Intravesical radiofrequency-induced hyperthermia combined with chemotherapy for non-muscle-invasive bladder cancer.

Although many treatment modalities and schedules for non-muscle-invasive bladder cancer (NMIBC) exist, all yet prove to have limitations. Therefore the search for new forms of therapy continues. One of these forms consists of combining intravesical chemotherapy, typically mitomycin C (MMC), with hyperthermia achieved by a microwave-applicator. We aimed to review the current status of intravesical radiofrequency (RF) induced chemohyperthermia (CHT) for NMIBC with regard to efficacy, adverse-events (AEs) and its future perspective. A search for RF-induced CHT in MEDLINE, Embase, Cochrane and ClinicalTrials.gov databases was performed. Relevant conference abstracts were searched for manually. If applicable, experts on the area were consulted. Papers were selected based on abstract and title. A table of newly published clinical trials since 2011 was constructed. No meta-analysis could be performed based on these new papers. Efficacy proved to be better for RF-induced CHT compared to both MMC alone and bacillus Calmette-Guérin (BCG) instillations, with the latter being based on just one abstract of a randomised controlled trial. The AE rate in CHT is higher compared to MMC instillation, but is similar compared to BCG, albeit different in the type of AE. In almost all studies no severe AEs are reported. Although heterogeneity in methodology exists, RF-induced CHT seems promising. However, alternative methods of applying hyperthermia are starting to present their first results, imposing as effective options too. Intravesical RF-induced CHT may become an alternative for BCG instillation, and possibly for cystectomy, although further level 1 evidence is required for both reliable and reproducible data on efficacy and adverse events.

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.

Transurethral Resection of Bladder Tumour: The Neglected Procedure in the Technology Race in Bladder Cancer.

Transurethral resection of bladder tumour is the initial, most critical step in the management of bladder cancer; as such, this is a call to arms for the urological community to it the due diligence it deserves regarding technology and training.

68Ga-Prostate-Specific Membrane Antigen Uptake in Gastrointestinal Stromal Tumor.

A 62-year-old man with recently diagnosed prostatic adenocarcinoma was referred for a whole-body Ga-prostate-specific membrane antigen (PSMA) PET/CT scan for staging. Although the scan did not reveal metastatic disease, it did reveal a PSMA-avid lesion in the upper abdomen located between the liver and the stomach. Histopathologic examination demonstrated a gastrointestinal stromal tumor. The lesion demonstrated increased uptake in the margins of the tumor with a central photopenic area, which we consider to be the typical pattern on PSMA images of a gastrointestinal stromal tumor, based on theoretical PSMA distribution in such a tumor and other reported cases.

Perioperative chemotherapy in muscle-invasive bladder cancer: overview and the unmet clinical need for alternative adjuvant therapy as studied in the MAGNOLIA trial.

The European Association of Urology Research Foundation has proposed that alternatives to perioperative chemotherapy should be evaluated. The MAGNOLIA study represents a unique opportunity to investigate the concept of immunotherapy in muscle-invasive bladder cancer.

Prognostic factors for survival in patients with recurrence of muscle invasive bladder cancer after treatment with curative intent.

UNLABELLED: Prognostic factors for survival after recurrent MIBC are unknown and were evaluated using a population-based series of 1409 MIBC patients. 330 Patients who underwent RC or RT with curative intent and who suffered from recurrence were selected. Multivariable survival analyses were performed. Clinicopathological factors that predict survival after recurrence are recurrence location, treatment for recurrence and age at recurrence diagnosis. PURPOSE: We conducted this study to evaluate the prognostic factors for survival among patients with recurrent muscle-invasive bladder cancer (MIBC) after initial treatment with curative intent. PATIENTS AND METHODS: Clinical data were collected from a population-based series of 1409 patients with MIBC. We selected 330 patients who underwent radical cystectomy (RC) or radiotherapy (RT) for urothelial carcinoma with curative intent and who experienced recurrence. Multivariate survival analyses were performed with death from MIBC as the endpoint. Covariates were gender, time to recurrence, age at diagnosis of recurrence, recurrence multiplicity, localization, and treatment for recurrence. Analyses were performed separately for patients initially treated with RC (i-RC) or external beam radiotherapy (i-EBRT). RESULTS: Patients with recurrence after i-RC showed a 1- and 3-year survival of 17% and 6%, respectively. Localization and treatment for recurrence were significantly associated with survival. Patients with recurrence after i-EBRT showed a 1- and 3-year survival of 31% and 12%, respectively. Age at diagnosis of recurrence, localization, and treatment for recurrence were significantly associated with survival. CONCLUSION: This study confirms the extremely poor prognosis after recurrence of MIBC in patients initially treated with surgery or RT. Clinicopathologic factors that predict survival after disease recurrence are location of recurrence, treatment for recurrence, and age at diagnosis of recurrence. Improved diagnosis of primary MIBC to detect extravesical disease and more effective therapeutic approaches to target recurrent MIBC are needed.

The role of bacillus Calmette-Guérin in the treatment of non-muscle-invasive bladder cancer.

