Development and evaluation of a bladder Cancer specific survivorship care plan by patients and clinical care providers: a multi-methods approach.

BACKGROUND, CONTEXT AND PURPOSE: In spite of the mixed evidence for their impact, survivorship Care Plans (SCPs) are recommended to enhance quality of care for cancer survivors. Data on the feasibility of SCPs in bladder cancer (BC) is sparse. Using a mixed-methods approach, this study describes the iterative development, acceptability and feasibility of BC specific SCP (BC-SCP) in clinical settings. METHODS: In Phase I, we developed the BC-SCP. In Phase II, we conducted four focus groups with 19 patients and 15 providers to examine its acceptability and usability challenges. Data analyses using the Atlas.ti program, informed refinement of the BC-SCP. In Phase III, we conducted feasibility testing of the refined BC-SCP with 18 providers from 12 health-centers. An encounter survey was completed after each assessment to examine the feasibility of the BC-SCP. Chi-square and Fisher Exact tests were used for comparative analyses. RESULTS: During phase I, we observed high patient and provider acceptability of the BC-SCP and substantial engagement in improving its content, design, and structure. In Phase II, providers completed 59 BC-SCPs. Mean time for BC-SCP completion was 12.3 min. Providers reported that BC-SCP content was clear, did not hamper clinic flow and was readily completed with easy-to-access information. Comparative analyses to examine differences in SCP completion time by patient clinico-demographic characteristics and provider type revealed no significant differences. CONCLUSIONS: Our BC-SCP has clinical relevance, and can be used in an active practice setting. However, considerable progress will be necessary to achieve implementation of and sharing the BC-SCP with patients and care providers, particularly within the electronic medical record. In summary, BC-SCPs are essential to improve the follow up care of BC survivors. Clinical resources are required to ensure appropriate implementation of BC-SCPs. TRIAL REGISTRATION: Study HUM00056082.

An up-to-date catalog of available urinary biomarkers for the surveillance of non-muscle invasive bladder cancer.

OBJECTIVES: With the advent of novel genomic and transcriptomic technologies, new urinary biomarkers have been identified and tested for bladder cancer (BCa) surveillance. To summarize the current status of urinary biomarkers for the detection of recurrence and/or progression in the follow-up of non-muscle invasive BCa patients, and to assess the value of urinary biomarkers in predicting response to intravesical Bacillus Calmette-Guerin (BCG) therapy. METHODS AND MATERIALS: A medline/pubmed© literature search was performed. The performance of commercially available and investigational biomarkers has been reviewed. End points were cancer detection (recurrence), cancer progression, and response to BCG therapy. RESULTS: The performance requirements for biomarkers are variable according to the clinical scenario. The clinical role of urinary biomarkers in the follow-up of non-muscle invasive BCa patients remains undefined. The FDA-approved tests provide unsatisfactory sensitivity and specificity levels and their use is limited. Fluorescence in situ hybridization (FISH) has been shown to be useful in specific scenarios, mostly as a reflex test and in the setting of equivocal urinary cytology. FISH and immunocytology could conceivably be used to assess BCG response. Recently developed biomarkers have shown promising results; upcoming large trials will test their utility in specific clinical scenarios in a manner similar to a phased drug development strategy. CONCLUSIONS: Current commercially available urinary biomarker-based tests are not sufficiently validated to be widely used in clinical practice. Several novel biomarkers are currently under investigation. Prospective multicenter analyses will be needed to establish their clinical relevance and value.

Molecular markers for bladder cancer screening, early diagnosis, and surveillance: the WHO/ICUD consensus.

