Using a surgical prostate-specific antigen threshold of >0.2 ng/mL to define biochemical failure for intermediate- and high-risk prostate cancer patients treated with definitive radiation therapy in the ASCENDE-RT randomized control trial

PurposeTo compare biochemical failure using a prostate-specific antigen (PSA) threshold of >0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL).Methods and MaterialsAndrogen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of >0.2 ng/mL.ResultsCompared to nadir+2 ng/mL, the >0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the >0.2 ng/mL threshold (p < 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (>0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319).ConclusionsReplacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.     

Assessing the impact of brachytherapy boost and androgen deprivation therapy on survival outcomes for patients with unfavorable intermediate-risk prostate cancer patients treated with external beam radiotherapy

BACKGROUNDCurrent recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa.MATERIALS AND METHODSThe National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (n = 13,265), EBRT+ADT (n = 13,123), EBRT+BT (n = 3440), or EBRT+BT+ADT (n = 2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios.RESULTSMedian follow-up was 60 months (range: 3–168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87–0.98], p = 0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69–0.85], p = 3 × 10^?7) and EBRT+BT+ADT (HR: 0.75 [0.67–0.83], p = 6 × 10^?8) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, p = 0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87–1.11], p = 0.82).CONCLUSIONSIn a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS.     

125I Interstitial brachytherapy with or without androgen deprivation therapy among unfavorable-intermediate and high-risk prostate cancer

PURPOSE/OBJECTIVE(S)To determine if patients with unfavorable intermediate-risk (UIR), high-risk (HR), or very high-risk (VHR) prostate cancer (PCa) treated with ¹²⁵I interstitial brachytherapy benefit from androgen deprivation therapy (ADT).MATERIALS/METHODSWe reviewed our institutional database of patients with UIR, HR, or VHR PCa, per 2018 NCCN risk classification, treated with definitive ¹²⁵I interstitial brachytherapy with or without ADT from 1998?2017. Outcomes including biochemical failure (bF), distant metastases (DM), and overall survival (OS) were analyzed with the Kaplan-Meier method and Cox proportional hazards regression. PCa-specific mortality (PCSM) was analyzed with Fine-Gray competing-risk regression.RESULTSOf 1033 patients, 262 (25%) received ADT and 771 (75%) did not. Median ADT duration was 6 months. By risk group, 764 (74%) patients were UIR, 219 (21%) HR, and 50 (5%) VHR. ADT was more frequently given to HR (50%) and VHR (56%) patients compared to UIR (16%; p<0.001), to older patients (p<0.001), corresponding with increasing PSA (p<0.001) and Grade Group (p<0.001). Median follow-up was 4.9 years (0.3?17.6 years). On multivariable analysis accounting for risk group, age, and year of treatment, ADT was not associated with bF, DM, PCSM, or OS (p≥0.05 each).CONCLUSIONAmong patients with UIR, HR, and VHR PCa, the addition of ADT to ¹²⁵I interstitial brachytherapy was not associated with improved outcomes, and no subgroup demonstrated benefit. Our findings do not support the use of ADT in combination with ¹²⁵I interstitial brachytherapy. Prospective studies are required to elucidate the role of ADT for patients with UIR, HR, and VHR PCa treated with prostate brachytherapy.     

Assessing the role of external beam radiation therapy in combination with brachytherapy versus brachytherapy alone for unfavorable intermediate-risk prostate cancer

