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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined.Methods: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes.Results: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy.Conclusions: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

To describe the clinical characteristics, treatment patterns and outcomes in advanced small cell bladder cancer ( aSCBC) patients and compare to those with urothelial carcinoma ( UC). Individuals in the National Cancer Data Base with a diagnosis of either nodal (TxN+M0) or distant metastatic (TxNxM1) disease were identified from 1998 to 2010. We assessed the relationships between stage, treatment modalities and survival in the aSCBC cohort and compared these to UC patients. In the 960 patient aSCBC cohort (62% M1), 50% received palliative therapy alone, 68% in M1 versus 21% in M0 groups ( P < 0.0001). Single modality local therapy (15%) and surgical (21%) or radiation-based (14%) multimodal therapy ( MMT) were used in the other 50%. Cystectomy-based MMT was utilized in 45% of N+M0 versus 6.4% of NxM1 patients ( P < 0.0001). Median overall survival ( OS) for aSCBC patients was 8.6 months; 13.0 months in N+M0 versus 5.3 months in NxM1 patients ( P < 0.0001). Survival was similar between TxN1M0 and TxN2-3M0 patients (14.8 months vs. 12.1 months, P = 0.15). Urothelial carcinoma patients ( n = 27,796, 45% M1) lived longer compared to aSCBC patients in the N+M0 group (17.3 months vs. 13.0 months, P = 0.0007). There were not clinically significant differences in OS between UC and aSCBC patients in the M1 group. Advanced SCBC is a rare disease with a poor survival and palliative therapy is common, especially in M1 patients. In comparison to UC, the outcomes for aSCBC patients are worse in those with lymph node only involvement but similar in those with distant disease. [ABSTRACT FROM AUTHOR]

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/m2, 48% had a BMI of 25 to 29.9 kg/m2, 23% had a BMI of 30 to 34.9 kg/m2, 6% had a BMI of 35 to 39.9 kg/m2, and 4% had a BMI of ≥40 kg/m2. 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. Cancer 2015;121:3010-3017. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Brachytherapy has been shown to be an efficacious and cost-effective treatment among patients with localized prostate cancer. In this study, the authors examined trends in brachytherapy use for localized prostate cancer using a large national cancer registry. METHODS In the National Cancer Data Base (NCDB), a total of 1,547,941 patients with localized prostate cancer were identified from 1998 through 2010. Excluding patients with lymph node-positive or metastatic disease, the authors examined primary treatment trends focusing on the use of brachytherapy over time. Patients with available data (2004-2009) were stratified by National Comprehensive Cancer Network risk criteria. Controlling for year of diagnosis and demographic, clinical, and pathologic characteristics, multivariate analyses were performed examining the association between patient characteristics and receipt of brachytherapy. RESULTS In the study cohort, brachytherapy use reached a peak of 16.7% in 2002, and then steadily declined to a low of 8% in 2010. Of the 719,789 patients with available data for risk stratification, 41.1%, 35.3%, and 23.6%, respectively, met low, intermediate, and high National Comprehensive Cancer Network risk criteria. After adjustment, patients of increasing age and those with Medicare insurance were more likely to receive brachytherapy. In contrast, patients with intermediate-risk or high-risk disease, Medicaid insurance, increasing comorbidity count, and increasing year of diagnosis were less likely to receive brachytherapy. CONCLUSIONS For patients with localized prostate cancer who are treated at National Cancer Data Base institutions, there has been a steady decline in brachytherapy use since 2003. For low-risk patients, the declining use of brachytherapy monotherapy compared with more costly emerging therapies has significant health policy implications. Cancer 2014;120:2114-2121. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Randomized trials have demonstrated that escalated-dose external-beam radiotherapy (EDRT) is better than standard-dose radiotherapy (SDRT) for patients with prostate cancer and that adding androgen-deprivation therapy (ADT) to SDRT is better than SDRT alone; however, no trials have compared EDRT versus SDRT plus ADT or EDRT versus EDRT plus ADT. The authors designed a model to estimate the results of various doses of radiotherapy (RT) combined with various durations of ADT. METHODS: From 1989 to 2007, 3215 men consecutively received definitive EDRT with or without ADT. In total, 2012 patients had complete records available for creating the nomogram. The duration of ADT varied for patients who received no RT (n = 1562), ≤6 months of RT (n = 145), from >6 months to <24 months of RT (n = 140), and ≥24 months of RT (n = 165) with a median follow-up of 65.7 months, 66.2 months, 60.1 months, and 63 months, respectively. The model included the following covariates: palpation T-category, biopsy Gleason score, the percentage of tumor cells with a Gleason pattern of 4 or 5, the percentage of tumor tissue, initial pretreatment prostate-specific antigen (PSA) level, ADT duration, and RT dose. Two nomograms, for outcomes with and without ADT, were created from a single competing-risks model. Biochemical failure was defined as a rise in serum PSA of 2 ng/mL over the post-treatment PSA nadir. RESULTS: According to the results from analyzing representative intermediate-risk to high-risk patient parameters, the gains from increasing the RT dose from 70 Gray (Gy) to 80 Gy were far less than the gains from adding ≥3 months of ADT. CONCLUSIONS: The nomograms provided unique patient-specific estimates of the effects of various doses and durations of RT and ADT. The results indicated that adding ADT to treatment for intermediate-risk and high-risk prostate cancer is far more beneficial than a modest RT dose escalation. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective of this study was to compare the prognostic value of the sixth and seventh editions of the American Joint Cancer Committee (AJCC) Cancer Staging Manual and the risk-stratification model of the National Comprehensive Cancer Network (NCCN). METHODS: Two-thousand four hundred twenty-nine men who received definitive radiotherapy with or without androgen-deprivation therapy (median follow-up, 74 months) were analyzed. RESULTS: There was a migration of stage II patients to stage I with AJCC seventh edition (stage I increased from 1% to 38%, and stage II decreased from 91% to 55%). One pair-wise comparison (4%) of Kaplan-Meier estimates of biochemical failure, distant metastasis, prostate cancer-specific survival, and overall survival between stages was statistically significant for the AJCC sixth edition. Conversely, 16 of 24 comparisons (67%) were significant for the AJCC seventh edition. With the NCCN risk-stratification model, 9 of 12 comparisons (75%) were significant. Concordance probability estimate (CPE) and standard error (SE) analysis indicated uniform and significant improvement in the predictive power of the AJCC seventh edition versus the sixth edition for all outcomes. CPE ± SE values for the AJCC seventh edition versus the sixth edition were 0.51 ± 0.009 versus 0.59 ± 0.02, respectively, for biochemical failure; 0.54 ± 0.02 versus 0.70 ± 0.05, respectively, for distant metastasis; 0.57 ± 0.009 versus 0.76 ± 0.007, respectively, for prostate cancer-specific survival; and 0.52 ± 0.006 versus 0.57 ± 0.01, respectively, for overall survival. CPE ± SE values for the NCCN model were 0.59 ± 0.02 for biochemical failure, 0.72 ± 0.05 for distant metastasis, 0.80 ± 0.01 for prostate cancer-specific survival, and 0.57 ± 0.01 for overall survival. CONCLUSIONS: The current results indicated that the seventh edition of the AJCC Cancer Staging Manual is a major improvement over the sixth edition, because it distributes patients better among the stages and is more prognostic. However, the NCCN model was superior to the AJCC seventh edition and remains the preferred method for risk-based clinical management of prostate cancer with radiotherapy. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The long-term survival of patients with high-risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen-deprivation therapy (ADT). METHODS: In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate-specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow-up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer-specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk-regression model. RESULTS: The 10-year cancer-specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51-1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68-1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all-cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25-2.05; P = .0002). CONCLUSIONS: RRP alone and EBRT plus ADT provided similar long-term cancer control for patients with high-risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality-of-life and noncancer mortality will be necessary to determine the optimal management approach for these patients. [ABSTRACT FROM AUTHOR]

