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OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS). PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups. RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints. CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. RESULTS AND LIMITATIONS: Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. CONCLUSIONS: We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. PATIENT SUMMARY: As there is currently a BCG shortage, informa

Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

In many patients with prostate cancer, androgen deprivation therapy (ADT) is administered over prolonged periods of time. The benefits of long-term ADT in patients with advanced disease are well established and, more recently, studies have shown that long-term adjuvant ADT used in combination with radiotherapy improves survival in patients with earlier stages of disease. Nevertheless, clinicians should remain aware of the potential long-term side effects of ADT and the strategies that can be used to manage or prevent long-term complications. One such strategy is intermittent androgen deprivation (IAD), in which patients receive cycles of ADT, the duration of which is usually determined by PSA levels. Accumulating data indicate that this approach improves the tolerability of ADT (particularly sexual dysfunction) and patients ' quality of life, without compromising clinical outcomes (progression and survival). Indeed, the latest European Association of Urology guidelines state that IAD should no longer be considered investigational. Nevertheless, some questions remain unanswered, including: who are the most suitable patients for IAD and what are the optimal PSA levels for stopping and restarting treatment? Osteoporosis (and the resultant increased risk of fractures) is a well-recognized complication of long-term ADT. Bone mineral density should be measured before and during long-term ADT and patients advised to make appropriate lifestyle changes to help preserve bone health. Pharmacological intervention is also an option. Denosumab (an NF-κB ligand inhibitor) significantly reduces ADT-induced bone loss and the risk of fractures in patients with non-metastatic disease. In those whose disease has metastasized, zoledronate and denosumab are licensed to prevent skeletal-related events and a large randomized study has shown that denosumab is more effective than zoledronate in this setting. © 2012 The Authors BJU International © 2012 BJU International., SCOPUS: re.j, FLWIN, info:eu-repo/semantics/published

Context: Serum testosterone measurement has no widely accepted place in the management of patients with prostate cancer (PCa). However, several potential clinical applications of serum testosterone determination can be envisaged. Objective: To review the role of testosterone and the androgen axis in the natural history of PCa and evaluate the evidence for the clinical application of serum testosterone measurement in patient screening, diagnosis, and management. Evidence acquisition: A Medline search retrieved original research and review articles relating to the androgen axis in PCa and the use of testosterone measurement for (1) assessing PCa risk in the general population, (2) adding to the specificity of prostate-specific antigen (PSA) testing, (3) determining tumour aggressiveness, (4) assessing the efficacy of androgen-deprivation therapy (ADT), and (5) optimising the scheduling of intermittent ADT. Relevant data were reviewed during a roundtable discussion, and consensus recommendations were agreed. Evidence synthesis: A body of data implicates the androgen axis in PCa throughout its natural history. Based on current evidence, serum testosterone measurement cannot be recommended for determining PCa risk, increasing specificity of PSA testing, or assessing tumour aggressiveness. In contrast, for patients receiving ADT, there is a clear rationale for serum testosterone monitoring to ensure that castration levels are achieved. Practical recommendations for testosterone measurement during ADT are outlined. If PSA is rising while on ADT, castration levels of serum testosterone must be demonstrated before hormonal independence can be assumed. Serum testosterone levels might be considered an additional trigger for therapy reinitiation in intermittent ADT schedules. Finally, future prospective studies should further evaluate the potential relevance of testosterone measurement as an independent assessment of prognosis and treatment decision in different disease stages., SCOPUS: re.j, info:eu-repo/semantics/published

