Prostate-Specific Antigen After Neoadjuvant Androgen Suppression in Prostate Cancer Patients Receiving Short-Term Androgen Suppression and External Beam Radiation Therapy: Pooled Analysis of Four NRG Oncology Radiation Therapy Oncology Group Randomized Clinical Trials.

PURPOSE: To validate whether prostate-specific antigen (PSA) level after neoadjuvant androgen suppression (neoAS) is associated with long-term outcome after neoAS and external beam radiation therapy (RT) with concurrent short-term androgen suppression (AS) in patients with prostate cancer. METHODS AND MATERIALS: This study included 2404 patients. The patients were treated with neoAS before RT and concurrent AS (without post-RT AS) and were pooled from NRG Oncology/RTOG trials 9202, 9408, 9413, and 9910. Multivariable models were used to test associations between the prespecified dichotomized post-neoAS, pre-RT PSA level (≤0.1 vs >0.1 ng/mL) groupings, and clinical outcomes. RESULTS: The median follow-up for surviving patients was 9.4 years. The median post-neoAS, pre-RT PSA level was 0.3 ng/mL, with 32% of patients having levels ≤0.1 ng/mL. Race, Gleason score, tumor stage, node stage, pretreatment PSA level, and duration of neoAS were associated with the groups of patients with PSA levels ≤0.1 and >0.1 ng/mL. In univariate analyses, post-neoAS, pre-RT PSA level >0.1 ng/mL was associated with increased risks of biochemical failure (hazard ratio [HR], 2.04; P < .0001); local failure (HR, 2.51; P < .0001); distant metastases (HR, 1.73; P = .0006); cause-specific mortality (HR, 2.36; P < .0001); and all-cause mortality (HR, 1.24; P = .005). In multivariable models that also included baseline and treatment variables, post-neoAS, pre-RT PSA level >0.1 ng/mL was independently associated with increased risk of biochemical failure (HR, 2.00; P < .0001); local failure (HR, 2.33; P < .0001); and cause-specific mortality (HR, 1.75; P = .03). CONCLUSIONS: Patients with a PSA level >0.1 ng/mL after neoAS and before the start of RT had less favorable clinical outcomes than patients whose PSA level was ≤0.1 ng/mL. The role of post-neoAS, pre-RT PSA level relative to PSA levels obtained along the continuum of medical care is not presently defined but could be tested in future clinical trials.

Sequence of hormonal therapy and radiotherapy field size in unfavourable, localised prostate cancer (NRG/RTOG 9413): long-term results of a randomised, phase 3 trial.

BACKGROUND: The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment. METHODS: The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial. FINDINGS: Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group. INTERPRETATION: In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT. FUNDING: National Cancer Institute.

Serum testosterone changes in patients treated with radiation therapy alone for prostate cancer on NRG oncology RTOG 9408.

OBJECTIVES: We reviewed testosterone changes for patients who were treated with radiation therapy (RT) alone on NRG oncology RTOG 9408. METHODS AND MATERIALS: Patients (T1b-T2b, prostate-specific antigen <20 ng/mL) were randomized between RT alone and RT plus 4 months of androgen ablation. Serum testosterone (ST) levels were investigated at enrollment, RT completion, and the first follow-up 3 months after RT. The Wilcoxon signed rank test was used to compare pre- and post-treatment ST levels in patients who were randomized to the RT-alone arm. RESULTS: Of 2028 patients enrolled, 992 patients were randomized to receive RT alone and 917 (92.4%) had baseline ST values available and completed RT. Of these 917 patients, immediate and 3-month post-RT testosterone levels were available for 447 and 373 patients, respectively. Excluding 2 patients who received hormonal therapy off protocol after RT, 447 and 371 patients, respectively, were analyzed. For all patients, the median change in ST values at completion of RT and at 3-month follow-up were -30.0 ng/dL (p5-p95; -270.0 to 162.0; P < .001) and -34.0 ng/dL (p5-p95, -228.0 to 160.0; P < .01), respectively. CONCLUSION: RT for prostate cancer was associated with a median 9.2% decline in ST at completion of RT and a median 9.3% decline 3 months after RT. These changes were statistically significant.

Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08.

BACKGROUND: Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease. OBJECTIVE: We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial. DESIGN, SETTING, AND PARTICIPANTS: A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA. RESULTS AND LIMITATIONS: Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p=0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death. CONCLUSIONS: Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit. PATIENT SUMMARY: We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit.

A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902.