Due to the lack of disease-specific symptoms, diagnosis and follow-up of bladder cancer has remained a challenge to the urologic community. Cystoscopy, commonly accepted as a gold standard for the detection of bladder cancer, is invasive and relatively expensive, while urine cytology is of limited value specifically in low-grade disease. Over the last decades, numerous molecular assays for the diagnosis of urothelial cancer have been developed and investigated with regard to their clinical use. However, although all of these assays have been shown to have superior sensitivity as compared to urine cytology, none of them has been included in clinical guidelines. The key reason for this situation is that none of the assays has been included into clinical decision-making so far. We reviewed the current status and performance of modern molecular urine tests following systematic analysis of the value and limitations of commercially available assays. Despite considerable advances in recent years, the authors feel that at this stage the added value of molecular markers for the diagnosis of urothelial tumors has not yet been identified. Current data suggest that some of these markers may have the potential to play a role in screening and surveillance of bladder cancer. Well-designed protocols and prospective, controlled trials will be needed to provide the basis to determine whether integration of molecular markers into clinical decision-making will be of value in the future.

Pathological T0 following radical cystectomy with or without neoadjuvant chemotherapy: a useful surrogate.

PURPOSE: Several large, randomized, controlled trials provide evidence that neoadjuvant chemotherapy improves the outcome of radical cystectomy for muscle invasive urothelial bladder cancer. We analyzed the designs, methods and observations of these trials to identify patient subgroups that appeared most likely to benefit. We also identified distinguishing features compared to groups that did not achieve improved outcomes. MATERIALS AND METHODS: We analyzed initial and updated methods and results of the 4 main prospective trials of neoadjuvant chemotherapy (SWOG, Medical Research Council, and Nordic I and II) and subsequent meta-analyses. These series are the basis for advocating neoadjuvant chemotherapy in all patients with muscle invasive urothelial bladder cancer who undergo radical cystectomy. RESULTS: The greatest apparent benefit was seen in patients free of cancer at radical cystectomy (pT0). They had markedly improved overall and disease specific survival compared to patients with residual disease. However, improvements occurred regardless of whether there was down-staging from muscle invasive urothelial bladder cancer to pT0 after transurethral resection alone (controls) or after resection plus neoadjuvant chemotherapy. Thus, the major benefit of chemotherapy appeared to be that more patients achieved pT0. We also explored the study limitations that may have influenced outcomes and considered the potential for overtreatment in patients not likely to benefit from chemotherapy. Finally, we used risk stratification to create a decision tree model for selecting patients for neoadjuvant chemotherapy that could conceivably maximize oncologic outcome and minimize overtreatment. CONCLUSIONS: Patients with pT0 in the 4 main neoadjuvant chemotherapy trials and their subsequent meta-analyses experienced similar survival, far exceeding that in groups that did not achieve pT0. The benefit of neoadjuvant chemotherapy appears to be the larger number of cases than in the transurethral resection only group that were down-staged to pT0, suggesting that variables other than chemotherapy may have influenced outcomes. Therefore, strategies to selectively administer neoadjuvant chemotherapy to certain patients at risk have the potential to maintain improved bladder cancer outcomes while reducing overtreatment and its associated toxicity.

25 years International Bladder Cancer Network (IBCN): The past, the present, and the future.

In 1997 an international group of scientists organized a meeting in Barcelona, Spain, to discuss the use of biomarkers in the management of patients with bladder cancer. This meeting was the offspring of an - initially informal - group that finally resulted in the foundation and incorporation of the International Bladder Cancer Network (IBCN) e.V. in 2005. Over the years the group has supported several research initiatives and generated several recommendations on the use of biomarkers in the diagnosis and treatment of bladder cancer. Meeting quality was generated by inviting experts presenting state-of-the-art lectures or work in progress reports, interdisciplinarity and the limited number of participants supporting an open and personal exchange resulted in a format increasingly attracting participants from all over the world. The recent limitations caused by the Covid-19 pandemic were partially met by organizing several well attended webinars. The future challenge is to maintain the IBCN meeting spirit despite an increasing interest of the scientific community and industrial partners to participate. However, the integration of and interaction between increasingly more specialized disciplines is a challenge that can be better catalyzed by an international multidisciplinary network than mostly national professional associations.

New optical imaging technologies for bladder cancer: considerations and perspectives.

