scholarly journals Impact of immunohistochemistry-based molecular subtype on predicting chemotherapy response and survival in patients with T1 stage bladder cancer after bladder-preserving treatment

Author(s):  
Jiangli Lu ◽  
Yijun Zhang ◽  
Chenyan Wu ◽  
Chengbiao Chu ◽  
Zhuowei Liu ◽  
...  

Abstract Objective To explore the immunohistochemistry-based molecular subtypes of bladder cancer, and their impact on the prognosis and the chemotherapy response between gemcitabine plus cisplatin intra-arterial chemotherapy and epirubicin-inducted intravesical chemotherapy, in patients with T1 stage bladder cancer after bladder-preserving treatment. Methods One hundred and seventy-six patients with T1 stage bladder cancer were selected for this study. Thirty-three patients underwent radical cystectomy, 43 received gemcitabine plus cisplatin intra-arterial chemotherapy and 100 received intravesical chemotherapy. The markers labeled with luminal (GATA3, Uroplakin II, CK20) and basal (CK5/6, CK14, CD44) phenotypes were chosen as candidate markers. Results One hundred and seventy-six patients were divided into 76 patients as basal/squamous (BASQ), 45 as the luminal A and 55 as the luminal B. Compared with the luminal B and BASQ tumors, the luminal A tumors showed a trend for better recurrence-free survival (P = 0.105) and progression-free survival (P = 0.093). The combination of CK20 and GATA3 was practical to identify the molecular phenotypes with total 84.9% accuracy and significantly associated with recurrence-free survival (P = 0.025) and progression-free survival (P = 0.004). The patient with BASQ tumors who received intravesical chemotherapy showed a trend for worse progression-free survival than the patient who received gemcitabine plus cisplatin intra-arterial chemotherapy or radical cystectomy. Furthermore, the patients with BASQ tumors experienced a significant improvement in progression-free survival after gemcitabine plus cisplatin intra-arterial chemotherapy compared with the patients who received intravesical chemotherapy (P = 0.011). Conclusions The immunohistochemistry-based molecular subtypes could predict the patient’s prognosis and clinically different chemotherapeutic survival outcomes in patients with T1 stage bladder cancer after bladder-preserving treatment.

2020 ◽  
Vol 9 (10) ◽  
pp. 3306
Author(s):  
Wojciech Krajewski ◽  
Marco Moschini ◽  
Łukasz Nowak ◽  
Sławomir Poletajew ◽  
Andrzej Tukiendorf ◽  
...  

Background and Purpose: The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2–6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no studies comparing post-BCG reTURB with the classic pre-BCG approach. The aim of this study was to assess whether the performance of reTURB after BCG induction in T1HG bladder cancer is related to potential oncological benefits. Materials and Methods: Data from 645 patients with primary T1HG bladder cancer treated between 2001 and 2019 in 12 tertiary care centres were retrospectively reviewed. The study included patients who underwent reTURB before BCG induction (Pre-BCG group: 397 patients; 61.6%) and those who had reTURB performed after BCG induction (Post-BCG group: 248 patients, 38.4%). The decision to perform reTURB before or after BCG induction was according to the surgeon’s discretion, as well as a consideration of local proceedings and protocols. Due to variation in patients’ characteristics, both propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. Results: The five-year recurrence-free survival (RFS) was 64.7% and 69.1% for the Pre- and Post-BCG groups, respectively, and progression-free survival (PFS) was 82.7% and 83.3% for the Pre- and Post-BCG groups, respectively (both: p > 0.05). Similarly, neither RFS nor PFS differed significantly for a five-year period or in the whole time of observation after the PSM and IPW matching methods were used. Conclusions: Our results suggest that there might be no difference in recurrence-free survival and progression-free survival rates, regardless of whether patients have reTURB performed before or after BCG induction.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12528-e12528
Author(s):  
Marina Elena Cazzaniga ◽  
Paolo Pronzato ◽  
Francesco Schettini ◽  
Lucia Del Mastro ◽  
Maria Riemma ◽  
...  