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS). METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before RT plus an oral antiandrogen for 4 months before and during RT. The study was designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90% power and a 2-sided alpha of 0.05. RESULTS: A total of 397 patients (380 eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10 and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The median follow-up period was 9.2 years. The trial closed early because of excess thromboembolic toxicity in the CT arm. The 10-year results for all randomized patients revealed no significant difference between the AS + RT and AS + RT + CT arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or disease-free survival (22% vs 26%; P=.61). CONCLUSIONS: NRG Oncology RTOG 9902 showed no significant differences in OS, biochemical failure, local progression, distant metastases, or disease-free survival with the addition of adjuvant CT to LT AS + RT. The trial results provide valuable data regarding the natural history of high-risk PCa treated with LT AS + RT and have implications for the feasibility of clinical trial accrual and tolerability using CT for PCa.

Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer.

PURPOSE: We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. MATERIALS AND METHODS: From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (≥7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. RESULTS: The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. CONCLUSION: Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck.

PURPOSE: This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). METHODS AND MATERIALS: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm. RESULTS: A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. CONCLUSIONS: This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

Duration of androgen suppression before radiotherapy for localized prostate cancer: radiation therapy oncology group randomized clinical trial 9910.

PURPOSE: To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer. PATIENTS AND METHODS: One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up. RESULTS: There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively. CONCLUSION: Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy.

PURPOSE: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. MATERIALS AND METHODS: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. RESULTS: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). CONCLUSION: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Dose-escalated radiation therapy with and without short-course androgen deprivation for intermediate-risk prostate cancer.

AIM: To investigate outcomes in intermediate-risk (IR) prostate cancer patients receiving dose-escalated external beam radiation therapy (RT) with or without short-course androgen deprivation (ADT). PATIENTS AND METHODS: This study comprised of 203 patients with IR prostate cancer who were treated at a single institution to a dose of 7,560 cGy or more between 2003-2010. Of these, 62 (30.5%) patients received ADT. Biochemical recurrence, distant metastatic-free survival, prostate cancer-specific survival, and overall survival were analyzed using the Kaplan-Meier method. RESULTS: The median follow-up was 62 months and the median duration of ADT was 6 months. The 6-year biochemical control was 89.2% for those receiving RT plus ADT versus 76.7% in those receiving RT alone (p=0.02). There were no differences between the two groups regarding distant metastatic-free survival, prostate cancer-specific survival, and overall survival (respective p-values of 0.91, 0.50, 0.67). CONCLUSION: Dose-escalated RT and short-course ADT results in improved biochemical outcomes for IR prostate cancer.

Postoperative chemoradiotherapy and cetuximab for high-risk squamous cell carcinoma of the head and neck: Radiation Therapy Oncology Group RTOG-0234.

PURPOSE: To report results of a randomized phase II trial (Radiation Therapy Oncology Group RTOG-0234) examining concurrent chemoradiotherapy and cetuximab in the postoperative treatment of patients with squamous cell carcinoma of the head and neck (SCCHN) with high-risk pathologic features. PATIENTS AND METHODS: Eligibility required pathologic stage III to IV SCCHN with gross total resection showing positive margins and/or extracapsular nodal extension and/or two or more nodal metastases. Patients were randomly assigned to 60 Gy radiation with cetuximab once per week plus either cisplatin 30 mg/m(2) or docetaxel 15 mg/m(2) once per week. RESULTS: Between April 2004 and December 2006, 238 patients were enrolled. With a median follow-up of 4.4 years, 2-year overall survival (OS) was 69% for the cisplatin arm and 79% for the docetaxel arm; 2-year disease-free survival (DFS) was 57% and 66%, respectively. Patients with p16-positive oropharynx tumors showed markedly improved survival outcome relative to patients with p16-negative oropharynx tumors. Grade 3 to 4 myelosuppression was observed in 28% of patients in the cisplatin arm and 14% in the docetaxel arm; mucositis was observed in 56% and 54%, respectively. DFS in this study was compared with that in the chemoradiotherapy arm of the RTOG-9501 trial (Phase III Intergroup Trial of Surgery Followed by Radiotherapy Versus Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck), which had a hazard ratio of 0.76 for the cisplatin arm versus control (P = .05) and 0.69 for the docetaxel arm versus control (P = .01), reflecting absolute improvement in 2-year DFS of 2.5% and 11.1%, respectively. CONCLUSION: The delivery of postoperative chemoradiotherapy and cetuximab to patients with SCCHN is feasible and tolerated with predictable toxicity. The docetaxel regimen shows favorable outcome with improved DFS and OS relative to historical controls and has commenced formal testing in a phase II/III trial.

Impact of race in a predominantly African-American population of patients with low/intermediate risk prostate cancer undergoing radical prostatectomy within an equal access care institution.