PURPOSE: Bladder cancer presents as a spectrum of different diatheses. Accurate assessment for individualized treatment depends on initial diagnostic accuracy. Detection relies on white light cystoscopy accuracy and comprehensiveness. Aside from invasiveness and potential risks, white light cystoscopy shortcomings include difficult flat lesion detection, precise tumor delineation to enable complete resection, inflammation and malignancy differentiation, and grade and stage determination. Each shortcoming depends on surgeon ability and experience with the technology available for visualization and resection. Fluorescence cystoscopy/photodynamic diagnosis, narrow band imaging, confocal laser endomicroscopy and optical coherence tomography address the limitations and have in vivo feasibility. They detect suspicious lesions (photodynamic diagnosis and narrow band imaging) and further characterize lesions (optical coherence tomography and confocal laser endomicroscopy). We analyzed the added value of each technology beyond white light cystoscopy and evaluated their maturity to alter the cancer course. MATERIALS AND METHODS: Detailed PubMed® searches were done using the terms "fluorescence cystoscopy," "photodynamic diagnosis," "narrow band imaging," "optical coherence tomography" and "confocal laser endomicroscopy" with "optical imaging," "bladder cancer" and "urothelial carcinoma." Diagnostic accuracy reports and all prospective studies were selected for analysis. We explored technological principles, preclinical and clinical evidence supporting nonmuscle invasive bladder cancer detection and characterization, and whether improved sensitivity vs specificity translates into improved correlation of diagnostic accuracy with recurrence and progression. Emerging preclinical technologies with potential application were reviewed. RESULTS: Photodynamic diagnosis and narrow band imaging improve nonmuscle invasive bladder cancer detection, including carcinoma in situ. Photodynamic diagnosis identifies more papillary lesions than white light cystoscopy, enabling more complete resection and fewer residual tumors. Despite improved treatment current data on photodynamic diagnosis do not support improved high risk diathetic detection and characterization or correlation with disease progression. Prospective recurrence data are lacking on narrow band imaging. Confocal laser endomicroscopy and optical coherence tomography potentially grade and stage lesions but data are lacking on diagnostic accuracy. Several emerging preclinical technologies may enhance the diagnostic capability of endoscopic imaging. CONCLUSIONS: New optical imaging technologies may improve bladder cancer detection and characterization, and transurethral resection quality. While data on photodynamic diagnosis are strongest, the clinical effectiveness of these technologies is not proven. Prospective studies are needed, particularly of narrow band imaging, confocal laser endomicroscopy and optical coherence tomography. As each technology matures and new ones emerge, cost-effectiveness analysis must be addressed in the context of the various bladder cancer types.

Do Gleason patterns 3 and 4 prostate cancer represent separate disease states?