BACKGROUNDDefinitive treatment options for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost ± androgen deprivation therapy (ADT). The role of brachytherapy ± ADT in the absence of EBRT is not well defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to BT±ADT for UIR-PCa.METHODS AND MATERIALSMen with UIR-PCa diagnosed between 2004 and 2015 were identified in the National Cancer Database (NCDB). Inverse propensity of treatment weighting was used to balance covariables that influenced treatment allocation and outcomes, and propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare OS hazard ratios.RESULTSA total of 11,721 men were stratified into four treatment groups: (1) BT without ADT (n = 4,535), (2) BT+ADT (n = 1,303), (3) EBRT+BT (n = 3,446), or (4) EBRT+BT+ADT (n = 2,437). Relative to patients treated with BT alone, BT+ADT (Hazard Ratio (HR): 0.86 [95% Confidence Interval (CI): 0.76–0.99], p = 0.03), EBRT+BT (HR: 0.79 [0.70–0.88], p = 0.00002), and EBRT+BT+ADT (HR: 0.76 [0.67–0.85], p = 0.000003) were associated with improved OS on MVA. Relative to BT alone, EBRT+BT correlated with improved OS on weight-adjusted MVA (HR: 0.82 [0.75–0.89], p = 0.000005). 10-year OS for BT vs. EBRT+BT was 62.4% [60.1–64.7] vs. 69.3% [67.5–71.2], respectively (p < 0.0001).CONCLUSIONSEBRT+BT correlated with improved OS relative to BT alone in men with UIR-PCa, reaffirming current NCCN recommendations recommending EBRT+BT over BT alone. While prior studies reported no benefit to adding EBRT to BT with optimal implant dosimetry, this study suggests men benefit from EBRT in a population of variable implant quality.     

Treatment of intermediate-risk prostate cancer with Cs-131: Long-term results from a single institution

PURPOSETo evaluate our institutional outcomes utilizing Cs-131 prostate brachytherapy (PB) for the intermediate-risk (IR) group of prostate cancer patients.METHODS AND MATERIALSWe reviewed a prospectively collected database of men treated with Cs-131 PB between 2006 and 2019. Patients with less than 24-months follow-up were excluded. Patients were classified as IR if they had one of the following factors: Gleason Score 7, prostate specific antigen >10 but <20 ng/mL, or T2b-c on clinical exam. We defined unfavorable-IR (UIR) as having either Grade Group 3, >1 IR factors, or ≥50% positive core biopsies. The Kaplan-Meier method was used to estimate actuarial event-time probabilities for biochemical freedom from disease (BFD).RESULTSA total of 335 patients with a median follow-up of 70.1 months (IQR 48.3–106.3 months) were identified. Androgen deprivation therapy (ADT) was used in 7.2% of patients. Favorable-IR (FIR) patients were commonly treated with PB alone (91.8%). FIR patients who underwent PB alone had a 5-year BFD of 98.1%. UIR patients were commonly treated with external beam radiotherapy plus PB (61.2%). These patients had 5-year BFD of 91.1%. The 5-year BFD for UIR patients treated without ADT was 90.9%, whereas it was 95.0% among UIR patients treated with ADT (log-rank p = 0.83).CONCLUSIONSFIR patients have excellent outcomes when treated with PB alone. External beam radiotherapy plus PB is a reasonable treatment approach for UIR patients. Future studies may elucidate which IR patients would benefit from treatment intensification.     

Association of Brachytherapy Boost with Overall Survival for Gleason 9-10 Prostate Cancer: The Impact of Primary versus Secondary Pattern 5

PURPOSEThe addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear.METHODSMen with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8−2.0 Gy per fraction) ≥74 Gy or moderately hypofractionated (2.5−3.0 Gy per fraction) ≥60 Gy. EBRT + BT group received conventionally fractionated ≥45 Gy or moderately hypofractionated ≥37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results.RESULTSA total of 8260 men were eligible: EBRT alone (89%) versus EBRT + BT (11%). 5-year OS for EBRT versus EBRT + BT was 76.3% and 85.0%, respectively (p = 0.002; multivariable adjusted HR 0.84, 95% CI 0.65−0.98; p = 0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4 + 5 PCa (p = 0.001) and not observed in men with Gleason 5 + 5 or 5 + 4 PCa.CONCLUSIONSExtent of pattern five may be useful in appropriately selecting men for EBRT+BT and should be considered as a pre-randomization stratification variable for future clinical trial design.     