e12528 Background: Pts with ABC have a diverse clinical course and OS rates vary significantly among pts. New strategies had potentially changed the natural history of these pts, however data from clinical studies are still lacking and Real-World Studies (RWS) are crucial in clinical outcome evaluation. Methods: AMBRA is a longitudinal cohort study, aiming to describe the choice of first and subsequent lines of treatment in HER2-ve ABC pts receiving at least one CHT (SABCS 2016, P5-15-07 & P5-14-09) in the years 2012-2015. The present analysis is focused on the description of Progression-Free Survival (PFS) and OS according to the biologic subtype in the deceased population. So far, 791/1500 pts have been registered into the study and 255 (32.2%) are evaluable. Time to event analysis between subtypes was evaluated by Cox-Mantel Hazard Ratio and Logrank Test. DFS by Wilcoxon Rank-Sum Test. Results: Pts distribution according to molecular subtype was: Luminal A (86, 33.7%), Luminal B (107 (42.1%), TNBC (62, 24.3%). Median ages at diagnosis were 55.8, 52.9 and 55.1 years for the 3 subgroups, respectively. Mean DFS was significantly different according to the molecular subtypes: 87.28, 61.37 and 23.9 months. The difference between Luminal B and TNBC is statistically significant as well. Mean PFS of first-line therapy was 17.9 11.7 and 7.8 months respectively. Mean OS from first progression was 32.9 24.2 and 15.8 months respectively. Statistical details. Conclusions: Our data confirm in a RWS the different biological behaviour between Lum A and B. Metastatic life span is quite good for Luminal and disappointing for TNBC. Median time from last CHT and Death is quite short and similar.[Table: see text]


JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1304 ◽  
Author(s):  
Nancy Y. Yu ◽  
Adina Iftimi ◽  
Christina Yau ◽  
Nicholas P. Tobin ◽  
Laura van ’t Veer ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Won Sik Ham ◽  
Jee Soo Park ◽  
Won Sik Jang ◽  
Young Deuk Choi ◽  
Jongchan Kim

AbstractThere is evidence that a history of benign prostatic hyperplasia increases the incidence of bladder cancer, and treatment with 5-alpha reductase inhibitor or androgen deprivation therapy reduces recurrence of non-muscle invasive bladder cancer. We aimed to evaluate whether prostate volume affects its prognosis. We reviewed medical records of men who underwent transurethral resection of bladder tumor due to non-muscle invasive bladder cancer from January 2012 to December 2017. Patients were divided into two groups based on prostate volume measured by computed tomography (group 1: 264 patients with ≤ 30 mL, group 2: 124 patients with > 30 mL). Propensity score matching analysis was used for adjust selection bias, and then assessed recurrence-free survival and progression-free survival. With a median follow up duration of 52 months, group 1 showed higher 5-year recurrence-free and progression-free survival (69.3% vs 47.0%, p = 0.001; 96.7% vs 87.7%, p = 0.002). Further, cox-regression analysis showed that tumor size (HR = 1.292 p < 0.001), multifocal tumor (HR = 1.993, p < 0.001), adjuvant intravesical therapy (chemotherapy: HR = 0.580, p = 0.037 and bacillus Calmette–Guérin: HR = 0.542, p = 0.004) and prostate volume (HR = 2.326, p < 0.001) were significant predictors of recurrence-free survival. Prostate volume (HR = 2.886, p = 0.014) was also associated with PFS with age (HR = 1.043, p = 0.044) and tumor grade (HR = 3.822, p = 0.013). We conclude higher prostate volume is associated with worse recurrence and progression-free survival in non-muscle invasive bladder cancer.


Diagnostics ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 573
Author(s):  
Michela Palleschi ◽  
Roberta Maltoni ◽  
Sara Ravaioli ◽  
Alessandro Vagheggini ◽  
Francesca Mannozzi ◽  
...  