PURPOSE: The Gleason scoring system has been the traditional basis for studies on the assessment and treatment of prostate cancer. Recent reports of long-term prostate cancer outcomes stratified by Gleason score based on the 2005 ISUP (International Society of Urological Pathology) update suggest that important aspects of the biology of prostate cancer correlate with commonly available histopathological information. In this review we present a conceptual framework for the possible existence of distinct but interrelated developmental pathways in the context of the Gleason score in considering various biological and clinical aspects of prostate cancer. This may be useful in characterizing prostate cancer as an indolent condition in some and an aggressive disease in others, in decision making for treatment, and in the interpretation of the biological course and treatment outcomes. MATERIALS AND METHODS: A comprehensive review of clinical, pathological and investigational biological literature on this topic was conducted. In addition, the biological behavior of prostate cancer as interpreted from this survey was compared to that of other solid neoplasms in developing a schema for characterizing the pathogenesis of various forms of the disease. RESULTS: The Gleason scoring system has been found to have fundamental value in predicting the behavior of prostate cancer and assessing outcomes of its treatment. Increasingly, the proportion of Gleason pattern 4 in a prostatectomy specimen is being recognized as a critical factor in predicting the rates of biochemical recurrence and prostate cancer specific mortality. Under the current Gleason classification, a Gleason 3 + 3 = 6 cancer carries a minimal long-term risk of progression or mortality. Risk of biochemical recurrence and prostate cancer specific mortality increases with increasing proportions of the Gleason 4 component in the prostatectomy specimen, from 3 + 3 = 6 with tertiary 4 (ie less than 5% of a 4 component) to 3 + 4 = 7, 4 + 3 = 7 and 4 + 4 = 8. Assuming that the Gleason 4 component increases in volume more rapidly with time than well differentiated components, it can be inferred that a smaller proportion of Gleason 4 could mean that the cancer has been identified at an earlier phase in the natural history of the disease. This could explain the improved prognosis on the basis of length and lead time biases, and conceivably on the basis of a decreased likelihood of cancer cells having metastasized. Correspondingly, increasing amounts of Gleason 4 cancer in a prostate specimen might be explained in 2 ways, as the preferential growth of a single clone of Gleason 4 cells, possibly with intraprostatic spread, or the evolution of Gleason 3 cancer cells to become Gleason 4. These hypotheses have been examined by genetic analysis of metastatic deposits and by comparisons of multiple foci of cancer within individual prostates. The clinical significance of these concepts in regard to disease status at diagnosis, treatment selection, outcomes of treatment, and implications for future research on the basis of clinical and molecular observations are the basis of the developmental schemata we propose. CONCLUSIONS: Given the relatively benign nature of homogeneous, low volume Gleason 3 tumors, and the progressive risk of biochemical recurrence and prostate cancer specific mortality with increasing quantities of Gleason 4 components, we propose that Gleason 4 (and 5) cancers constitute cancer diatheses distinct from that of Gleason 3 cancer. This distinction may contribute to the understanding of the prognosis intrinsic to these biological behavioral patterns, and help guide the translation of findings at molecular and histological levels to a more precise selection of treatments.

Urologic Oncology: Seminars and Original Investigations. A Twenty-Fifth Anniversary History.

This narrative reviews the history of Urologic Oncology: Seminars and Original Investigations from its inception and founding through its development to reach its current status. It describes the difficulties it experienced during its initial years when it almost folded, its resuscitation when it was designated as the "official journal" of the Society of Urologic Oncology, its merger with Seminars in Urologic Oncology to strengthen the content of both journals in a new format, its acceptance for indexation by the National Library of Medicine, its progress to monthly publication in addressing the needs of both authors and readership, and its current status as a leading multidisciplinary journal in urologic oncology. As a founding editor and managing editor for the first 5 years and then as editor-in-chief for the next 20 years, the author has been integrally involved in each step of the Journal's development and maturation. The Journal has been referred to as "the journal that almost never was" as it now has reached its 25th year of publication. This article commemorates the Journal's 25th Anniversary and gratefully acknowledges all of those investigators, authors, reviewers, editors, publishers and the readership who have contributed to the Journal's ongoing success.

A history of the Society of Urologic Oncology.

This narrative of the history of the Society of Urologic Oncology (SUO) presents the story of the founding and development of this organization and the creation and establishment of its initiatives and programs. It includes a description of how "Urologic Oncology: Seminars and Original Investigations" came to be designated as its "official journal", thus commemorating the anniversary of the Journal's twenty-five years of publication.

The effect of age and gender on bladder cancer: a critical review of the literature.