Context: Androgen-deprivation therapy (ADT) is the mainstay of treatment for metastatic prostate cancer and is also recommended in association with external-beam radiation therapy (EBRT) for patients with high-risk disease. Objective: Our aim was to make recommendations regarding optimal timing of ADT, target serum testosterone levels, intermittent ADT delivery, and quality of life (QoL) during ADT. Evidence acquisition: This review contains recommendations from a European expert panel held in May 2009. Evidence synthesis: There is ongoing debate over whether ADT should be initiated at diagnosis or delayed until biochemical or symptomatic progression. Immediate ADT is recommended for metastatic disease to defer symptom development and reduce serious complications. In node-positive disease or high-risk nonmetastatic disease unfit for curative therapy, immediate ADT is also an option. Furthermore, there is a clear benefit of adjuvant ADT in association with EBRT in patients with high-risk disease. Some retrospective evidence also supports adjuvant ADT use following radical prostatectomy for high-risk localised disease. In cases of biochemical relapse after definitive local therapy, early ADT may benefit patients with poor prognostic factors. For patients on ADT, the traditional <50. ng/dl target for serum testosterone levels should be considered outdated. It is now clear that a <20. ng/dl threshold better reflects the outcome of bilateral orchidectomy, which is considered the standard of reference in ADT. Recent data demonstrate a clinical benefit of testosterone reduction to more stringent targets than the historical <50. ng/dl threshold. In addition, emerging evidence suggests that intermittent scheduling of ADT can reduce adverse events and improve QoL without compromising survival, but further data are needed to guide its clinical use. Finally, adverse events of ADT may affect QoL and must be discussed with patients. Conclusions: Based on current evidence, the pan, SCOPUS: re.j, info:eu-repo/semantics/published

Context: Serum testosterone measurement has no widely accepted place in the management of patients with prostate cancer (PCa). However, several potential clinical applications of serum testosterone determination can be envisaged. Objective: To review the role of testosterone and the androgen axis in the natural history of PCa and evaluate the evidence for the clinical application of serum testosterone measurement in patient screening, diagnosis, and management. Evidence acquisition: A Medline search retrieved original research and review articles relating to the androgen axis in PCa and the use of testosterone measurement for (1) assessing PCa risk in the general population, (2) adding to the specificity of prostate-specific antigen (PSA) testing, (3) determining tumour aggressiveness, (4) assessing the efficacy of androgen-deprivation therapy (ADT), and (5) optimising the scheduling of intermittent ADT. Relevant data were reviewed during a roundtable discussion, and consensus recommendations were agreed. Evidence synthesis: A body of data implicates the androgen axis in PCa throughout its natural history. Based on current evidence, serum testosterone measurement cannot be recommended for determining PCa risk, increasing specificity of PSA testing, or assessing tumour aggressiveness. In contrast, for patients receiving ADT, there is a clear rationale for serum testosterone monitoring to ensure that castration levels are achieved. Practical recommendations for testosterone measurement during ADT are outlined. If PSA is rising while on ADT, castration levels of serum testosterone must be demonstrated before hormonal independence can be assumed. Serum testosterone levels might be considered an additional trigger for therapy reinitiation in intermittent ADT schedules. Finally, future prospective studies should further evaluate the potential relevance of testosterone measurement as an independent assessment of prognosis and treatment decision in different disease stages., SCOPUS: re.j, info:eu-repo/semantics/published

Context: Androgen-deprivation therapy (ADT) is the mainstay of treatment for metastatic prostate cancer and is also recommended in association with external-beam radiation therapy (EBRT) for patients with high-risk disease. Objective: Our aim was to make recommendations regarding optimal timing of ADT, target serum testosterone levels, intermittent ADT delivery, and quality of life (QoL) during ADT. Evidence acquisition: This review contains recommendations from a European expert panel held in May 2009. Evidence synthesis: There is ongoing debate over whether ADT should be initiated at diagnosis or delayed until biochemical or symptomatic progression. Immediate ADT is recommended for metastatic disease to defer symptom development and reduce serious complications. In node-positive disease or high-risk nonmetastatic disease unfit for curative therapy, immediate ADT is also an option. Furthermore, there is a clear benefit of adjuvant ADT in association with EBRT in patients with high-risk disease. Some retrospective evidence also supports adjuvant ADT use following radical prostatectomy for high-risk localised disease. In cases of biochemical relapse after definitive local therapy, early ADT may benefit patients with poor prognostic factors. For patients on ADT, the traditional <50. ng/dl target for serum testosterone levels should be considered outdated. It is now clear that a <20. ng/dl threshold better reflects the outcome of bilateral orchidectomy, which is considered the standard of reference in ADT. Recent data demonstrate a clinical benefit of testosterone reduction to more stringent targets than the historical <50. ng/dl threshold. In addition, emerging evidence suggests that intermittent scheduling of ADT can reduce adverse events and improve QoL without compromising survival, but further data are needed to guide its clinical use. Finally, adverse events of ADT may affect QoL and must be discussed with patients. Conclusions: Based on current evidence, the pan, SCOPUS: re.j, info:eu-repo/semantics/published

Context: Although there is increasing interest in the use of neoadjuvant or adjuvant hormone therapy with local treatment for patients with prostate cancer (PCa), the survival benefit of hormone therapy is still debated. In addition, hormone therapy is associated with adverse events, which can have negative effects on a patient's quality of life (QoL). Intermittent hormone therapy is being investigated as an alternative to continuous hormone therapy for advanced PCa with the aims of delaying progression to hormone-refractory PCa and minimising adverse events. Objective: To summarise current controversies on hormone therapy for PCa. Evidence acquisition: This manuscript is based on presentations given at a satellite symposium held at the 2nd World Congress on Controversies in Urology (CURy) in Lisbon, Portugal. Recent English-language reports were identified through a search of Medline and abstracts of scientific congresses on hormone therapy for PCa. Data from review papers, original papers, and abstracts were compiled and interpreted. Evidence synthesis: Neoadjuvant hormone therapy with radical prostatectomy (RP) does not seem to offer a survival advantage over RP alone in patients with localised and locally advanced PCa. Neoadjuvant hormone therapy with radiotherapy (RT) appears to improve treatment outcomes over RT alone in patients with locally advanced PCa, but the impact on overall survival is still unclear. Adjuvant hormone therapy with RT seems to increase overall survival in high-risk localised and locally advanced PCa. Final results of a phase 3 trial suggest that intermittent hormone therapy improves QoL without a negative effect on overall survival compared with continuous hormone therapy. Furthermore, the patient-physician dialogue should be enhanced and patients' preferences should be taken into consideration in the decision-making process. Conclusions: Neoadjuvant or adjuvant hormone therapy with radical treatment may improve survival in carefully sel, SCOPUS: re.j, info:eu-repo/semantics/published

Context: Although there is increasing interest in the use of neoadjuvant or adjuvant hormone therapy with local treatment for patients with prostate cancer (PCa), the survival benefit of hormone therapy is still debated. In addition, hormone therapy is associated with adverse events, which can have negative effects on a patient's quality of life (QoL). Intermittent hormone therapy is being investigated as an alternative to continuous hormone therapy for advanced PCa with the aims of delaying progression to hormone-refractory PCa and minimising adverse events. Objective: To summarise current controversies on hormone therapy for PCa. Evidence acquisition: This manuscript is based on presentations given at a satellite symposium held at the 2nd World Congress on Controversies in Urology (CURy) in Lisbon, Portugal. Recent English-language reports were identified through a search of Medline and abstracts of scientific congresses on hormone therapy for PCa. Data from review papers, original papers, and abstracts were compiled and interpreted. Evidence synthesis: Neoadjuvant hormone therapy with radical prostatectomy (RP) does not seem to offer a survival advantage over RP alone in patients with localised and locally advanced PCa. Neoadjuvant hormone therapy with radiotherapy (RT) appears to improve treatment outcomes over RT alone in patients with locally advanced PCa, but the impact on overall survival is still unclear. Adjuvant hormone therapy with RT seems to increase overall survival in high-risk localised and locally advanced PCa. Final results of a phase 3 trial suggest that intermittent hormone therapy improves QoL without a negative effect on overall survival compared with continuous hormone therapy. Furthermore, the patient-physician dialogue should be enhanced and patients' preferences should be taken into consideration in the decision-making process. Conclusions: Neoadjuvant or adjuvant hormone therapy with radical treatment may improve survival in carefully sel, SCOPUS: re.j, info:eu-repo/semantics/published