PURPOSE: To study the impact of race in an equal access care institution with a predominantly African-American (AA) population. METHODS: We retrospectively reviewed data from 222 men with low risk (LR) or intermediate risk (IR) prostate cancer who underwent radical prostatectomy at the New York Harbor VA between 2003 and 2011. Biochemical relapse, distant control, and prostate cancer-specific survival were analyzed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox regression modeling was performed to determine the impact of covariates on biochemical outcome. RESULTS: Most patients (65.3 %) were AA. The median follow-up was 58 months, and 89.6 % of patients were followed for a minimum of 2 years after their surgery. Analyzing the whole cohort, the biochemical control was improved in Caucasian patients compared with AA (90.2 vs. 75.4 %, p = 0.008). On subgroup analysis, for IR disease, this difference was no longer significant, 80.5 % for Caucasians versus 69.8 % for AA (p = 0.36). However, for LR disease, the 5-year biochemical control remained significantly improved for Caucasians compared with AA, with a 5-year biochemical control of 97.6 versus 81.7 %, p = 0.006. On multivariate analysis, AA race was a significant predictor for biochemical recurrence (HR 2.69, 95 % CI 1.27-5.65, p = 0.009). There were no differences between the two groups regarding distant control (p = 0.14) or prostate cancer-specific survival (p = 0.29). CONCLUSIONS: In this predominant AA population with equal access to medical care, AA race is an independent predictor of biochemical recurrence after prostatectomy in men with LR or IR prostate cancer.

Concordance Between Prostate Needle Biopsy and Surgical Histopathology in a Primarily African-American Population.

INTRODUCTION: Prior studies have revealed that the concordance between biopsy and surgical specimens has been improving over time. However, to date, this has not been analyzed in an African American population, for whom data have often shown more aggressive prostate cancer than for other races. METHODS: We analyzed 250 patients who were operated on at the NY Harbor Department of Veterans Affairs for localized prostate cancer between 2003 and 2010. The clinical biopsy scores were compared with the pathological biopsy scores. We compared the concordance using the κ coefficient. Univariate and multivariate logistic regressions were used to identify predictors for poor concordance. RESULTS: This population consisted of 59.6% African Americans, 32% Caucasians, and 8.4% Hispanics. Overall, there was a 50% exact concordance between the biopsy and surgical specimens. The κ was 0.33, indicating fair agreement. Patients with a Gleason score of 6 were found to have an exact concordance 66% of the time, and those with a score of Gleason 7 (3 + 4) had an exact concordance 50% of the time. On univariate and multivariate analyses, only an increasing prostate-specific antigen was associated with reduced concordance. Race was not a significant predictor. CONCLUSIONS: These data are in line with prior studies of concordance. Despite being a population with more aggressive prostate cancer, there does not appear to be an increase in the risk of discordance in African American men.

Radiation therapy for clinically localized prostate cancer: long-term results of 469 patients from a single institution in the era of dose escalation.

AIMS: The aim of the following study is to analyze the long-term results of veterans treated with dose escalated radiation therapy for prostate cancer. MATERIALS AND METHODS: This retrospective study analyzed 469 patients who were treated between 2003 and 2010 with dose escalated radiation therapy to a minimum dose of 7560 cGy for prostate cancer at the New York Harbor Department of Veterans Affairs. Biochemical failure-free survival (bFFS) and distant metastatic-free survival (DMFS) were compared using the Kaplan-Meier method. Univariate and multivariate Cox Regression were used to measure the impact of covariates on biochemical control. RESULTS: The median follow-up was 61 months and 95.3% of patients were followed at least 2 years. The 5-year bFFS for National Cancer Care Network low, intermediate and high risk disease were 90.3%, 86.9% and 77.3% respectively (P=0.001). Patients with high risk disease were more likely to develop metastatic disease. The 5-year DMFS was 99.1% for low risk, 98.8% for intermediate risk and 94.5% for high-risk (P<0.001). There were 8 prostate cancer related deaths, of which 6 had high risk disease and 2 had intermediate risk disease. The 5-year prostate cancer specific survival was 98.4%. Toxicities were generally mild, however there were two genitourinary toxicity related deaths, though in both patients there were confounding medical issues that may have contributed to their deaths. CONCLUSIONS: Dose escalated radiation in the treatment of United States Veterans appears to be well-tolerated with results in line with prior reports. Further follow-up is necessary to identify any additional late toxicities as well as to assess the durability of their biochemical control beyond 5 years.

Outcomes and tolerance of human immunodeficiency virus--positive U.S. veterans undergoing dose-escalated external beam radiotherapy for localized prostate cancer.

