Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer.

PURPOSE: The objective of this study was to determine whether limiting the doses delivered to the penile bulb (PB) and corporal bodies with intensity modulated radiation therapy (IMRT) preserves erectile function compared with standard IMRT in men with prostate cancer. METHODS AND MATERIALS: A total of 117 patients with low- to intermediate-risk, clinical T1a-T2c prostate adenocarcinoma were enrolled in a single-institution, prospective, single-blind, phase 3 randomized trial. All received definitive IMRT to 74 to 80 Gy in 37 to 40 fractions and standard IMRT (s-IMRT) or erectile tissue-sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the penile bulb and corporal bodies to ≤15 Gy and ≤7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function and phosphodiesterase type 5 inhibitor (PDE5) medication records. RESULTS: Sixty-two patients received ETS-IMRT, and 54 received s-IMRT; 1 patient did not receive radiation therapy. Before treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, P = .53). Of 85 evaluable patients with International Index of Erectile Function and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (P = .86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (P = .54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-year 91.8% vs 90.7%, respectively, P = .77), with a median follow-up of 7.4 years. There were no differences in acute or late gastrointestinal or genitourinary toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, although power was limited by attrition and unplanned dosimetric crossover. CONCLUSIONS: ETS-IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.

Patient-reported Quality of Life After SBRT, LDR, and HDR Brachytherapy for Prostate Cancer: A Comparison of Outcomes.

PURPOSE: We sought to compare changes in patient-reported quality of life (PRQOL) following stereotactic body radiation therapy (SBRT), high dose rate (HDR), and low dose rate (LDR) brachytherapy for prostate cancer. MATERIALS AND METHODS: International Prostate Symptom Score (IPSS), Sexual Health Inventory For Men (SHIM), and Expanded Prostate cancer Index Composite Short Form (EPIC-26) were prospectively collected for men with low/intermediate-risk cancer treated at a single institution. We used Generalized Estimating Equations to identify associations between variables and early (3 to 6 mo) or late (1 to 2 y) PRQOL scores. Minimally important differences (MID) were compared with assess clinical relevance. RESULTS: A total of 342 LDR, 159 HDR, and 112 SBRT patients treated from 2001 to 2018 were eligible. Gleason score, PSA, and age were lower among LDR patients compared with HDR/SBRT. Unadjusted baseline IPSS score was similar among all groups. Adjusted IPSS worsened at all time points compared with baseline after LDR/HDR. At early/late time points, rates of IPSS MID after LDR were higher compared to HDR/SBRT. There were no IPSS differences between SBRT and HDR. All modalities showed early and late SHIM worsening. There were no temporal differences in SHIM between SBRT and brachytherapy. There were no differences in EPIC subdomains between HDR and SBRT. Bowel symptoms worsened early after SBRT, whereas urinary irritative/obstructive symptoms worsened late after HDR. Among all domains, MID after SBRT and HDR were similar. CONCLUSIONS: In a cohort of patients treated with modern radiotherapy techniques, HDR and SBRT resulted in clinically meaningful improved urinary PRQOL compared with LDR.

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

PURPOSE: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use (P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

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<33% for each risk group. Multivariable analyses including NTDR, age, race, Gleason score, T stage, and PSA were performed using the proportional hazards regression procedure. NTDR≥33% was not significantly associated with increased hazard ratio for outcomes in each risk group compared to NTDR<33%. 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.

Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer.

BACKGROUND: The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. METHODS: The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. RESULTS: A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. CONCLUSIONS: In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society.

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 (>= 23 months), or those with follow up < 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 >= 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.

Prostate Cancer Patients With Unmanaged Diabetes or Receiving Insulin Experience Inferior Outcomes and Toxicities After Treatment With Radiation Therapy.

