Differences in Gene Expression in Muscle&amp;ndash; Invasive Bladder Cancer: A Comparison of Italian and American Patients

Williams, Shanna; Gandour‐Edwards, Regina; Deitch, Arline D.; Toscano, Salvador N.; Fan, Juanjuan; Sternberg, Cora N.; Pansadoro, Vito; Calabrò, Fabio; Rossetti, A.; White, Ralph W. deVere

doi:10.1159/000052481

Cited by 9 publications

(3 citation statements)

References 19 publications

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“…Whether the current results reflect more favorable biology is not clear, because this was not evaluated systematically in all patients. In a cohort of our patients that was characterized in a previous report conducted in collaboration with investigators at the University of California‐Davis in Sacramento, California 29. the majority of Italian patients had positive p53 status and p21 status and had negative bcl ‐2 status.…”

Section: Discussionmentioning

confidence: 97%

Can patient selection for bladder preservation be based on response to chemotherapy?

Sternberg

Pansadoro

Calabrò

et al. 2003

Cancer

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148

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BACKGROUNDNeoadjuvant chemotherapy for patients with muscle‐invasive bladder carcinoma is given to treat micrometastases and to preserve the bladder. The objective of this study was to evaluate the possibility of bladder preservation in patients with muscle‐invasive bladder carcinoma who were treated with neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M‐VAC) chemotherapy.METHODSOne hundred four consecutive patients with T2–T4,N0,M0 transitional cell carcinoma of the bladder were treated with 3 cycles of neoadjuvant M‐VAC chemotherapy. After clinical restaging, 52 patients underwent transurethral resection of the bladder (TURB) alone, 13 patients underwent partial cystectomy, and 39 patients underwent radical cystectomy.RESULTSThe median survival for the entire group was 7.49 years (95% confidence interval, 4.86–10.0 years). Forty‐nine patients (49%) were T0 at the time of TURB after receiving M‐VAC. Thirty‐one of 52 patients (60%) who received chemotherapy and underwent TURB alone were alive at a median follow‐up of 56 + months (range, 10–160 + months): Twenty‐three patients (44%) in that TURB group maintained an intact bladder. Of 13 responding patients with monofocal lesions who underwent partial cystectomy, only 1 patient required salvage cystectomy, and survival generally was good. The 5‐year survival rate for this group was 69%. With a long median follow‐up of 88 + months (range, 16–158 months), 4 patients (31%) were alive with a functioning bladder. In the radical cystectomy group, the median follow‐up was 45 months (range, 4–172 + months), and 15 of 39 patients (38%) patients remained alive. In 77 patients who had their tumors down‐staged to T0 or superficial disease, the median follow‐up was 63 months (range, 4–172 + months), and the 5‐year rate survival was 69%. This is in contrast to a 5‐year survival rate of only 26% in 27 patients who failed to respond and had a status ≥ T2 after receiving chemotherapy (median follow‐up, 31 months; range, 7–156 + months). The median survival for 27 elderly patients (age ≥ 70 years; median age, 73 years; range, 70–82 years) was 90 months (7.5 years). For elderly patients who underwent TURB and partial cystectomy, the 5‐year survival rate was 67% with a 109‐month (9‐year) median survival; 47% of patients preserved their bladders intact. The median follow‐up of the living elderly patients was 61 months (range, 20–120 + months).CONCLUSIONSBladder sparing in selected patients on the basis of response to neoadjuvant chemotherapy is a feasible approach that should be confirmed in prospective, randomized trials. Selected elderly patients are candidates for this approach. Cancer 2003;97:1644–52. © 2003 American Cancer Society.DOI 10.1002/cncr.11232

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Section: Discussionmentioning

confidence: 97%

Can patient selection for bladder preservation be based on response to chemotherapy?