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer

PurposeRetrospective data suggest less benefit from androgen deprivation therapy (ADT) in the setting of dose-escalated definitive radiation for prostate cancer, especially when a combination of external beam radiotherapy (EBRT) and brachytherapy approaches are used. This study aimed to test the hypothesis that patients with prostate cancer with intermediate- or high-risk disease undergoing extreme dose escalation with a brachytherapy boost are less likely to receive ADT.Methods and MaterialsData from the National Cancer Database were extracted for men aged 40–90 years diagnosed with node-negative, non-metastatic prostate cancer from 2004 to 2015. Only patients with intermediate- or high-risk disease who were treated with definitive radiotherapy were included. The association and patterns of care between dose escalated radiotherapy and ADT receipt were assessed using multivariable logistic regression.ResultsPatients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive ADT if they underwent dose escalation with a combination of EBRT and brachytherapy (odds ratio 0.67, p < 0.0001). Over time, this decrease in ADT utilization has widened for patients with unfavorable intermediate-risk disease. There was no difference in ADT utilization when comparing patients treated with non–dose-escalated EBRT to those treated with dose-escalated EBRT (without brachytherapy).ConclusionIn this large national database, patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive guideline-indicated ADT if they underwent extreme dose escalation with combined radiation modalities. As we await prospective data guiding the utility of ADT with dose escalated radiation, these findings suggest potential underutilization of ADT in patients at higher risk of advanced disease.     

Long-term outcomes analysis of low-dose-rate brachytherapy in clinically T3 high-risk prostate cancer

PurposeThe available data demonstrating that superiority of LDR brachytherapy (LDR-BT) boost in high-risk prostate cancer patients under represents patients with extracapsular extension (T3a) and/or seminal vesicle invasion (T3b) have been limited. We report long-term clinical outcomes data for patients with cT3a/b disease receiving LDR-BT.Methods and MaterialsNinety-nine men (median age: 69.4 years) with cT3a/bN0M0 high-risk prostate adenocarcinoma received definitive LDR-BT or LDR-BT boost after external beam radiation therapy (EBRT) at a single institution between 1998 and 2007. About 86% of patients received androgen deprivation therapy. Freedom from biochemical failure (FFBF), prostate cancer–specific survival (PCSS), and overall survival (OS) was calculated using the Kaplan–Meier method with the Phoenix definition used as definition of failure. Cox regression analysis was used to compare outcomes between clinical stage, initial PSA, Gleason Score, and percent core positive rate.ResultsWith a median followup of 7 years, 7-year rate of FFBF, PCSS, and OS for the entire cohort was 65.2% (±5.6%), 90.1% (±3.6%), and 77.9% (±4.7%), respectively. LDR-BT boost patients achieved a 7-year FFBF rate of 73.5 (±6.5%). No significant difference in outcomes was present between T3a or T3b disease, Gleason score, iPSA stratification and percent core positive rates.ConclusionsLDR-BT, primarily as a boost in conjunction with ADT and EBRT, is not only feasible, but also highly effective in men with cT3a and cT3b high-risk prostate cancer resulting in excellent biochemical control and survival outcomes. LDR-BT boost implantation of patients should be strongly considered for cT3 patients given the merits of trimodality care.     

A comparison of early prostate-specific antigen decline between prostate brachytherapy and different fractionation of external beam radiation—Impact on biochemical failure

PurposeThe aim of this study was to compare early prostate-specific antigen (PSA) decline patterns and PSA nadirs between low-dose-rate seed prostate brachytherapy (LDR-PB) and different fractionations of external beam radiotherapy (EBRT) and their predictive importance for biochemical failure (bF).Methods and MaterialsPatients with D'Amico low- or intermediate-risk prostate cancer who underwent a single-modality treatment without androgen deprivation were included in this study. Three different treatment groups were compared: (1) normofractionation EBRT up to 70.2–79.2 Gy/1.8–2.0 Gy, (2) LDR-PB, and (3) EBRT with hypofractionation 60 Gy/3 Gy daily or 5–7.25 Gy once a week over 9–5 weeks, to a total dose of 45–36.25 Gy, respectively. The log-rank test, Cox regression analysis, and nonparametric tests were used.ResultsWe analyzed 892 patients: the median followup for patients without bF was 84 months (interquartile range 60–102 months), with 12% of patients experiencing bF. The PSA decline within the first 15 months was generally exponential. LDR-PB showed a faster early exponential decline compared with EBRT treatments, but whether decline was fast or slow had no influence on recurrence. The only factors that were positive predictive factors in univariate and multivariate analyses were the time to nadir >48 months (median), PSA nadir <0.5 ng/mL, and <0.2 ng/mL (all p < 0.001).ConclusionsAlthough there are significant differences in early exponential PSA decline between different treatments, only the PSA nadir and longer time to nadir were predictive factors for bF.     

Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results

BackgroundSalvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy.Methods and MaterialsA total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received ¹²⁵I brachytherapy after attempted placement of 10 cc of a diluted hydrogel spacer between the prostate and rectum.ResultsSpacing was achieved in 8 of the 11 (73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9 mm (prior EBRT) vs. 7.7 mm (prior brachytherapy), p = 0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node–positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL.ConclusionHydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL.     

Detection of failure patterns using advanced imaging in patients with biochemical recurrence following low-dose-rate brachytherapy for prostate cancer

PURPOSE/OBJECTIVE(S)This study describes the pattern of failure in patients with biochemical (BCR) recurrence after low-dose-rate (LDR) brachytherapy as a component of definitive treatment for prostate cancer.METHODSPatients with BCR after LDR brachytherapy ± external beam radiation therapy (EBRT) were enrolled on prospective IRB approved advanced imaging protocols. Patients underwent 3T multiparametric MRI (mpMRI); a subset underwent prostate specific membrane antigen (PSMA)-based PET/CT. Pathologic confirmation was obtained unless contraindicated.RESULTSBetween January 2011 and April 2021, 51 patients with BCR after brachytherapy (n = 36) or brachytherapy + EBRT (n = 15) underwent mpMRI and were included in this analysis. Of 38 patients with available dosimetry, only two had D90<90%. The prostate and seminal vesicles were a site of failure in 66.7% (n = 34) and 39.2% (n = 20), respectively. PET/CT (n = 32 patients) more often identified lesions pelvic lymph nodes (50%; n = 16) and distant metastases (18.8%; n = 6), than mpMRI. Isolated nodal disease (9.8%; n = 5) and distant metastases (n = 1) without local recurrence were uncommon. Recurrence within the prostate was located in the transition zone in 48.5%, central or midline in 45.5%, and anterior in 36.4% of patients.CONCLUSIONIn this cohort of patients with BCR after LDR brachytherapy ± EBRT, the predominant recurrence pattern was local (prostate ± seminal vesicles) with frequent occurrence in the anterior prostate and transition zone. mpMRI and PSMA PET/CT provided complementary information to localize sites of recurrence, with PSMA PET/CT often confirming mpMRI findings and identifying occult nodal or distant metastases.     

Pride or prejudice: Does Phoenix flatter radiation therapy?

PurposeTo compare disease-free survival (DFS) rates using a >0.4 ng/mL biochemical failure definition with the Phoenix (nadir+2 ng/mL) failure definition by analyzing a consecutive cohort of 1006 patients treated with low-dose-rate prostate brachytherapy (LDR-PB) monotherapy.Methods and MaterialsData for first 1006 consecutive LDR-PB implants (1998–2003) were extracted from a prospective database. Patients had low- (58%) or intermediate (42%)-risk disease. Three months neoadjuvant and 3 months concomitant androgen deprivation therapy were used in 65% of cases. The Phoenix definition was modified to “unfail” patients who had a benign prostate-specific antigen (PSA) bounce.ResultsThe median followup is 7.5 years. The median PSA at latest followup for disease-free patients was 0.04 ng/mL. The Phoenix definition yielded 5- and 10-year Kaplan–Meier DFS estimates of 96.5 ± 1.2% and 93.7 ± 2.0%, respectively. Applying the >0.4 ng/mL threshold reduced these estimates to 94.4 ± 1.6% and 88.8 ± 3.0% (log rank, p = 0.015).ConclusionsCompared with Phoenix, applying a >0.4 ng/mL failure definition increased biochemical failure by ∼2% at 5 years and ∼5% at 10 years. These data show that Phoenix did not greatly exaggerate DFS estimates compared with a surgical-type threshold. However, this observation is a consequence of the exceptionally low residual PSA values characteristic of LDR-PB and cannot be generalized to other forms of radiation therapy.     