INTRODUCTION: There are little data on the outcomes and tolerance, as well as the impact on the CD4 counts, of human immunodeficiency virus (HIV)-positive patients with prostate cancer who undergo high-dose external beam radiotherapy. MATERIALS AND METHODS: We identified 15 HIV-positive patients with prostate cancer who were treated with external beam radiation to a dose ≥ 75.6 Gy at the New York Harbor Department of Veterans Affairs between 2003 and 2010. Kaplan-Meier analyses were used to measure biochemical control outcomes. Toxicity and CD4 counts before, after, and during treatments were analyzed. RESULTS: A total of 15 patients were identified, with a median follow-up period of 49 months. There were 2 biochemical failures, which occurred at 28 months and 63 months, respectively. In neither of these 2 patients was there evidence of metastatic disease. The overall 5-year biochemical control was 92.3%. There appeared to be a consistent decline in the CD4 counts both during and immediately after the radiation treatments. Most of these patients had a subsequent improvement in their CD4 counts. Toxicity was mild overall, though there was 1 patient who developed rectal bleeding 11 months post treatment, which required argon plasma coagulation. CONCLUSION: Dose-escalated external beam radiation is well tolerated in HIV-positive patients with durable biochemical control and mild toxicity. A substantial decline in CD4 counts is associated with the radiation; therefore, these counts need to be monitored closely, in conjunction with the infectious-disease specialist.

Racial and socioeconomic disparities in the selection of prostate brachytherapy.

PURPOSE: To utilize the surveillance, epidemiology, and end results database to analyze whether there are racial or socioeconomic disparities associated with the selection of prostate brachytherapy. MATERIAL AND METHODS: We selected patients who were diagnosed with localized prostate cancer between 2004-2006 and who underwent treatment with radiation. Data regarding race and estimates of socioeconomic status were also obtained by analyzing the average reported cost of living adjusted income in the SEER county from which the patient was treated, and dividing these results into quartiles. Multivariate logistic regression analysis was used to determine whether there were any disparities associated with brachytherapy use. RESULTS: A total of 38 704 patients were included in the analysis. Most patients (57%) received EBRT alone, while the remaining 43% of patients had brachytherapy as a component of their treatment, either alone (30.2%) or in combination with EBRT (12.2%). On multivariate logistic regression, prostate brachytherapy use was less likely in African American patients with an odds ratio of 0.89 (95% CI: 0.84-0.95, p < 0.001), and was more likely to be used in those with higher socioeconomic status. Regarding socioeconomic status, the odds ratio for receiving brachytherapy was 1.65 (95% CI: 1.55-1.75) for the 25-50% quartile, 1.92 (95% CI: 1.81-2.04) for the 50-75% quartile, and 2.05 (95% CI: 1.93-2.18) for the 75-100% quartile, respectively (p < 0.001). CONCLUSIONS: There do appear to be socioeconomic and racial disparities in the selection of prostate brachytherapy. These findings may have both significant equality of care as well as cost of care implications.

A population-based comparison of overall and disease-specific survival following local excision or abdominoperineal resection for stage I rectal adenocarcinoma.

PURPOSE: The use of local excision (LE) for early stage rectal adenocarcinoma is increasing due to the associated morbidity of radical resection. To determine if survival in stage I rectal cancer differs following LE or abdominoperineal resection (APR), we analyzed the Surveillance, Epidemiology, and End Results Database. MATERIAL AND METHODS: We selected patients diagnosed between 1988 and 2002 with T1-2N0M0 rectal adenocarcinoma measuring ≤4 cm who underwent either local excision with (LE + RT) or without adjuvant radiation (LE alone) or APR alone. Overall survival (OS) and disease-specific survival (DSS) curves were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression was also performed to determine the effect of covariates on OS and DSS. RESULTS: A total of 2,391 patients were identified including 981 (41 %) treated with APR, 1,018 (43 %) treated with LE alone, and 392 (16 %) treated with LE + RT. With a median follow-up of 69 months, there was no difference in OS or DSS seen between the three groups (p > 0.05 for all comparisons). When stratifying by T-stage, there was a significant difference in overall survival between LE alone and APR for T2 disease. However, there was no difference in DSS between these two subgroups. There were no other significant survival differences between all comparable subgroups. CONCLUSIONS: In this large population-based study, there was no difference in long-term DSS between patients who underwent an APR compared to selected patients who underwent LE with or without adjuvant radiation. Although these data further reinforce the promising data regarding the selected use of LE, further prospective studies are needed to further elucidate the role of LE in this setting.

Characterization and outcomes of small cell carcinoma of the bladder using the surveillance, epidemiology, and end results database.