The article focuses on a study which compared the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix biochemical failure (BF) estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). The patients included in the study were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The study observed BF in 389 men using the Phoenix definition and 460 men using the ASTRO definition.

Background: The relation of prostate cancer risk-group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. The authors hypothesized that early failures due to subclinical micrometastasis at presentation could be differentiated from late failures due to local persistence.Methods: A total of 1833 men with clinically localized prostate cancer treated with 3D-conformal radiotherapy with or without short-term androgen deprivation were retrospectively analyzed. By using American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (Nadir+2) definitions (developed at the ASTRO-RTOG [Radiation Therapy Oncology Group] consensus meeting, Phoenix, Arizona, January 21, 2005), the interval hazard rates of BF and DM were determined for men with low-risk, intermediate-risk, and high-risk disease.Results: Median follow-up was 67 months. Multivariate analysis showed that increasing risk group was independently associated with higher ASTRO BF (P < .0001) and Nadir+2 BF (P < .0001). The preponderance (87%) of ASTRO BF occurred 4 years. The hazard of Nadir+2 BF persisted in Years 8-12 in all risk groups. The interval hazard function for DM appeared to be biphasic (early peak followed by a drop and late increase) for intermediate-risk and high-risk patients, but no distinct early wave was evident for low-risk patients.Conclusions: Because of backdating, ASTRO BF underestimates late BF. Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent late DM in every risk group. The paucity of early DM among those with low-risk tumors supports the hypothesis that occult micrometastases contributed to the early wave. [ABSTRACT FROM AUTHOR]

