Effect of metabolic syndrome on pathologic features of prostate cancer

Kheterpal, Emil; Sammon, Jesse D.; Diaz, Mireya; Bhandari, Akshay; Trinh, Quoc Dien; Pokala, Naveen; Sharma, Pranav; Menon, Mani; Agarwal, Piyush K.

doi:10.1016/j.urolonc.2011.12.012

Cited by 43 publications

(28 citation statements)

References 22 publications

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“…Insulin resistance and hyperinsulinemia are associated with more aggressive disease and increased incidence of recurrence (Hammarsten & Hogstedt 2004, Kheterpal et al 2013. Consistent with these findings, time to CRPC is shorter in patients with metabolic syndrome compared with those without similar metabolic abnormalities (Flanagan et al 2011).…”

Section: :9mentioning

confidence: 62%

Uncontrolled diabetes predicts poor response to novel antiandrogens

Karantanos¹,

Karanika²,

Gignac³

2016

Endocrine-Related Cancer

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Metabolic abnormalities including hyperglycemia and hyperlipidemia have been associated with worse prognosis of prostate cancer (PCa), but there are limited data regarding their impact on the prognosis of castrate-resistant prostate cancer (CRPC) and the response of novel antiandrogens, namely abiraterone acetate (AA) and enzalutamide. Retrospective analysis of 61 patients with CRPC on AA or enzalutamide, treated at the Boston Medical Center, was performed. We evaluated hemoglobin A1c (HbA1c), HDL, LDL, Triglycerides and BMI within 2 months before the initiation of treatment with AA or enzalutamide and progression-free survival (PFS) under this treatment. Regression analysis and analysis of variance were used to evaluate the data. HbA1c levels were found to predict adversely the PFS on the novel agents (df (1, 37), P = 0.00, R 2 = 0.40, coeff = −3.28). The Kaplan-Meier analysis showed that there is significant difference in survival between the HbA1c 4.7-5.9% compared with patients with HbA1c 7.8-11.6% (6.72 ± 1.3 months, log rank test P < 0.0001) LDL (P = 0.07), HDL (P = 0.14), and triglycerides (P = 0.33) were not found to predict PFS. BMI predicted PFS positively (df (1.59), P = 0.02, R 2 = 0.09, coeff = 0.03), but not independently of HbA1c (P = 0.07). No significant implications of social and family history, previous chemotherapy regimen, and Gleason score with PFS were found. Multiple markers of patients' health state were not associated with HbA1c values. Uncontrolled diabetes can predict for poor response of CRPC patients to AA and enzalutamide determining PFS under this treatment. Elevated BMI can positively affect PFS at this stage of disease.

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Section: :9mentioning

confidence: 62%

Uncontrolled diabetes predicts poor response to novel antiandrogens

Karantanos¹,

Karanika²,

Gignac³

2016

Endocrine-Related Cancer

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“…27 Patients with higher BMI have been shown to have lower serum PSA compared to men with normal weight 28 which is also supported by our analysis. Hemodilution may cause PSA levels to meet threshold for biopsy later than their normal weight counterparts and may promote the diagnosis of higher risk disease at presentation 29 , as well as a decreased incidence of prostate cancer diagnosis. 4 In our cohort, however, there was no statistical difference in clinical T-stage or Gleason score between the men in various BMI groups, suggesting that hemodilution may not significantly impact results for this cohort.…”

Section: Discussionmentioning

confidence: 99%

Impact of obesity on outcomes after definitive dose‐escalated intensity‐modulated radiotherapy for localized prostate cancer

Wang

Murphy

Ruth

et al. 2015

Cancer

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INTRODUCTION Previous publications have shown conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy prior to the dose escalation era. Our goal is to determine whether increasing BMI is associated with CaP outcomes in men with localized CaP treated with dose escalated radiotherapy. METHODS We identified patients with localized (T1b-T4N0M0) CaP treated with definitive intensity modulated radiation therapy (IMRT) and image guidance (IGRT) from 2001–2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI category and the risk of biochemical failure (BF), distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). RESULTS Of the 1,442 patients identified, there were 20% with BMI<25 kg/m2, 48% with BMI 25–29.9 kg/m2, 23% with BMI 30–34.9 kg/m2, 6% with 35–39.9 kg/m2, and 4% with BMI≥40 kg/m2. Median follow-up was 47.6 months (range 1–145) with median age of 68 years (range 36–89). Median dose was 78Gy (range 76–80) and 30% of patients received androgen deprivation therapy. Increasing BMI was inversely associated with age (p<0.001) and pre-treatment PSA (p=0.018). On multivariable analysis, increasing BMI was associated with increased risk of BF (HR=1.03[95% CI 1.00–1.07], p=0.042), DM (HR=1.07[1.02–1.11], p=0.004), CSM (HR=1.15[1.07–1.23], p<0.001), and OM (HR=1.05[1.02–1.08], p=0.004). CONCLUSION For CaP patients receiving dose-escalated IMRT with IGRT, increasing BMI appears to be associated with an increased risk of biochemical failure, distant metastases development, cause-specific and overall survival.

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“…In addition we demonstrated the known association between shorter time to sAST and treatment with RT only or in patients who present with unfavorable risk PC. The clinical significance of our findings is that by taking measures prior to diagnosis of PC to reduce BMI—a modifiable risk factor—that more advanced disease at presentation and higher biochemical recurrence rates following initial treatment that are associated with a high BMI [10–12] may be reduced or avoided [27]. Therefore, this study raises the testable hypothesis that modifying one's health prior to a diagnosis of PC through interventions that lower BMI could lead to less aggressive disease at presentation, lower recurrence rates, decreased need for sAST, and therefore an overall better prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…The prevalence of obesity in USA population is increasing and is linked with increased overall mortality [2, 3]. Higher body mass index (BMI) has been shown in multiple studies of men with PC being associated with increased PC-specific mortality [4, 5], increased risk of PSA failure following radical prostatectomy [6, 7] or external beam radiation therapy (RT) [8, 9], higher risk disease at presentation [10–12], and higher likelihood of castrate-resistant disease or metastases following androgen suppression therapy (AST) [13], after adjusting for known risk factors.…”

Section: Introductionmentioning

confidence: 99%

Evidence Suggesting That Obesity Prevention Measures May Improve Prostate Cancer Outcomes Using Data from a Prospective Randomized Trial

et al. 2014

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Purpose. Increasing body mass index (BMI) is associated with higher risk prostate cancer (PC) at presentation. Whether increasing BMI also prompts earlier salvage androgen suppression therapy (sAST) is unknown. Materials and Methods. Between 1995 and 2001, 206 men with unfavorable risk PC were treated with radiation therapy (RT) or RT and six months of androgen suppression therapy in a randomized controlled trial (RCT). 108 sustained PSA failure; 51 received sAST for PSA approaching 10 ng/mL; 49 with BMI data comprised the study cohort. A multivariable Cox regression analysis identified pretreatment factors associated with earlier sAST receipt. Results. Increasing BMI prompted earlier sAST (median years: 3.7 for overweight/obese, 6.9 for normal weight; adjusted hazard ratio (AHR): 1.11; 95% CI: 1.04, 1.18; P = 0.002) as did high versus other risk PC (median: 3.2 versus 5.2 years; AHR: 2.01; 95% CI: 1.05, 3.83; P = 0.03). Increasing median time to sAST was observed for overweight/obese men with high versus other risk PC and for normal-weight men with any risk PC being 2.3, 4.6, and 6.9 years, respectively (P < 0.001 for trend). Conclusion. Increasing BMI was associated with earlier sAST. A RCT evaluating whether BMI reduction delays or eliminates need for sAST is warranted.

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Effect of metabolic syndrome on pathologic features of prostate cancer

Cited by 43 publications

References 22 publications

Uncontrolled diabetes predicts poor response to novel antiandrogens

Uncontrolled diabetes predicts poor response to novel antiandrogens

Impact of obesity on outcomes after definitive dose‐escalated intensity‐modulated radiotherapy for localized prostate cancer

Evidence Suggesting That Obesity Prevention Measures May Improve Prostate Cancer Outcomes Using Data from a Prospective Randomized Trial

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