CONTEXT: Bacillus Calmette-Guérin (BCG) remains the most effective intravesical treatment for non-muscle-invasive bladder cancer (NMIBC), but the clinical development of BCG has been accompanied by controversy. Recent publications have called into question a number of aspects related to its use. OBJECTIVE: To review the current clinical role of BCG in NMIBC, focusing on efficacy and tolerability as primary objectives and on strategies to predict response and decrease toxicity as secondary objectives. EVIDENCE ACQUISITION: We performed a systematic literature search of published articles in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases for the period from 1976 to November 2008. The following "free text" combination was used in the first instance: "BCG and intravesical and bladder cancer." Further free text searches were performed by separately adding the following keywords to the combination "BCG and intravesical": survival, progression, recurrence, maintenance, dosing, toxicity, tolerability, side effects, prognostic factors. EVIDENCE SYNTHESIS: BCG is the most effective intravesical agent for preventing NMIBC recurrence, but its role in disease progression remains controversial. In intermediate-risk NMIBC, the superiority of BCG over chemotherapy is well established for disease recurrence but not for progression and needs to be balanced against higher toxicity. With regard to high-risk NMIBC, there is sufficient evidence to show that BCG is the most effective treatment of carcinoma in situ for ablation, disease-free interval, and progression, but the impact of BCG on the natural history of T1G3 tumors relies on a low level of evidence. Maintenance remains crucial for efficacy. The dose can be safely and effectively reduced to decrease its toxicity, which is slightly greater than chemotherapy. CONCLUSIONS: BCG should still be viewed as the most effective intravesical agent, but its role in the progression of papillary tumors needs to be clarified. BCG remains an alternative to intravesical chemotherapy in intermediate-risk NMIBC, and it is recommended as the standard of care for high-risk NMIBC.

Effects of cognitive behavior therapy in severely fatigued disease-free cancer patients compared with patients waiting for cognitive behavior therapy: a randomized controlled trial.

PURPOSE: Persistent fatigue is a long-term adverse effect experienced by 30% to 40% of patients cured of cancer. The main objective of this randomized controlled trial was to show the effectiveness of cognitive behavior therapy (CBT) especially designed for fatigue in cancer survivors. PATIENTS AND METHODS: A total of 112 cancer survivors with somatically unexplained fatigue were allocated randomly to immediate cognitive behavior therapy or to a waiting list condition for therapy. Both conditions were assessed two times, at baseline and 6 months later. The primary outcome variables were fatigue severity (Checklist Individual Strength) and functional impairment (Sickness Impact Profile). Data were analyzed by intention to treat. RESULTS: Analyses were based on 50 patients in the intervention condition and 48 patients in the waiting list condition. Patients in the intervention condition reported a significantly greater decrease than patients in the waiting list condition in fatigue severity (difference, 13.3; 95% CI, 8.6 to 18.1) and in functional impairment (difference, 383.2; 95% CI, 197.1 to 569.2). Clinically significant improvement for the CBT group compared with the waiting list group was seen in fatigue severity (54% v 4% of the patients, respectively) and in functional impairment (50% v 18% of the patients, respectively). CONCLUSION: Cognitive behavior therapy has a clinically relevant effect in reducing fatigue and functional impairments in cancer survivors.

Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study.

PURPOSE: We determined if improved tumor detection using hexaminolevulinate (HAL) fluorescence cystoscopy could lead to improved treatment in patients with bladder cancer. MATERIALS AND METHODS: A total of 146 patients with known or suspected bladder cancer were assessed in this open, comparative, within patient, controlled phase III study. Patients received intravesical HAL for 1 hour and were assessed with standard white light cystoscopy and blue light fluorescence cystoscopy. All lesions were mapped onto a bladder chart and biopsies were taken from suspicious areas for assessment by an independent pathologist. An independent urologist blinded to the detection method used recommended treatment plans based on biopsy results and medical history according to European Association of Urology bladder cancer guidelines. Any differences in recommended treatment plans arising from the 2 cystoscopy methods were recorded. RESULTS: HAL imaging improved overall tumor detection. Of all tumors 96% were detected with HAL imaging compared with 77% using standard cystoscopy. This difference was particularly noticeable for dysplasia (93% vs 48%), carcinoma in situ (95% vs 68%) and superficial papillary tumors (96% vs 85%). As a result of improved detection, additional postoperative procedures were recommended in 15 patients (10%) and more extensive treatment was done intraoperatively in a further 10. Overall 17% of patients received more appropriate treatment at the time of the study following blue light fluorescence cystoscopy, that is 22% or 1 of 5 if patients without tumors were excluded. CONCLUSIONS: HAL imaging is more effective than standard white light cystoscopy for detecting bladder tumors and lesions. This leads to improved treatment in a significant number of patients (p <0.0001).

Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy.

PURPOSE: In this European multicenter study we compared hexaminolevulinate (HAL) fluorescence cystoscopy and standard white light cystoscopy for the detection of carcinoma in situ (CIS) in patients suspected of having high risk bladder cancer. MATERIALS AND METHODS: This study was a prospective controlled, within-patient comparison of standard and HAL fluorescence cystoscopy. Eligible patients received an intravesical instillation of 50 ml HAL 8 mM solution. Cystoscopy was performed using a D light system, which provided white and blue light at 375 to 440 nm. The bladder wall was inspected and mapped, first under white light, followed by blue light. All tumors and suspicious areas identified under white light and by red fluorescence were resected or biopsied. Histological findings were assessed by an independent central pathologist blinded to the identity of the biopsies. RESULTS: Of 211 evaluable patients 83 (39%) had CIS, of whom 18 (22%) were detected by HAL cystoscopy only, 62 (75%) were detected by standard and HAL cystoscopy, 2 (2%) were detected by standard cystoscopy only and 1 (1%) was detected by nonguided biopsy. Therefore, HAL cystoscopy identified 28% more patients with CIS than standard cystoscopy. The side effects of HAL instillation were negligible and no unexpected events were reported. CONCLUSIONS: HAL fluorescence cystoscopy improves the detection of bladder CIS significantly, which has consequences for clinical management and may improve the patient prognosis. The procedure is easily implemented as an adjunct to standard cystoscopy and it adds no significant risk of complications.