The Effectiveness of Off-Protocol Adjuvant Chemotherapy for Patients with Urothelial Carcinoma of the Urinary Bladder

Abstract Purpose: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting. Experimental Design: We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles. Results: The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (≥T3) and nodal involvement. Conclusion: Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy. Clin Cancer Res; 16(17); 4461–7. ©2010 AACR

The combination of serum insulin, osteopontin, and hepatocyte growth factor predicts time to castration-resistant progression in androgen dependent metastatic prostate cancer- an exploratory study

BackgroundWe hypothesized that pretreatment serum levels of insulin and other serum markers would predict Progression-free survival (PFS), defined as time to castration-resistant progression or death, in metastatic androgen-dependent prostate cancer (mADPC).MethodsSerum samples from treatment-naïve men participating in a randomized phase 3 trial of ADT +/- chemotherapy were retrospectively analyzed using multiplex assays for insulin and multiple other soluble factors. Cox proportional hazards regression models were used to identify associations between individual factor levels and PFS.ResultsSixty six patients were evaluable (median age = 72 years; median prostate surface antigen [PSA] = 31.5 ng/mL; Caucasian = 86 %; Gleason score ≥8 = 77 %). In the univariable analysis, higher insulin (HR = 0.81 [0.67, 0.98] p = 0.03) and C-peptide (HR = 0.62 [0.39, 1.00]; p = 0.05) levels were associated with a longer PFS, while higher Hepatocyte Growth Factor (HGF; HR = 1.63 [1.06, 2.51] p = 0.03) and Osteopontin (OPN; HR = 1.56 [1.13, 2.15]; p = 0.01) levels were associated with a shorter PFS. In multivariable analysis, insulin below 2.1 (ln scale; HR = 2.55 [1.24, 5.23]; p = 0.011) and HGF above 8.9 (ln scale; HR = 2.67 [1.08, 3.70]; p = 0.027) levels were associated with longer PFS, while adjusted by OPN, C-peptide, trial therapy and metastatic volume. Four distinct risk groups were identified by counting the number of risk factors (RF) including low insulin, high HGF, high OPN levels, and low C-peptide levels (0, 1, 2, and 3). Median PFS was 9.8, 2.0, 1.6, and 0.7 years for each, respectively (p < 0.001).ConclusionPretreatment serum insulin, HGF, OPN, and C-peptide levels can predict PFS in men with mADPC treated with ADT. Risk groups based on these factors are superior predictors of PFS than each marker alone