| 1. |
- D'Andrea, David, et al.
(author)
-
Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guerin immunotherapy for T1G3/HG bladder cancer
- 2021
-
In: World journal of urology. - : Springer Nature. - 0724-4983 .- 1433-8726. ; 39:9, s. 3337-3344
-
Journal article (peer-reviewed)abstract
- Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guerin (BCG) for T1G3/HG urinary bladder cancer (UBC).Materials and methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression.Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55).Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
|
|
| 2. |
- Gontero, Paolo, et al.
(author)
-
Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin : Results of a Retrospective Multicenter Study of 2451 Patients
- 2015
-
In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:1, s. 74-82
-
Journal article (peer-reviewed)abstract
- 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.
|
|
| 3. |
- Gontero, Paolo, et al.
(author)
-
The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin
- 2016
-
In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 118:1, s. 44-52
-
Journal article (peer-reviewed)abstract
- 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.
|
|
| 4. |
- Lifshitz, Karin, et al.
(author)
-
Cardiovascular Proteomics : A Post Hoc Analysis from a Phase II Randomized Clinical Trial Comparing GnRH Antagonist vs GnRH Agonist among Men with Advanced Prostate Cancer
- 2021
-
In: The Journal of urology. - 1527-3792. ; 206:4, s. 952-959
-
Journal article (peer-reviewed)abstract
- PURPOSE: Recent studies demonstrated reduced cardiovascular (CV) risk with gonadotropin-releasing hormone (GnRH) antagonist, yet the underlying mechanism remains undetermined. The objective of this study was to examine longitudinal changes over time in established CV related proteins among men treated with GnRH agonists vs GnRH antagonist. MATERIALS AND METHODS: We performed a proteomics analysis of serum samples collected during a phase II randomized study among 80 men with advanced prostate cancer and preexisting CV disease who were randomized to receive a GnRH agonist (39) or GnRH antagonist (41) for 1 year. Serum samples were collected at baseline and at 3, 6 and 12 months following treatment, and analyzed levels of 188 proteins using the CV panel II and III of the Olink Multiplex platform (Olink Proteomics AB, Uppsala, Sweden). We fitted a linear mixed effects model to assess evidence of a treatment effect across CV related protein values. This included terms for treatment arm, protein levels and time-by-treatment interaction. Results were corrected for multiple testing using the Benjamini-Hochberg method. RESULTS: The CV proteomics analysis included 283 samples from 78 subjects. We identified 5 proteins with distinct patterns over time depending on study arm: human chitotriosidase, macrophage receptor with collagenous structure, cathepsin D, superoxide dismutase 2 and hydroxyacid oxidase 1. All 5 are associated with plaque stability and demonstrated an increased level among subjects in the GnRH antagonist arm compared to agonist. CONCLUSIONS: We compared longitudinal changes in CV proteins among men using androgen deprivation therapy. Our results support a direct protective effect of GnRH antagonist on plaque stability rather than a hazardous consequence of GnRH agonists on plaque rupture. This is a hypothesis generating study, and requires further confirmation.
|
|
| 5. |
- Witjes, J Alfred, et al.
(author)
-
The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer
- 2016
-
In: Urologic Oncology. - : Elsevier BV. - 1078-1439 .- 1873-2496. ; 34:11
-
Journal article (peer-reviewed)abstract
- 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, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given.
|
|