BACKGROUND: The purpose of the study was to determine the effect of type 2 diabetes mellitus (T2DM) on outcomes and toxicities among men with localized prostate cancer receiving definitive radiation therapy. PATIENTS AND METHODS: We performed a retrospective review of 3217 patients, from 1998 to 2013, subdivided into 5 subgroups: (I) no T2DM; (II) T2DM receiving oral antihyperglycemic agent that contains metformin, no insulin; (III) T2DM receiving nonmetformin oral agent alone, no insulin; (IV) T2DM receiving any insulin; and (V) T2DM not receiving medication. Outcome measures were overall survival, freedom from biochemical failure (BF), freedom from distant metastasis, cancer-specific survival, and toxicities. Kaplan-Meier analysis, log rank tests, Fine and Gray competing risk regression (to adjust for patient and lifestyle factors), Cox models, and subdistribution hazard ratios (sHRs) were used. RESULTS: Of the 3217 patients, 1295 (40%) were low-risk, 1192 (37%) were intermediate-risk, and 652 (20%) were high risk. The group I to V distribution was 81%, 8%, 5%, 3%, and 4%. The median dose was 78 Gy, and the median follow-up time was 50 (range, 1-190) months. Group V had increased mortality (sHR, 2.1; 95% confidence interval [CI], 0.66-1.54), BF (sHR, 2.14; 0.88-1.83), and cause-specific mortality (sHR, 3.87; 95% CI, 1.31-11). Acute toxicities were higher in group IV versus group I (genitourinary: 38% vs. 26%; P = .01; gastrointestinal: 21% vs. 5%; P = 001). Late toxicities were higher in groups IV and V versus group I (12%-14% vs. 2%-6%; P < .01). CONCLUSION: Men with T2DM not receiving medication and men with T2DM receiving insulin had worse outcomes and toxicities compared to other patients.

Patient reported outcomes among treatment modalities for prostate cancer.

INTRODUCTION: To characterize patient reported outcomes for urinary and sexual function using International Prostate Symptom Score (IPSS) and Sexual Health Inventory for Men (SHIM) comparing intensity modulated radiation therapy (IMRT), low dose rate brachytherapy (LDR), post-prostatectomy IMRT (PPRT), and radical prostatectomy (RP). MATERIALS AND METHODS: Patients treated for prostate cancer from 2001-2012 completed self-reported SHIM and IPSS surveys. Subgroups were created by baseline score. Mean change from baseline was determined at each time point for the cohort and subgroups. Statistical analysis was performed with generalized estimating equation method. Incontinence was not captured in the questionnaires. RESULTS: A total of 14,523 IPSS surveys from 3,515 men were evaluated. Patients treated with IMRT experienced a minimal decrease in IPSS score from baseline. PPRT scores did not differ from IMRT at any time point (range: +/- 3 points from baseline in IPSS score over 50 months). LDR had an initial IPSS rise (between 5-10 points on the IPSS over 1-9 months) versus IMRT but returned to comparable levels at 34 months. RP was associated with a lower IPSS versus IMRT. LDR had the largest rise from baseline, with return toward baseline. A total of 2,624 SHIM surveys from 857 men were evaluated. LDR and PPRT did not differ from IMRT at any time point (range: +/- 5 points from baseline in SHIM score for 36 months). RP experienced the largest decline from baseline (up to -7 points on SHIM score), at 3 to 7 months; RP had a larger early decrease in SHIM score versus IMRT between 3 and 22 months, after which there was no difference. CONCLUSIONS: IPSS and SHIM score patterns differed among treatment modalities. These data can be used to predict changes in urinary and sexual function over time based on modality and baseline score.

Men's health supplement use and outcomes in men receiving definitive intensity-modulated radiation therapy for localized prostate cancer.

BACKGROUND: Approximately 50% of newly diagnosed cancer patients start taking dietary supplements. Men's health supplements (MHSs), which we define as supplements that are specifically marketed with the terms men's health and prostate health (or similar permutations), are often mislabeled as having potential anticancer benefits. OBJECTIVE: We evaluated the effects of MHSs on patient outcomes and toxicities in patients who were undergoing definitive intensity-modulated radiation therapy (IMRT) for localized prostate cancer. DESIGN: This retrospective analysis included patients who were being treated at a National Cancer Institute-designated comprehensive cancer center and consented to have information stored in a prospective database. MHSs were queried online. Outcome measures were freedom from biochemical failure (FFBF) (biochemical failure was defined with the use of the prostate-specific antigen nadir + 2-ng/mL definition), freedom from distant metastasis (FFDM), cancer-specific survival (CSS), and overall survival (OS) as well as toxicities. Kaplan-Meier analysis, log-rank tests, Fine and Gray competing-risk regression (to adjust for patient and lifestyle factors), and Cox models were used. RESULTS: From 2001 to 2012, 2207 patients were treated with IMRT with a median dose of 78 Gy, and a median follow-up of 46 mo. Of these patients, 43% were low risk, 37% were intermediate risk, and 20% were high risk; 10% used MHSs. MHSs contained a median of 3 identifiable ingredients (range: 0-78 ingredients). Patients who were taking an MHS compared with those who were not had improved 5-y OS (97% compared with 92%, respectively; P = 0.01), but there were no differences in the FFBF (94% compared with 89%, respectively; P = 0.12), FFDM (96% compared with 97%, respectively; P = 0.32), or CSS (100% compared with 99%, respectively; P = 0.22). The unadjusted association between MHS use and improved OS was attenuated after adjustment for patient lifestyle factors and comorbidities. There was no difference in toxicities between the 2 groups (late-grade 3-4 genitourinary <3%; gastrointestinal <4%). CONCLUSION: The use of MHSs is not associated with outcomes or toxicities.

