Tumor Multiplicity Is an Independent Prognostic Factor of Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guerin Immunotherapy

Ajili, Faouzia; Manaï, Mohamed; Darouiche, Amine; Chébil, Mohamed; Boubaker, Samir

doi:10.3109/01913123.2012.681833

Cited by 12 publications

(5 citation statements)

References 26 publications

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“…We first observed that treatment outcome was influenced by age, treatment scheme and tumour multifocallity, as showed in other reports (Bohle and Bock, 2004; Joudi et al , 2006; Fernandez-Gomez et al , 2008; Malmstrom et al , 2009; Kohjimoto et al , 2010; Ajili et al , 2012). To overcome the samples heterogeneity, these variables were taken into account in multivariate analysis models to assess the influence of tumour-associated glycans in BCG response.…”

Section: Discussionsupporting

confidence: 59%

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

et al. 2013

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Background:High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T).Methods:In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn.Results:From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344–5.254); P=0.005), maintenance schedule (HR=0.480; (0.246–0.936); P=0.031) and multifocallity (HR=2.065; (1.033–4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148–0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death.Conclusion:s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.

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Section: Discussionsupporting

confidence: 59%

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

et al. 2013

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“…38 Although not specific to patients with IR disease, a more recent retrospective analysis examining the clinical and pathologic data of 112 patients with primary NMIBC treated with TURBT and BCG found tumor multiplicity to be the only independent predictor of disease recurrence. 39 …”

Section: Resultsmentioning

confidence: 99%

Defining and Treating the Spectrum of Intermediate Risk Nonmuscle Invasive Bladder Cancer

Kamat

Witjes

Brausi³

et al. 2014

Journal of Urology

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Introduction Low-, intermediate- and high-risk categories have been defined to help guide the treatment of patients with NMIBC (Ta, T1, CIS). However, while low- and high-risk disease have been well-classified, the intermediate-risk (IR) category has traditionally comprised a heterogeneous group of patients that do not fit into either of these categories. As a result, many urologists remain uncertain about the categorization of patients as ‘intermediate-risk’ as well as the selection of the most appropriate therapeutic option for this patient population. Purpose To examine current literature and clinical practice guidelines on IR NMIBC and, based on this review, provide urologists with a better understanding of this heterogeneous risk group as well as practical recommendations for the management of IR patients. Materials and Methods The IBCG analyzed published clinical trials, meta-analyses and current clinical practice guidelines that examined IR NMIBC available as of September 2013. The definition of IR, patient outcomes and guideline recommendations were considered, as were the limitations of the available literature and additional parameters that may be useful in guiding treatment decisions in IR patients. Results Currently, definitions and management recommendations for IR NMIBC vary. The most simple and practical definition is that proposed by the IBCG and the AUA: multiple and/or recurrent low-grade Ta tumors. The IBCG proposes that the following factors be considered to aid in clinical decisions in IR disease: number (>1) and size (> 3cm) of tumors, timing (recurrence within 1 year) and frequency (> 1 per year) of recurrences, and previous treatment. In patients without these risk factors, a single, immediate instillation of chemotherapy is advised. In those with 1–2 risk factors, adjuvant intravesical therapy (intravesical chemotherapy or maintenance BCG) is recommended, and previous intravesical therapy should be considered when choosing between these adjuvant therapies. For those with 3–4 risk factors, maintenance BCG is recommended. It is also important that all IR patients are accurately risk stratified both at initial diagnosis and during subsequent follow-up. This requires an appropriate TURBT, vigilance to rule out CIS or other potential high-risk tumors, and review of histological material directly with the pathologist. Conclusions IR disease is a heterogeneous group and there is paucity of independent studies comparing therapies and outcomes in the subgroups of IR patients. The IBCG has proposed a management algorithm to assist in this regard that considers tumor characteristics, timing and frequency of recurrences and previous treatment. Subgroup analyses of the IR subjects in pivotal EORTC trials and meta-analyses will be important to validate the proposed algorithm and support clear evidence-based recommendations for the subgroups of IR patients.

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“…The majority of studies (10 of 12) investigated the associations of smoking status with disease recurrence [11][12][13][14][15][16]17 19,20]. Attributable to variations in the study sample sizes, there were variations of the comparator groupings.…”

Section: Impact Of Smoking On Outcomesmentioning

confidence: 97%

“…To summarize the best available evidence, we selected 12 studies that met the inclusion criteria for this review article of which five studies were published prior to 2011. The associations of smoking with disease recurrence and progression, the two most important disease outcomes in NMIBC, are summarized in Table 1 [11][12][13][14][15][16][17][18][19][20][21][22]. Although there are minor variations in disease outcome definitions among studies, the definitions were sufficiently similar to allow for evidence synthesis.…”

Section: Impact Of Smoking On Outcomesmentioning

confidence: 98%

Smoking and smoking cessation effects on oncological outcomes in nonmuscle invasive bladder cancer

Simonis

Shariat

Rink

2014

Current Opinion in Urology

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Although there are limited data, the growing body of evidence indicates that smoking increases the risk of disease recurrence and potentially disease progression in patients with NMIBC. Current and heavy long-term smokers seem to be at the greatest risk for both end points. Smoking cessation may limit these effects thereby improving prognosis. To improve our understanding of the associations of this important, modifiable risk factor with outcomes in patients with NMIBC, smoking should be incorporated into clinical trial design and analysis. It is the duty of each urologist to raise awareness regarding the greatest preventable cause of the development of bladder cancer, morbidity, and mortality.

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Tumor Multiplicity Is an Independent Prognostic Factor of Non-muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guerin Immunotherapy

Abstract: Significant independent predictor for recurrence was multiplicity which offers important clinical information and may be a useful tool in the selection of suitable candidates for BCG-immunotherapy.

Cited by 12 publications

References 26 publications

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

Defining and Treating the Spectrum of Intermediate Risk Nonmuscle Invasive Bladder Cancer

Smoking and smoking cessation effects on oncological outcomes in nonmuscle invasive bladder cancer

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