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.

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.

An editor's considerations in publishing industry-sponsored studies.

The fundamental responsibility of a journal editor is to assure that studies accepted for publication provide rigorous original scientific information and reviews that are considered important to the readership. The fundamental requirements of such reports from an editor's perspective include objectivity and transparency in each of the study design, implementation of investigation methods, acquisition of data, inclusive analysis and interpretation of results, appropriate application of statistical methods, presentation of outcomes in the context of a balanced and comprehensive review of relevant literature, and meaningful conclusions. In proceeding on these presumptions, editors then have the responsibility of obtaining rigorous, objective, and constructive reviews of these reports so that they can make an unbiased decision regarding their disposition. The fundamental objective in this is to enhance the ultimate scientific validity and value of the work if and when it is accepted for publication. Guidelines have been advanced by several organizations to identify how such editorial responsibilities can be fulfilled. These guidelines also pertain to investigators, authors, and sponsors of the studies, which the various reports and reviews describe. The present article reviews these guidelines as they relate to both industry-sponsored and investigator-initiated investigations and as relevant to the variety of reports that a scientific/medical journal such as Urologic Oncology: Seminars and Original Investigations receives for publication.

Micropapillary bladder cancer: current treatment patterns and review of the literature.

OBJECTIVES: No guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature. MATERIALS AND METHODS: A survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network-sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review. RESULTS: Most survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease. CONCLUSIONS: The management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC.

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.

Neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: which patients benefit?

Level I evidence supports neoadjuvant chemotherapy in the treatment of advanced bladder cancer. For the most benefit, it is suggested that neoadjuvant chemotherapy be restricted to patients with clinical T3 disease and/or clinical N+ disease.

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.