Do molecular biomarkers have prognostic value in primary T1G3 bladder cancer treated with bacillus Calmette-Guerin intravesical therapy?

Park, Jinsung; Song, Cheryn; Shin, Eunah; Hong, Jun Hyuk; Kim, Choung‐Soo; Ahn, Hanjong

doi:10.1016/j.urolonc.2011.06.004

Cited by 42 publications

(36 citation statements)

References 48 publications

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“…The PTEN status findings in bladder cancer are in line with the previous studies. 3,17,19,[25][26][27] Taken together, our results indicate that deregulation of the PIK3CA/PTEN axis plays an important role in a subset of patients with locally advanced or Of the steroid receptors expression, the highest positivity rate was observed for AR, which has been correlated to better response to antiandrogen therapy in prostate, breast, and salivary gland cancers. [28][29][30] AR expression appears to progressively decrease with the tumor stage, 31 but we found AR expression in 16% of locally advanced/metastatic UC of the bladder, suggesting a significant potential for tailored therapy with antiandrogens in this specific subgroup.…”

Section: Discussionsupporting

confidence: 59%

Molecular Profiling of Infiltrating Urothelial Carcinoma of Bladder and Nonbladder Origin

Millis

Bryant

Basu

et al. 2015

Clinical Genitourinary Cancer

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Comprehensive molecular profiling of UC identified a large number of biomarkers aberrations that might direct treatment in conventional chemotherapies and targeted therapies, not currently recommended in this population. As a group, bladder UC exhibited higher levels of actionable biomarkers, suggesting that UC from different primary sites and non-UC are driven by different molecular pathways. These differences could have clinical implications resulting in different treatment regimens depending on the site of origin of UC.

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Section: Discussionsupporting

confidence: 59%

Molecular Profiling of Infiltrating Urothelial Carcinoma of Bladder and Nonbladder Origin

Millis

Bryant

Basu

et al. 2015

Clinical Genitourinary Cancer

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“…Park et al [26] and Esuvaranathan et al [30] evaluate pRB in patients subjected only to induction schedule with BCG (iBCG) and did not find any relationship with protein-positive staining and recurrence, RFS or PFS. These findings suggest that this marker could be a possible indicator of BCG response in patients treated with mBCG although more studies need to be performed in order to clarify this association.…”

Section: Resultsmentioning

confidence: 99%

Predictive Biomarkers of Bacillus Calmette-Guérin Immunotherapy Response in Bladder Cancer: Where Are We Now?

Lima

Dinis-Ribeiro

Longatto‐Filho

et al. 2012

Advances in Urology

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The most effective therapeutic option for managing nonmuscle invasive bladder cancer (NMIBC), over the last 30 years, consists of intravesical instillations with the attenuated strain Bacillus Calmette-Guérin (the BCG vaccine). This has been performed as an adjuvant therapeutic to transurethral resection of bladder tumour (TURBT) and mostly directed towards patients with high-grade tumours, T1 tumours, and in situ carcinomas. However, from 20% to 40% of the patients do not respond and frequently present tumour progression. Since BCG effectiveness is unpredictable, it is important to find consistent biomarkers that can aid either in the prediction of the outcome and/or side effects development. Accordingly, we conducted a systematic critical review to identify the most preeminent predictive molecular markers associated with BCG response. To the best of our knowledge, this is the first review exclusively focusing on predictive biomarkers for BCG treatment outcome. Using a specific query, 1324 abstracts were gathered, then inclusion/exclusion criteria were applied, and finally 87 manuscripts were included. Several molecules, including CD68 and genetic polymorphisms, have been identified as promising surrogate biomarkers. Combinatory analysis of the candidate predictive markers is a crucial step to create a predictive profile of treatment response.

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“…In a total of 51 patients consisting of pT1G3 tumours, expression of p53 alongside other cell cycle regulators such as cyclin D1 and cyclin D3 showed prognostic significance for PFS in multivariate analysis [26]. By contrast, Park et al were unable to find any prognostic value for seven markers including p53 and ki67 in 61 patients with pT1G3 UBC [27]. …”

Section: Discussionmentioning

confidence: 99%

Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

et al. 2012

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BackgroundTreatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC.MethodAQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guérin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test.Results59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 – 44.68; p=0.025).ConclusionsLoss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.

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Do molecular biomarkers have prognostic value in primary T1G3 bladder cancer treated with bacillus Calmette-Guerin intravesical therapy?

Cited by 42 publications

References 48 publications

Molecular Profiling of Infiltrating Urothelial Carcinoma of Bladder and Nonbladder Origin

Molecular Profiling of Infiltrating Urothelial Carcinoma of Bladder and Nonbladder Origin

Predictive Biomarkers of Bacillus Calmette-Guérin Immunotherapy Response in Bladder Cancer: Where Are We Now?

Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

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