While patient age and gender are important factors in the clinical decision-making for treating urothelial carcinoma of the bladder (UCB), there are no evidence-based recommendations to guide healthcare professionals. We review previous reports on the influence of age and gender on the incidence, biology, mortality and treatment of UCB. Using MEDLINE, we searched for previous reports published between January 1966 and July 2009. While men are three to four times more likely to develop UCB than women, women present with more advanced disease and have worse survival rates. The disparity among genders is proposed to be the result of a differential exposure to carcinogens (i.e. tobacco and chemicals) as well as reflecting genetic, anatomical, hormonal, societal and environmental factors. Inpatient length of stay, referral patterns for haematuria and surgical outcomes suggest that inferior quality of care for women might be an additional cause of gender inequalities. Age is the greatest single risk factor for developing UCB and dying from it once diagnosed. Elderly patients face both clinical and institutional barriers to appropriate treatment; they receive less aggressive treatment and sub-therapeutic dosing. Much evidence suggests that chronological age alone is an inadequate indicator in determining the clinical and behavioural response of older patients to UCB and its treatment. Epidemiological and mechanistic molecular studies should be encouraged to design, analyse and report gender- and age-specific associations. Improved bladder cancer awareness in the lay and medical communities, careful patient selection, treatment tailored to the needs and the physiological and physical reserve of the individual patient, and proactive postoperative care are particularly important. We must strive to develop transdisciplinary collaborative efforts to provide tailored gender- and age-specific care for patients with UCB.

Advanced patient age is associated with inferior cancer-specific survival after radical nephroureterectomy.

OBJECTIVE: To assess the impact of patient age on outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Data were collected on 1453 patients treated with RNU at 13 centres. Pathological slides were reviewed by dedicated genitourinary pathologists according to standardized criteria. Age at RNU was analysed both as a continuous and categorical variable (<50, n = 85; 50-59.9, n = 229; 60-69.9, n = 416; 70-79.9, n = 523; > or =80 years, n = 200). RESULTS Patients aged <50 years were less likely to have undergone previous ureteroscopy and to have a history of bladder cancer (P < or = 0.026). Advanced age was associated with infiltrative architecture and female gender (P < or = 0.003). Patients aged >70 years were less likely to undergo lymphadenectomy and to receive adjuvant chemotherapy (P < or = 0.026). In multivariable analyses, being older was associated with decreased all-cause (AC) survival (>60 years) and cancer-specific survival (CSS; >80 years) after controlling for the effects of standard pathological features (P < or = 0.006). However, addition of age did not improve the predictive accuracy of a base model that included standard pathological features for prediction of either disease recurrence, AC survival or CSS. CONCLUSIONS: Being older at the time of RNU was associated with decreased survival. This finding could be due to a change in the biological potential of the tumour cell, a decrease in the host's defence mechanisms, or differences in care patterns. Further work is needed to improve our understanding of UTUC outcomes in this growing segment of the population and to develop strategies to improve cancer control in the elderly.

Screening for bladder cancer: theoretical and practical issues in considering the treated and untreated natural history of the various forms of the disease.

Screening is used to detect disease earlier in its course, allow earlier treatment, and presumably decrease morbidities and potential mortality associated with the later expression of more advanced disease and presumably more complex treatments consequently required. Judicious screening in bladder cancer depends on an understanding of how the different forms of bladder cancer express their biological potential, whether the tools available for screening have sufficient sensitivity and specificity to have accurate predictive value in accurately diagnosing and assessing each cancer diathesis earlier in its course, and how this may influence the morbidities and mortality associated with each. The principles of screening, potential biases that can affect their accuracy and the interpretation of outcomes, tools currently available for screening, their efficacies and pitfalls, and lessons learned from studies of the role of screening in prostate cancer will be reviewed to offer an understanding of the potential role that screening may play in the different forms of bladder cancer in the context of their preclinical and treated natural history.

Bladder cancer: chemoprevention, complementary approaches and budgetary considerations.

Bladder cancer results from complex and only partially understood host-environmental interactions. Tobacco smoking is the greatest risk factor for bladder cancer, but the actual risk to an individual reflects not only the amount of exposure to the carcinogens in tobacco smoke but also host susceptibility to these carcinogens and possibly other factors. Lifestyle may have a significant effect on the incidence of this disease. The forms of chemoprevention and their relevance to bladder cancer, the impact of lifestyle and complementary medicine, and the costs of diagnosing and treating bladder cancer are reviewed to provide a base for advances in decreasing the incidence, recurrence and costs of this disease.