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Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients.

ABSTRACT: Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression in chemo-naïve tissues were assessed in 121 muscle-invasive bladder cancer patients who underwent postoperative platinum-based chemotherapy. SDC1 concentrations were evaluated by ELISA in 52 baseline and 90 follow-up serum samples and tissue expressions were analyzed by immunohistochemistry in an independent cohort of 69 formalin-fixed paraffin-embedded tumor samples. Pre-treatment SDC1 serum levels were significantly higher in lymph node metastatic (p = 0.009) and female patients (p = 0.026). SDC1 tissue expression did not correlate with clinicopathological parameters. High pre-treatment SDC1 serum level and the presence of distant metastasis were independent risk factors for overall survival (Hazard ratio (HR): 1.439, 95% Confidence interval (CI): 1.003-2.065, p = 0.048; HR: 2.269, 95%CI: 1.053-4.887, p = 0.036). Our results demonstrate an independent association between high baseline serum SDC1 concentration and poor survival in platinum-treated patients. Analyzing baseline serum SDC1 levels may help to predict platinum-containing chemotherapy and could help to optimize therapeutic decision-making.

SUBMITTER: Olah C

PROVIDER: S-EPMC7690724 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients.

Olah Csilla C Tschirdewahn Stephan S Hoffmann Michèle J MJ Krafft Ulrich U Hadaschik Boris B Nyirady Peter P Szendröi Attila A Módos Orsolya O Csizmarik Anita A Kovalszky Ilona I Reis Henning H Szarvas Tibor T

Diagnostics (Basel, Switzerland) 20201023 11

Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression ...[more]

PMID: 33114033

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Project description:Importance:Neoadjuvant chemotherapy (NAC) followed by radical cystectomy improves survival compared with cystectomy alone for patients with bladder cancer. Although gemcitabine with cisplatin has become a standard NAC regimen, a dose-dense combination of methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) is being adopted at some institutions. Objective:To assess the association of neoadjuvant ddMVAC vs standard regimens with downstaging and overall survival among patients treated with radical cystectomy for bladder cancer. Design, Setting, and Participants:Cross-sectional analysis of data extracted from the medical records of a consecutive sample, after exclusions, of 1113 patients with bladder cancer of whom 824 had disease stage T2 or greater, who were treated with cystectomy at the Moffitt Cancer Center in Tampa, Florida, a tertiary care cancer center, between January 1, 2007, and May 31, 2017. Data were collected between November 14, 2016, and July 21, 2017, and analyzed between August 21, 2017, and December 8, 2017. Patients were compared based on type of NAC. Those who did not receive NAC were included as controls. Main Outcomes and Measures:Comparative rates and the association of any downstaging, complete response, and overall survival with ddMVAC and other NAC regimens and surgery alone. Outcomes were examined using Kaplan-Meier, adjusted logistic, Cox regression, and propensity-weighted models. Results:Of the 1113 patients who underwent cystectomy for bladder cancer, 861 (77.4%) were male, the median (interquartile range) age was 67 (60-74) years, 1051 (94.4%) were white, 27 (2.4%) black, 37 (3.3%) Hispanic/Latino, and 35 (3.1%) other race/ethnicity. Of 824 patients with muscle-invasive bladder cancer, 332 (40%) received NAC. Downstaging rates were 52.2% for ddMVAC, 41.3% for gemcitabine-cisplatin, and 27.0% for gemcitabine with carboplatin, and complete response (pT0N0) rates were 41.3% for ddMVAC, 24.5% for gemcitabine-cisplatin, and 9.4% for gemcitabine-carboplatin (2-sided P < .001). Adjusted analysis comparing ddMVAC with gemcitabine-cisplatin demonstrated a higher likelihood of downstaging (odds ratio [OR], 1.84; 95% CI, 1.10-3.09) and complete response (OR, 2.67; 95% CI, 1.50-4.77) with ddMVAC. Similar results were achieved with propensity score matching (OR, 1.52; 95% CI, 0.99-2.35). Patients who received ddMVAC had better overall survival than those treated with other chemotherapy regimens, although the observed survival benefit did not reach statistical significance in adjusted or propensity-matched models (hazard ratio, 0.44; 95% CI, 0.14-1.38; P = .16). Conclusions and Relevance:This study suggest that neoadjuvant ddMVAC followed by cystectomy is associated with a higher complete response (ypT0N0) rate than standard NAC. These data highlight and suggest the need to further investigate ddMVAC vs standard NAC in a prospective, randomized fashion.

Project description:Background:Baseline sarcopenia or severe lean muscle deficiency is independently associated with increased mortality after cystectomy for muscle-invasive urothelial carcinoma of the bladder (MIUC). The impact of chemotherapy on muscle mass in MIUC patients remains undefined. Objectives:To describe preoperative changes in body composition in MIUC patients receiving platinum-based neoadjuvant chemotherapy (NC). Methods:Patients with cT2-4 N0-1 M0 UC of the bladder who received NC were identified. Lumbar skeletal muscle index (SMI, cm2/m2), visceral adipose index (VAI, cm2/m2), and the subcutaneous and intramuscular adipose index (SAI, cm2/m2) were calculated using validated methodology (cross sectional area of skeletal muscle/height2 at L3) from measurement of soft tissue areas on pre- (pre-NC) and post-NC (post-NC) computed tomography. Patients were classified as sarcopenic according to consensus definitions: Male: SMI?<55 cm2/m2, Female: SMI?<38.5 cm2/m2. Pre-NC and post-NC median body mass index (BMI kg/m2), SMI, and adipose indices were compared. Results:The study cohort consisted of 26 patients, with a median age 70 years, including 7 females (27%). Chemotherapy regimens included dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (31%), gemcitabine/cisplatin (62%) and gemcitabine/carboplatin (3.8%) with a median of 3.5 (range 2-6) cycles. Median pre- and post-NC BMI were 27.1?kg/m2 and 27.2?kg/m2 (p?=?0.36). Median pre- and post-NC SMI were 49.1 cm2/m2 and 44.5 (p?<?0.001) respectively. Median percent change in SMI was -6.4% (range -30% to 10%). Pre-NC, 18 (69%) patients were sarcopenic vs. 21 (81%, p?=?0.002) post-NC. Median time between initiation of chemotherapy and cystectomy was 110 days. Conclusions:We observed a significant decrease in lean muscle mass among MIUC patients treated with platinum-based NC prior to cystectomy, with an associated increase in the prevalence of sarcopenia. Patients undergoing NC may benefit from pre-habilitative interventions to mitigate lean muscle loss prior to cystectomy.

Dataset Information

Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients.

Publications

Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients.

Similar Datasets

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