OBJECTIVE: To utilize the Surveillance, Epidemiology, and End Results Database to analyze clinical features, treatment, and survival outcomes of patients with small cell carcinoma of the bladder in a large population-based sample. Because of its rarity, prior reports are primarily limited to small single-institution studies. METHODS: We identified patients of any age who were diagnosed with small cell carcinoma of the bladder between 1988 and 2007. Kaplan-Meier and Cox regression analysis were used to compare overall survival (OS) and urinary bladder-specific survival. RESULTS: A total of 663 patients were identified. Most patients had either stage II (38.8%) or stage IV (35.4%) disease. The median OS for all patients was 12 months [95% confidence interval (CI), 10.9-13.1]. After excluding those patients who presented with distant metastatic disease or for whom it was unknown whether or not they received any treatment, there were no significant differences in survival between those that received cystectomy (median survival, 21 mo; 95% CI, 14.3-27.7) compared with those who underwent external beam radiation (median survival, 17 mo; 95% CI, 13.4-20.6). On multivariate analysis, both cystectomy (hazard ratio, 0.53; 95% CI, 0.4-0.71; P < 0.001) and radiation (hazard ratio, 0.66; 95% CI, 0.5-0.88; P=0.005) were associated with improved survival. CONCLUSIONS: Small cell carcinoma of the bladder is a rare but aggressive malignancy with poor OS. For those who present without widespread metastatic disease, treatment with either cystectomy or radiation appears to improve survival. Further prospective studies are needed to determine the best approach for treatment of these patients.

RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal.

PURPOSE: A multi-institutional phase 2 trial assessed the utility of dose-painted intensity modulated radiation therapy (DP-IMRT) in reducing grade 2+ combined acute gastrointestinal and genitourinary adverse events (AEs) of 5-fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer by at least 15% compared with the conventional radiation/5FU/MMC arm from RTOG 9811. METHODS AND MATERIALS: T2-4N0-3M0 anal cancer patients received 5FU and MMC on days 1 and 29 of DP-IMRT, prescribed per stage: T2N0, 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs) in 28 fractions; T3-4N0-3, 45 Gy elective nodal, 50.4 Gy ≤ 3 cm or 54 Gy >3 cm metastatic nodal and 54 Gy anal tumor PTVs in 30 fractions. The primary endpoint is described above. Planned secondary endpoints assessed all AEs and the investigator's ability to perform DP-IMRT. RESULTS: Of 63 accrued patients, 52 were evaluable. Tumor stage included 54% II, 25% IIIA, and 21% IIIB. In primary endpoint analysis, 77% experienced grade 2+ gastrointestinal/genitourinary acute AEs (9811 77%). There was, however, a significant reduction in acute grade 2+ hematologic, 73% (9811 85%, P=.032), grade 3+ gastrointestinal, 21% (9811 36%, P=.0082), and grade 3+ dermatologic AEs 23% (9811 49%, P<.0001) with DP-IMRT. On initial pretreatment review, 81% required DP-IMRT replanning, and final review revealed only 3 cases with normal tissue major deviations. CONCLUSIONS: Although the primary endpoint was not met, DP-IMRT was associated with significant sparing of acute grade 2+ hematologic and grade 3+ dermatologic and gastrointestinal toxicity. Although DP-IMRT proved feasible, the high pretreatment planning revision rate emphasizes the importance of real-time radiation quality assurance for IMRT trials.

Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck.

PURPOSE: Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes. METHODS AND MATERIALS: A total of 410 analyzable patients who had high-risk resected head-and-neck cancers were prospectively randomized to receive either radiation therapy (RT: 60 Gy in 6 weeks) or identical RT plus cisplatin, 100 mg/m(2)i.v. on days 1, 22, and 43 (RT + CT). RESULTS: At 10 years, the local-regional failure rates were 28.8% vs 22.3% (P=.10), disease-free survival was 19.1% vs 20.1% (P=.25), and overall survival was 27.0% vs 29.1% (P=.31) for patients treated by RT vs RT + CT, respectively. In the unplanned subset analysis limited to patients who had microscopically involved resection margins and/or extracapsular spread of disease, local-regional failure occurred in 33.1% vs 21.0% (P=.02), disease-free survival was 12.3% vs 18.4% (P=.05), and overall survival was 19.6% vs 27.1% (P=.07), respectively. CONCLUSION: At a median follow-up of 9.4 years for surviving patients, no significant differences in outcome were observed in the analysis of all randomized eligible patients. However, analysis of the subgroup of patients who had either microscopically involved resection margins and/or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy. The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT.