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Item does not contain fulltext, 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-Guerin, 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.

Most bladder cancer (BC) patients need life-long, invasive and expensive monitoring and treatment, making it a serious burden on the health system. Thus, there is a pressing need for an accurate test to assist diagnosis and surveillance of BC as an alternative to cystoscopy. Mutations in human TERT, FGFR3, PIK3CA, and RAS genes have been proposed as potential molecular markers in bladder tumor. Their concomitant presence in urine samples has not been fully explored. We investigated a panel of mutations in DNA from exfoliated urinary cells of 255 BC patients at diagnosis. Forty-one mutations in TERT, FGFR3, PIK3CA, and RAS were analyzed by SNaPshot assay in relation to clinical outcome. In 81 of these patients under surveillance, the same set of mutations was screened in additional 324 samples prospectively collected. The most common mutations detected in urine at diagnosis were in the TERT promoter. In non-invasive BC, these mutations were related to high risk and grade (p < 0.0001) as well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05). Stronger associations were observed for combined TERT and FGFR3 mutations and number of recurrences (OR: 4.54 95% CI: 1.23-16.79, p=0.02). Analyses of the area under the curve for combinations of mutations detected at diagnosis and follow-up showed an accuracy of prediction of recurrence of 0.80 (95% CI: 0.71-0.89). Mutations in urine of BC patients may represent reliable biomarkers. In particular, TERT and FGFR3 mutations have a good accuracy of recurrence prediction.

Item does not contain fulltext, 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-Guerin, 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.

Contains fulltext : 153742.pdf (Publisher’s version ) (Closed access), 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.

Contains fulltext : 153742.pdf (Publisher’s version ) (Closed access), 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.

Contains fulltext : 153742.pdf (Publisher’s version ) (Closed access), 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.

1 maart 2010, Contains fulltext : 87719.pdf (publisher's version ) (Closed access), CONTEXT: Bacillus Calmette-Guerin (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

01 maart 2010, Contains fulltext : 87719.pdf (publisher's version ) (Closed access), CONTEXT: Bacillus Calmette-Guerin (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

01 maart 2010, Contains fulltext : 87719.pdf (publisher's version ) (Closed access), CONTEXT: Bacillus Calmette-Guerin (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