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score–matched analysis

PurposeThe purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer.Methods and MaterialsOverall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan–Meier curves, and predictors were identified using Cox proportional hazards regression models.ResultsAfter propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58–4.03) and ADT use (HR: 0.55, 95% CI: 0.34–0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16–0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08–1.16) and comorbidities (HR: 1.56, 95% CI: 1.04–2.34) were associated with all-cause mortality.ConclusionsA risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.     

Development,implementation, and outcomes of a simulation-based medical education (SBME) prostate brachytherapy workshop for radiation oncology residents

PurposeDespite a preponderance of data demonstrating strong clinical outcomes and cost-effectiveness, prostate brachytherapy use and competency continue to decline. Enhanced resident education may help reverse this trend. We therefore developed and implemented a simulation-based medical education course for low-dose-rate prostate brachytherapy (LDR-PB).Materials and MethodsA 1-week LDR-PB course comprised four 1-h lectures on clinical outcomes, physics, radiobiology, and anatomy/contouring, followed by a 4.5-h simulation session on ultrasound-guided prostate phantom implantation, was developed for radiation oncology residents at an academic institution. A 10-statement Likert-scale survey and 20-question multiple-choice test were administered 1 week before and 4 weeks after the course.ResultsPrecourse and postcourse instruments were completed by 24 and 20 residents, respectively. The median number of prior LDR-PB cases after at least one genitourinary rotation was 10.5 (range 5–20). Overall mean test scores were significantly improved (55% before the course vs 68% after the course; p = 0.010). Mean Likert scores significantly increased on nine of 10 survey statements and were significantly increased overall (2.4 before the course vs 3.3 after the course, p < 0.001). When asked about interest in performing brachytherapy after residency, 37.5% of residents “agreed” or “strongly agreed” before the course vs 50% after the course (p = 0.41). Those with higher postresidency brachytherapy interest (scores of 4–5 vs 1–3) had significantly more LDR-PB cases (11.2 vs 5.3 cases; p = 0.005).ConclusionsA 1-week simulation-based medical education course for LDR-PB can improve didactic performance and self-reported technical competence/confidence, and may increase overall enthusiasm for brachytherapy. Future studies at our institution will incorporate evaluation of implant quality and assessment of procedural competence into this framework. Residency programs should dedicate resources to this essential component of radiation oncology.     

Impact of radiotherapy modalities on outcomes in the adjuvant management of uterine carcinosarcoma: A National Cancer Database analysis

PurposeIn the postoperative management of uterine carcinosarcoma (UCS), the roles of individual radiotherapy (RT) modalities, chiefly external-beam radiotherapy (EBRT) and brachytherapy (BT), remain undefined. We analyzed the survival impact of EBRT and BT using the National Cancer Database.Methods and materialsWe abstracted women diagnosed with UCS from 2004 to 2012 who received hysterectomy and had complete RT information. Cox multivariate analysis and propensity-score matched analyses were used to compare survival among radiotherapeutic approaches.ResultsWe identified 1229 women receiving no radiotherapy, 472 receiving EBRT alone, 331 receiving BT alone, and 271 receiving EBRT+BT. On multivariate analysis of the entire analytic cohort, survival was significantly improved among patients receiving EBRT+BT combination (hazard ratio [HR] 0.72, 95% confidence interval [CI] = 0.58–0.89, p < 0.01), but not among those receiving EBRT alone (HR 0.93, 95% CI = 0.79–1.10, p = 0.41) or BT alone (HR 0.84, 95% CI = 0.68–1.03, p = 0.09). These results were confirmed on propensity-score matches for EBRT vs. no RT (HR 0.89, 95% CI = 0.73–1.07, p = 0.34), BT vs. no RT (HR 0.80, 95% CI = 0.63–1.03, p = 0.09), and EBRT+BT vs. no RT (HR 0.74, 95% CI = 0.58–0.96, p = 0.02).ConclusionsEBRT+BT combination is associated with an overall survival advantage in UCS and warrants consideration in the adjuvant management of this disease.     