Objectives: This report summarises major new findings in the field of prostate cancer (PCa) presented during the 2006 annual meetings of the European Association of Urology (EAU), American Urological Association (AUA), American Society of Clinical Oncology (ASCO), and the American Society for Therapeutic Radiology and Oncology (ASTRO). Methods: Urologic experts in the field of PCa selected relevant new findings that were discussed during a closed meeting in September 2006. The key points are communicated in this paper. Results: There was much discussion about the relevance of Prostate-Specific Antigen (PSA) screening. There seems to be no specific threshold for early detection of clinically relevant PCa. PSA doubling time and PSA velocity may be more reliable to predict the risk of disease progression in patients with PCa. The first randomised controlled trial showed a comparable survival rate and risk of disease progression for external-beam radiation therapy and radical prostatectomy in patients with clinically localised PCa. In patients with advanced PCa, intermittent hormone therapy does not increase the risk of disease progression compared to continuous hormone therapy, while it has less impact on patient's quality of life. Patients receiving hormone therapy may benefit from an annual single-dose injection of zoledronic acid for the prevention of bone complications. Besides PSA, testosterone levels should be monitored in patients on androgen-deprivation treatment. Conclusions: Many interesting data in the field of PCa have been presented at this year's uro-oncologic meetings, which will improve the management of patients with PCa. © 2007 European Association of Urology., SCOPUS: re.j, info:eu-repo/semantics/published

Objectives: This report summarises major new findings in the field of prostate cancer (PCa) presented during the 2006 annual meetings of the European Association of Urology (EAU), American Urological Association (AUA), American Society of Clinical Oncology (ASCO), and the American Society for Therapeutic Radiology and Oncology (ASTRO). Methods: Urologic experts in the field of PCa selected relevant new findings that were discussed during a closed meeting in September 2006. The key points are communicated in this paper. Results: There was much discussion about the relevance of Prostate-Specific Antigen (PSA) screening. There seems to be no specific threshold for early detection of clinically relevant PCa. PSA doubling time and PSA velocity may be more reliable to predict the risk of disease progression in patients with PCa. The first randomised controlled trial showed a comparable survival rate and risk of disease progression for external-beam radiation therapy and radical prostatectomy in patients with clinically localised PCa. In patients with advanced PCa, intermittent hormone therapy does not increase the risk of disease progression compared to continuous hormone therapy, while it has less impact on patient's quality of life. Patients receiving hormone therapy may benefit from an annual single-dose injection of zoledronic acid for the prevention of bone complications. Besides PSA, testosterone levels should be monitored in patients on androgen-deprivation treatment. Conclusions: Many interesting data in the field of PCa have been presented at this year's uro-oncologic meetings, which will improve the management of patients with PCa. © 2007 European Association of Urology., SCOPUS: re.j, info:eu-repo/semantics/published

Background: More patients are being diagnosedwith prostate cancer at an earlier age with earlier stage disease because of advances in screening and detection. Investigators continue to explore the use of hormone therapy, particularly luteinizing hormone-releasing hormone (LHRH) analogues, earlier in the course of disease. Objective: This review summarizes clinical evidenceregarding the safety and efficacy of LHRH analogues in the treatment of locoregional disease or following biochemical failure. Methods: Relevant information from clinical studies was identified through a MEDLINE search of the medical literature published in English in the last 5 years (search terms: LHRH and prostate cancer). The search included prospective and retrospective clinical studies on LHRH therapy in locally advanced prostate cancer. Additional relevant publications published before 1999 were identified from citations in the resulting articles. Results: The available clinical evidence suggests that the use of LHRH analogues as adjuvant or neoadjuvant therapy in conjunction with radiation therapy may improve survival outcomes. Few studies have evaluated the use of LHRH analogues after biochemical failure. However, several related studies indicate that initiating hormone therapy earlier rather than later may provide some clinical benefit. When considering early initiation of LHRH therapy, the potential risks of long-term treatment must be considered. Physiologic changes, such as deterioration of body composition and bone quality, may have important effects on the risk of developing cardiovascular disease and osteoporosis. Conclusions: Although some clinical evidence supportsthe use of LHRH analogues as adjuvant or neoadjuvant therapy or following biochemical failure, further study is needed. In the meantime, clinicians should carefully weigh the potential benefits and risks of early hormone therapy when making treatment decisions. Copyright © 2005 Excerpta Medica, Inc., SCOPUS: re.j, info:eu-repo/semantics/published