A comparison of robotic arm versus gantry linear accelerator stereotactic body radiation therapy for prostate cancer.

Prostate cancer is the most prevalent cancer diagnosed in men in the United States besides skin cancer. Stereotactic body radiation therapy (SBRT; 6-15 Gy per fraction, up to 45 minutes per fraction, delivered in five fractions or less, over the course of approximately 2 weeks) is emerging as a popular treatment option for prostate cancer. The American Society for Radiation Oncology now recognizes SBRT for select low- and intermediate-risk prostate cancer patients. SBRT grew from the notion that high doses of radiation typical of brachytherapy could be delivered noninvasively using modern external-beam radiation therapy planning and delivery methods. SBRT is most commonly delivered using either a traditional gantry-mounted linear accelerator or a robotic arm-mounted linear accelerator. In this systematic review article, we compare and contrast the current clinical evidence supporting a gantry vs robotic arm SBRT for prostate cancer. The data for SBRT show encouraging and comparable results in terms of freedom from biochemical failure (>90% for low and intermediate risk at 5-7 years) and acute and late toxicity (<6% grade 3-4 late toxicities). Other outcomes (eg, overall and cancer-specific mortality) cannot be compared, given the indolent course of low-risk prostate cancer. At this time, neither SBRT device is recommended over the other for all patients; however, gantry-based SBRT machines have the abilities of treating larger volumes with conventional fractionation, shorter treatment time per fraction (~15 minutes for gantry vs ~45 minutes for robotic arm), and the ability to achieve better plans among obese patients (since they are able to use energies >6 MV). Finally, SBRT (particularly on a gantry) may also be more cost-effective than conventionally fractionated external-beam radiation therapy. Randomized controlled trials of SBRT using both technologies are underway.

Comparison of outcomes and toxicities among radiation therapy treatment options for prostate cancer.

We review radiation therapy (RT) options available for prostate cancer, including external beam (EBRT; with conventional fractionation, hypofractionation, stereotactic body RT [SBRT]) and brachytherapy (BT), with an emphasis on the outcomes, toxicities, and contraindications for therapies. PICOS/PRISMA methods were used to identify published English-language comparative studies on PubMed (from 1980 to 2015) that included men treated on prospective studies with a primary endpoint of patient outcomes, with ⩾70 patients, and ⩾5year median follow up. Twenty-six studies met inclusion criteria; of these, 16 used EBRT, and 10 used BT. Long-term freedom from biochemical failure (FFBF) rates were roughly equivalent between conventional and hypofractionated RT with intensity modulation (evidence level 1B), with 10-year FFBF rates of 45-90%, 40-60%, and 20-50% (for low-, intermediate-, and high-risk groups, respectively). SBRT had promising rates of BF, with shorter follow-up (5-year FFBF of >90% for low-risk patients). Similarly, BT (5-year FFBF for low-, intermediate-, and high-risk patients have generally been >85%, 69-97%, 63-80%, respectively) and BT+EBRT were appropriate in select patients (evidence level 1B). Differences in overall survival, distant metastasis, and cancer specific mortality (5-year rates: 82-97%, 1-14%, 0-8%, respectively) have not been detected in randomized trials of dose escalation or in studies comparing RT modalities. Studies did not use patient-reported outcomes, through Grade 3-4 toxicities were rare (<5%) among all modalities. There was limited evidence available to compare proton therapy to other modalities. The treatment decision for a man is usually based on his risk group, ability to tolerate the procedure, convenience for the patient, and the anticipated impact on quality of life. To further personalize therapy, future trials should report (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education status; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics.

Effects of Time to Treatment on Biochemical and Clinical Outcomes for Patients With Prostate Cancer Treated With Definitive Radiation.