Prostate gland edema after single-fraction high-dose rate brachytherapy before external beam radiation therapy

PurposeHigh–dose rate brachytherapy (HDRB) is frequently used as a boost to external beam radiation therapy (EBRT) in prostate cancer patients. With the increasing use of small planning target volume margins in EBRT, prostatic edema induced by HDRB can be a contributing factor to geometric miss when HDRB is performed before or during EBRT. We assessed prostate gland volumetric change after single-fraction HDRB and its impact on definition of treatment volume for EBRT.Methods and MaterialsThirty-one consecutive patients with intermediate-risk prostate cancer treated with single-fraction HDRB (10 Gy) combined with hypofractionated EBRT were analyzed. A second CT scan was performed 7 days after HDRB, and images were coregistered with the planning CT scan that contained the original clinical target volume (CTV). The post-HDRB prostate CTV volume was compared with the original CTV by a single observer.ResultsAll patients presented volumetric variation. In most cases (68%), the prostate increased in volume, whereas it decreased in 32%. The mean prostatic volume was 42.2 cc before HDRB and 43.6 cc after HDRB, representing a mean volume difference of 3.4%, ranging from ?14.2% to 23.8% (p = 0.756). This difference is the result of mean changes of 0.6 mm (?6.1 to 6.6) in the anterior–posterior, 0.5 mm (?5.5 to 3.0) in the lateral, and 0.2 mm (?5.0 to 5.0) in the superior–inferior axes.ConclusionsAlthough a nonsignificant volumetric change occurs after single-fraction HDRB, individual variations on specific axis could lead to important uncertainties during EBRT.     

Factors associated with late local failure and its influence on survival in men undergoing prostate brachytherapy

BACKGROUND AND PURPOSETo determine the factors associated with a positive post-treatment prostate biopsy (PB) and the effects of local failure on biochemical control and cause-specific survival (CSS) in men receiving prostate brachytherapy.METHODS AND MATERIALSOf 545 men with post-implant PB, 484 were routine (median 24 months) while 61 (median 55 months) were for cause. 114 had a repeat PB for rising PSA. Initial mean PSA was 10.5 ng/ml (±13.9) while 244 (44.8%), 202 (37.1%) and 99 (18.2%) had low, intermediate or high-risk disease. Treatments were implant only in 287 (52.7%), and implant with androgen deprivation therapy (ADT) ± external beam in 258. Radiation doses were converted to the biologically equivalent dose (BED). Final biopsy results were the last biopsy performed on that patient. Associations for the first and final biopsies with PSA, clinical stage (CS), Gleason grade group, time on hormone therapy (ADT) and BED were determined by ANOVA, chi-square and binary linear regression. Freedom from Phoenix failure (FFPF) and cause-specific survival were estimated by Kaplan Meier method and Cox proportions hazards.RESULTSAfter a median of 11.4 years the first and final biopsy were positive in 10.8% and 8.8%, respectively. Significant linear regression associations with first positive PB were ADT (p = 0.005), CS (p = 0.044) and BED (p = 0.030) while only BED (p < 0.001) was significant for the final PB. Positive biopsy occurred in 21/112 (18.8%), 16/230 (7.0%) and 3/182 (1.6%) for BED ≤150, >150–200 and >200 Gy (p < 0.001), and in 29/261 (11.1%) for BED (median) ≤185 Gy vs. 5/263 (1.9%) for > 185 Gy (OR 4.2, p < 0.001). 15-year FFPF was 75.6 vs. 17.5% and cause-specific survival was 94.2 vs. 75.5% for negative vs. positive biopsy.CONCLUSIONSHigher radiation doses are associated with 1.9% late local failure following prostate brachytherapy. A negative post-implant PB is associated with superior FFPF and decreased prostate cancer mortality.