Background: Ductal carcinoma of the prostate is a rare variant of prostate cancer that presents most commonly with obstructive urinary symptoms or hematuria. This case series of 6 patients is the first to report the outcome of ductal carcinoma treated with external beam radiotherapy.Methods: A retrospective review was performed of patients treated between 1980 and 2006 at Fox Chase Cancer Center, Philadelphia, Penn. Six patients were identified with ductal carcinoma.Results: Five of the 6 patients were treated definitively and the sixth patient was treated at recurrence 3 years after a radical prostatectomy. Patient ages ranged from 66-80 years and the initial prostate-specific antigen (iPSA) ranged from 1.69-100.3 ng/mL. Three patients had a mixed acinar and ductal carcinoma, 2 with a Gleason score (GS) of 8 and 1 with a GS of 7. Of the patients treated definitively, 4 had clinical stage T2A-T2C and 1 had clinical stage T1B. Definitive radiotherapy was delivered to the prostate with doses between 72 Gy and 78 Gy. Pelvic lymph nodes were treated in all patients. One patient was treated postradical prostatectomy to the prostate bed to a dose of 60 Gy. Adjuvant androgen deprivation was given in 5 of the patients. Two of the patients died from metastatic disease at 1.4 and 7.1 years after treatment. The remaining 4 patients remain alive between 3.2 and 4.8 years from treatment, with 3 patients biochemically without evidence of disease. No patients have developed a local recurrence.Conclusions: Ductal carcinoma of the prostate may be treated effectively with external beam radiotherapy. Aggressive management is indicated, even with low-volume metastatic disease. [ABSTRACT FROM AUTHOR]

Background: The nadir prostate-specific antigen (PSA) at 1 year (nPSA12) was investigated as an early estimate of biochemical and clinical outcome after radiotherapy (RT) alone for localized prostate cancer.METHODS.From May 1989 to November 1999, 1000 men received 3D conformal RT alone (median, 76 Gy) with minimum and median follow-up periods of 26 and 58 months, respectively, from the end of treatment. The calculation of PSA doubling time (PSADT) was possible in 657 patients. Multivariate analyses (MVAs) via Cox proportional hazards regression were used to determine the association of nPSA12 to biochemical failure (BF; ASTRO definition), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). Dichotomization of nPSA12 was optimized by evaluating the sequential model likelihood ratio and P-values.RESULTS.In MVA, nPSA12 as a continuous variable was independent of RT dose, T-stage, Gleason score, pretreatment initial PSA, age, and PSADT in predicting for BF, DM, CSM, and OM. Dichotomized nPSA12 (2 versus >2 ng/mL) was independently related to DM and CSM. Kaplan-Meier 10-year DM rates for nPSA12 2 versus >2 ng/mL were 4% versus 19% (P<.0001).CONCLUSIONS.nPSA12 is a strong independent predictor of outcome after RT alone for prostate cancer and should be useful in identifying patients at high risk for progression to metastasis and death. [ABSTRACT FROM AUTHOR]

To compare the outcome of similar patients with prostate cancer treated by either observation or three-dimensional conformal radiation therapy (3-DCRT). The study included 69 patients with nonmetastatic prostate cancer who were observed only; the indications included indolent disease, significant medical comorbidities and refusal of treatment. Of these, 62 patients had palpable T1–T2a and seven T2b–T3a disease, a median Gleason score of 6 and a median initial prostate-specific antigen (PSA) level of 5.3 ng/mL. A matched-cohort analysis of 69 patients, based on palpation T category, Gleason score and initial PSA, was used to compare the outcome between the observation and 3-DCRT groups. The median radiation dose for latter was 72 Gy. The median follow-up for the observed patients was 49 months. The 5- and 8-year actuarial rates of freedom from distant metastases were 100% and 93%, respectively, and the actuarial overall survival rates 94% and 73%, respectively. Seven observed patients had local disease progression on physical examination. Four patients who initially were observed received radiation therapy later for a rising PSA and/or local disease progression. For the 69 matched 3-DCRT patients, the overall 5-year rate for no biochemically evident disease was 74%. The respective 5- and 8-year actuarial rates of freedom from distant metastases were 95% and 95%, and actuarial overall survival rates 95% and 75%. There were no significant differences in distant metastasis and overall survival rates between the groups, and no deaths from prostate cancer in either group. Observation is a reasonable alternative to treatment in selected patients. During the 5-year follow-up the progression rates were relatively low, and there was no difference in distant metastasis or overall survival between the groups. As the follow-up was short a longer follow-up is needed to determine whether the outcome of those patients who chose observation will remain comparable to that in those undergoing immediate 3-DCRT. [ABSTRACT FROM AUTHOR]

Men with non-metastatic prostate cancer have many treatment options. For over 35 years, radiation therapy has been a mainstay of treatment for this disease. With improvements in technology and better use of pretreatment prognostic factors, such as prostate specific antigen level and Gleason score, biochemical and clinical results have steadily improved. This article reviews the current status of radiation therapy in the treatment of prostate cancer. Results of treatment utilizing three-dimensional conformal and conventional techniques are compared and contrasted. The appropriate use of adjuvant hormones and particle beam therapy in the management of this disease is also discussed. Finally, the toxicity and future directions of radiation therapy in the treatment of prostate cancer are addressed. [ABSTRACT FROM AUTHOR]