Impact of obesity on outcomes after definitive dose escalated intensity modulated radiation therapy for localized prostate cancer.

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI<25 kg/m 2 ), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI >40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p<0.0001) and iPSA (p=0.047). There were 128 BF, 51 DM, 15 CSM, and 119 OM. Risk of BF, CSM, and OM were increased for obese class II and III compared to normal (all p<0.05). On multivariable analysis, for BF, HR was 2.1(p=0.057) for obese class II and 2.5 (p=0.043) for class III. For CSM, HR was 5.1 (p=0 .028) for class II and 5.15 (p=0.014) for class III. For OM, HR was 2.3 (p=0.022) for class II and 2.6(p=0.023) for class III. There was a trend toward increased DM for class III (p=0.057). Conclusions: For CaP patients receiving IMRT, those with higher levels of obesity may be at increased risk of BF and prostate cancer mortality, and should be considered for more aggressive treatment

The need for androgen deprivation therapy in patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiation therapy.

INTRODUCTION: To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era. MATERIALS AND METHODS: This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (\u3e= 23 months), or those with follow up \u3c 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates. RESULTS: Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS \u3e= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates. CONCLUSION: Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT

Effects of interruptions of external beam radiation therapy on outcomes in patients with prostate cancer.

INTRODUCTION: To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa). METHODS: We included men with localized PCa treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) of escalated dose (≥74 Gy in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI-designated cancer centre. Men receiving androgen deprivation therapy were excluded. The non-treatment day ratio (NTDR) was defined as the number of non-treatment days divided by the total elapsed days of therapy. NTDR was analysed for each National Comprehensive Cancer Network (NCCN) risk group. RESULTS: There were 1728 men included (839 low-risk, 776 intermediate-risk and 113 high-risk), with a median follow up of 53.5 months (range 12-185.8). The median NTDR was 31% (range 23-71%), translating to approximately 2 breaks (each break represents a missed treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The 75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was used as the cutoff for analysis. There were no significant differences in freedom from biochemical failure, freedom from distant metastasis, cancer specific survival, or overall survival for men with NTDR ≥33% compared to NTDR CONCLUSION: Unintentional treatment breaks during dose escalated external beam radiation therapy for PCa did not cause a significant difference in outcomes, although duration of follow up limits the strength of this conclusion

Comparison of prostate cancer diagnosis in patients receiving unrelated urological and non‐urological cancer care

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98801/1/bju12220.pd