INTRODUCTION: The purpose of this study was to evaluate if time to treatment (TTT) has an effect on outcomes for patients with localized prostate cancer treated with definitive external beam radiation therapy (EBRT). PATIENTS AND METHODS: We included 4064 patients (1549 low-risk, 1612 intermediate-risk, and 903 high-risk) treated with EBRT. For each National Comprehensive Cancer Network (NCCN) risk group, TTT (defined as the time between initial positive prostate biopsy and start of RT) was analyzed in 4 intervals: < 3, 3-6, 6-9, and 9-24 months. We recorded the use of androgen deprivation therapy among patients with intermediate-risk and high-risk disease. RESULTS: The median TTT was 3.3 months (range, 0.6-23.5 months), and it was similar for each risk group (range, 3.3-3.4 months). The median follow up was 64 months. There were no significant differences in biochemical failure, distant metastasis, or overall survival for patients with TTT < 3, 3-6, 6-9, or 9-24 months for each risk group. There were also no significant differences in the outcomes at 5 years when patients with TTT > 3.3 months were compared with those with TTT ≤ 3.3 months for each risk group. For high-risk men, 328 of 450 (72.9%) with TTT > 3.3 months were on androgen deprivation therapy (ADT) versus 299 of 453 (66%) with TTT ≤ 3.3 months. Among men with high-risk cancer treated without ADT, there remained no significant difference in outcomes between TTT > 3.3 months and TTT ≤ 3.3 months. CONCLUSION: TTT was not associated with significant differences in outcomes among each risk group of men with localized prostate cancer treated with EBRT. Among the high-risk patients, there were no observed detriments in outcomes with TTT > 3.3 months regardless of androgen deprivation therapy use.

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

BACKGROUND: Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT. METHODS: The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 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 and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality. RESULTS: Of the 1442 patients identified, approximately 20% had a BMI <25 kg/m(2) , 48% had a BMI of 25 to 29.9 kg/m(2) , 23% had a BMI of 30 to 34.9 kg/m(2) , 6% had a BMI of 35 to 39.9 kg/m(2) , and 4% had a BMI of ≥40 kg/m(2) . The median follow-up was 47.6 months (range, 1-145 months), with a median age of 68 years (range, 36-89 years). The median dose was 78 grays (range, 76-80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age (P<.001) and pretreatment prostate-specific antigen level (P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02-1.08 [P = .004]). CONCLUSIONS: For patients with CaP receiving dose-escalated intensity-modulated RT with daily image-guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality.

Variation in external beam treatment plan quality: An inter-institutional study of planners and planning systems.

PURPOSE: This study quantifies variation in radiation treatment plan quality for plans generated by a population of treatment planners given very specific plan objectives. METHODS AND MATERIALS: A "Plan Quality Metric" (PQM) with 14 submetrics, each with a unique value function, was defined for a prostate treatment plan, serving as specific goals of a hypothetical "virtual physician." The exact PQM logic was distributed to a population of treatment planners (to remove ambiguity of plan goals or plan assessment methodology) as was a predefined computed tomographic image set and anatomic structure set (to remove anatomy delineation as a variable). Treatment planners used their clinical treatment planning system (TPS) to generate their best plan based on the specified goals and submitted their results for analysis. RESULTS: One hundred forty datasets were received and 125 plans accepted and analyzed. There was wide variability in treatment plan quality (defined as the ability of the planners and plans to meet the specified goals) quantified by the PQM. Despite the variability, the resulting PQM distributions showed no statistically significant difference between TPS employed, modality (intensity modulated radiation therapy versus arc), or education and certification status of the planner. The PQM results showed negligible correlation to number of beam angles, total monitor units, years of experience of the planner, or planner confidence. CONCLUSIONS: The ability of the treatment planners to meet the specified plan objectives (as quantified by the PQM) exhibited no statistical dependence on technologic parameters (TPS, modality, plan complexity), nor was the plan quality statistically different based on planner demographics (years of experience, confidence, certification, and education). Therefore, the wide variation in plan quality could be attributed to a general "planner skill" category that would lend itself to processes of continual improvement where best practices could be derived and disseminated to improve the mean quality and minimize the variation in any population of treatment planners.

Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02.

PURPOSE: Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity. METHODS AND MATERIALS: High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score >or=7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began. RESULTS: The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2. CONCLUSION: TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.