variables were similar for both groups except for WIT, which was longer in the transvaginal LDN group (p<0.001) without consequences for graft functioning. One transvaginal LDN case had postoperative bleeding requiring immediate open surgery. All transvaginal LDN donors reported unaltered sexual function after surgery and satisfaction with the results. All recipients had immediate urine output, and all had a functioning graft at last follow-up except for one recipient of the transvaginal LDN group who required transplantectomy. Despite promising results, randomised controlled studies with longer follow-up are warranted to further elucidate the potential of this novel technique. CONCLUSIONS Transvaginal NOTES-assisted LDN appears to be a feasible and reproducible surgical technique. The WIT was longer in the transvaginal group, and there was no effect on graft function after the short follow-up.

EAU Guidelines on Primary Urethral Carcinoma

CONTEXT The European Association of Urology (EAU) Guidelines Group on Muscle-Invasive and Metastatic Bladder Cancer prepared these guidelines to deliver current evidence-based information on the diagnosis and treatment of patients with primary urethral carcinoma (UC). OBJECTIVE To review the current literature on the diagnosis and treatment of patients with primary UC and assess its level of scientific evidence. EVIDENCE ACQUISITION A systematic literature search was performed to identify studies reporting urethral malignancies. Medline was searched using the controlled vocabulary of the Medical Subject Headings database, along with a free-text protocol. EVIDENCE SYNTHESIS Primary UC is considered a rare cancer, accounting for <1% of all malignancies. Risk factors for survival include age, tumour stage and grade, nodal stage, presence of distant metastasis, histologic type, tumour size, tumour location, and modality of treatment. Pelvic magnetic resonance imaging is the preferred method to assess the local extent of urethral tumour; computed tomography of the thorax and abdomen should be used to assess distant metastasis. In localised anterior UC, urethra-sparing surgery is an alternative to primary urethrectomy in both sexes, provided negative surgical margins can be achieved. Patients with locally advanced UC should be discussed by a multidisciplinary team of urologists, radiation oncologists, and oncologists. Patients with noninvasive UC or carcinoma in situ of the prostatic urethra and prostatic ducts can be treated with a urethra-sparing approach with transurethral resection and bacillus Calmette-Guérin (BCG). Cystoprostatectomy with extended pelvic lymphadenectomy should be reserved for patients not responding to BCG or as a primary treatment option in patients with extensive ductal or stromal involvement. CONCLUSIONS The 2013 guidelines document on primary UC is the first publication on this topic by the EAU. It aims to increase awareness in the urologic community and provide scientific transparency to improve outcomes of this rare urogenital malignancy.