CDK4/6 inhibitors (CDK4/6i) are recommended in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC). Up to now, no prognostic biomarkers have been identified in this setting. We retrospectively analyzed the expression of progesterone receptor (PR) and Ki67, assessed by immunohistochemistry, in 71 ABC patients treated with CDK4/6i and analyzed the impact of these markers on progression-free survival (PFS). The majority of patients 63/71 (88.7%) received palbociclib, 4 (5.6%) received ribociclib, and 4 (5.6%) received abemaciclib. A higher median value of Ki67 was observed in cases undergoing second-line treatment (p = 0.047), whereas the luminal B subtype was more prevalent (p = 0.005). In the univariate analysis of the first-line setting, luminal A subtype showed a trend towards a correlation with a longer PFS (p = 0.053). A higher continuous Ki67 value led to a significantly shorter PFS. When the interaction between pathological characteristics and line of treatment was considered, luminal B subtype showed a significantly (p = 0.043) worse outcome (Hazard Ratio (HR) 2.84; 1.03–7.82 95% Confidence Interval (CI)). PFS in patients undergoing endocrine therapy plus CDK4/6i was inversely correlated with Ki67 expression but not with PR, suggesting that tumor proliferation has a greater impact on cell cycle inhibitors combined with endocrine therapy than PR expression.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhongbao Zhou ◽  
Yuanshan Cui ◽  
Shuangfeng Huang ◽  
Zhipeng Chen ◽  
Yong Zhang

BackgroundDue to the poor prognosis, the treatment of high-risk bladder cancer (HRBC) remains controversial. This meta-analysis aims to access the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) versus IC alone after bladder-sparing surgery in HRBC.MethodsA systematic search of PubMed, Cochrane Library databases, EMBASE (until June 2020) was conducted. PRISMA checklist was followed. The data were analyzed by RevMan v5.3.0.ResultsA total of five articles including 843 patients were studied. The analysis demonstrated that the IAC + IC group had a greater improvement of overall survival (P = 0.02) and significant reduction in terms of tumor recurrence rate (P = 0.0006) and tumor progression rate (P = 0.008) compared with the IC group. The recurrence-free survival in the IAC + IC group was significantly higher than that in the IC group (P = 0.004), but there was no significant difference in progression-free survival between the two groups (P = 0.32). In addition, the combination of IAC and IC significantly extended tumor recurrence interval (P = 0.0001) and reduced tumor-specific death rate (P = 0.01) for patients with HRBC compared with IC alone. For side effects related with IAC, although about half of the patients experienced some toxicities, most of them were mild and reversible (grades 1–2, 22.3% vs. grade 3–4, 2.7%), mainly including nausea/vomiting (P = 0.0001), neutropenia (P = 0.002), and alanine aminotransferase (P = 0.0001).ConclusionPatients with HRBC treated with IAC + IC after bladder-sparing surgery had a marked improvement in the overall survival, recurrence-free survival, time interval to first recurrence, tumor recurrence rate, tumor progression rate, and tumor-specific death rate than patients treated with IC alone. However, progression-free survival was not significantly correlated with treatment strategy. In addition, patients seemed to tolerate well the toxicities related with IAC. Systematic Review RegistrationPROSPERO, identifier CRD42021232679.


2021 ◽  
Author(s):  
Won Sik Ham ◽  
Jee Soo Park ◽  
Won Sik Jang ◽  
Young Deuk Choi ◽  
Jongchan Kim