Sternberg

Pansadoro

Calabrò

et al. 2003

Cancer

Self Cite

148

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“…Italian patients with p53+/p21+ tumors had significantly lower recurrence rates after TURB and chemotherapy than those having p53+/p21-tumors. The absence of p21 immunopositivity in the tumors of Italian patients may identify alterations in the p53 pathway that predict poor outcome [71]. • Advances in the understanding of the molecular biology of urothelial cancer continue to contribute to the identification of biochemical pathways on which new therapeutic approaches can be targeted.…”

Section: Emerging Therapiesmentioning

confidence: 99%

Localized and locally advanced bladder cancer

Calabrò

Sternberg

2002

Curr. Treat. Options in Oncol.

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Localized and locally advanced bladder cancer represents a heterogeneous spectrum of diseases with different biologic and clinical behavior. It varies with respect to invasive potential, propensity for metastases, and sensitivity to chemotherapy. Although several significant surgical advances have been made over the past 20 years in the treatment of muscle-invasive bladder cancer, resulting in decreases in perioperative morbidity and mortality and improvement of quality of life in patients with continent urinary diversions, the natural history of the disease has remained unaltered. Advances in chemotherapy for metastatic disease have prompted trials of systemic therapy in patients with early stage, high-risk disease administered before or after local therapy consisting of cystectomy or radiotherapy. The data available from nonrandomized and randomized trials have not definitively established the exact role of neoadjuvant chemotherapy and its impact on survival. Even if neoadjuvant chemotherapy does not improve survival, preliminary data suggest that bladder preservation may be possible in selected patients and that such combined therapy will hopefully lead to better patient management. The trials of postoperative chemotherapy provide insufficient evidence to support the routine use of adjuvant chemotherapy in clinical practice as a result of small sample size, confusing analyses, and the reporting of questionable conclusions. New large-scale, multicenter trials are imperative to provide convincing results. A better understanding of the microbiology of bladder cancer will influence the search for new therapeutic modalities. Molecular-targeted small-molecule therapy and monoclonal antibodies have begun to dominate contemporary studies.

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“…Other groups, including ours, have investigated whether Tp53 status can predict patient response. Unfortunately, the data generated by these studies remain controversial due to methodological challenges associated with determining Tp53 status, and Tp53 status is not currently used to inform treatment decisions [ 5 – 9 ]. Plimack et al recently reported defects in DNA repair genes is associated with response but this finding has not yet been prospectively validated [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy

et al. 2016

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The identification and development of biomarkers which predict response of muscle invasive bladder cancer (MIBC) patients to neoadjuvant chemotherapy would likely increase usage of this treatment option and thereby improve patient survival rates. MiRNA array and qRT-PCR validation was used to identify miRNA which are associated with response to neoadjuvant chemotherapy. RNA was extracted from a total of 41 archival, fully annotated, MIBC patient diagnostic biopsies (20 chemo-responders and 21 non-responders (response is defined as > 5 year survival rate and being pT0 post-chemotherapy)). Microarray and qPCR identified let-7c as being differentially expressed in chemo-responder versus non-responder patients. Patients with higher let-7c expression levels had significantly higher odds of responding to chemotherapy (p = 0.023, OR 2.493, 95% CI 1.121, 5.546), and assessment of let-7c levels allowed for prediction of patient response (AUC 0.72, positive predictive value 59%). Decreased let-7c was associated with MIBC incidence (p < 0.001), and significantly correlated with other related miRNA including those that were not differentially expressed between responders and non-responders. The combined data indicate let-7c plays a role in mediating chemoresistance to neoadjuvant chemotherapy in MIBC patients, and is a modest, yet clinically meaningful, predictor of patient response.

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Differences in Gene Expression in Muscle– Invasive Bladder Cancer: A Comparison of Italian and American Patients

Cited by 9 publications

References 19 publications

Can patient selection for bladder preservation be based on response to chemotherapy?

Can patient selection for bladder preservation be based on response to chemotherapy?

Localized and locally advanced bladder cancer

Decreased expression of let-7c is associated with non-response of muscle-invasive bladder cancer patients to neoadjuvant chemotherapy

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