Abstract There is evidence that a history of benign prostatic hyperplasia increases the incidence of bladder cancer, and treatment with 5-alpha reductase inhibitor or androgen deprivation therapy reduces recurrence of non-muscle invasive bladder cancer. We aimed to evaluate whether prostate volume affects its prognosis. We reviewed medical records of men who underwent transurethral resection of bladder tumor due to non-muscle invasive bladder cancer from January 2012 to December 2017. Patients were divided into two groups based on prostate volume measured by computed tomography (group 1: 264 patients with ≤30 mL, group 2: 124 patients with >30 mL), and assessed recurrence-free survival and progression-free survival. With a median follow up duration of 52 months, group 1 showed higher 5-year recurrence-free and progression-free survival (69.3% vs 47.0%, p=0.001; 96.7% vs 87.7%, p=0.002). Further, cox-regression analysis showed that tumor size (HR=1.292 p<0.001), multifocal tumor (HR=1.993, p<0.001), adjuvant intravesical therapy (chemotherapy: HR=0.580, p=0.037 and bacillus Calmette-Guérin: HR=0.542, p=0.004) and prostate volume (HR=2.326, p<0.001) were significant predictors of recurrence-free survival. Prostate volume (HR=2.886, p=0.014) was also associated with PFS with age (HR=1.043, p=0.044) and tumor grade (HR=3.822, p=0.013). We conclude higher prostate volume is associated with worse recurrence and progression-free survival in non-muscle invasive bladder cancer.


2017 ◽  
Vol 11 ◽  
pp. 117822341774585
Author(s):  
Lakmini Mudduwa ◽  
Harshini Peiris ◽  
Shania Gunasekara ◽  
Deepthika Abeysiriwardhana ◽  
Thusharie Liyanage

Aim: To study the prognostic value of immunohistochemically detected low Claudin3 expression in breast cancers. Methods: This retrospective study included patients with breast cancer who were investigated at our unit from 2006 to 2015. Tissue microarrays were constructed, and immunohistochemical staining was done to assess the Claudin3 expression and to classify breast cancers according to the immunohistochemical surrogates for molecular classification. Kaplan-Meier model and log-rank test were used for recurrence-free survival and breast cancer–specific survival analysis. Results: Of the 853 patients, overall low expression of Claudin3 was seen in 18.4%. Recurrence-free survival of patients with overall low Claudin3 breast cancers was poor in luminal A ( P = .006) and luminal B (Her2−) ( P = .009) subtypes compared with those who had Claudin3 expression in each group. Conclusions: Assessment of Claudin3 expression by immunohistochemistry is suggested for luminal A and luminal B (Her2−) subtypes to identify patients with poor prognosis.


2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jing Yan ◽  
Bin Zhang ◽  
Shuaitong Zhang ◽  
Jingliang Cheng ◽  
Xianzhi Liu ◽  
...  

AbstractGliomas can be classified into five molecular groups based on the status of IDH mutation, 1p/19q codeletion, and TERT promoter mutation, whereas they need to be obtained by biopsy or surgery. Thus, we aimed to use MRI-based radiomics to noninvasively predict the molecular groups and assess their prognostic value. We retrospectively identified 357 patients with gliomas and extracted radiomic features from their preoperative MRI images. Single-layered radiomic signatures were generated using a single MR sequence using Bayesian-regularization neural networks. Image fusion models were built by combing the significant radiomic signatures. By separately predicting the molecular markers, the predictive molecular groups were obtained. Prognostic nomograms were developed based on the predictive molecular groups and clinicopathologic data to predict progression-free survival (PFS) and overall survival (OS). The results showed that the image fusion model incorporating radiomic signatures from contrast-enhanced T1-weighted imaging (cT1WI) and apparent diffusion coefficient (ADC) achieved an AUC of 0.884 and 0.669 for predicting IDH and TERT status, respectively. cT1WI-based radiomic signature alone yielded favorable performance in predicting 1p/19q status (AUC = 0.815). The predictive molecular groups were comparable to actual ones in predicting PFS (C-index: 0.709 vs. 0.722, P = 0.241) and OS (C-index: 0.703 vs. 0.751, P = 0.359). Subgroup analyses by grades showed similar findings. The prognostic nomograms based on grades and the predictive molecular groups yielded a C-index of 0.736 and 0.735 in predicting PFS and OS, respectively. Accordingly, MRI-based radiomics may be useful for noninvasively detecting molecular groups and predicting survival in gliomas regardless of grades.


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