Definitions Of Biochemical Failure Research Articles

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old-Updated Results.

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports updated outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients. Between April 2006 and December 2022, 6,130 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator. Information was available for 4,143 patients. 3568 (86.12%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 575 (13.88%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 1,035 (24.98%) of these cases. The mean age was 67.4 years old. 48 patients were younger than 50 years old (mean age 46.6). 4,095 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 43.75%, 50.00%, 6.25% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 23.88%, 57.05%, 19.07% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 47.92%, 7 in 47.92%, and 8-10 in 4.16%. 44 younger patients were treated with SBRT alone. 4 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.42%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 29.84%, 7 in 54.14%, and 8-10 in 16.02%. 3522 were treated with SBRT alone. 573 patients also received supplemental external beam radiation (median dose 4500cGY) and 1030 patients (25.15%) received Androgen Deprivation Therapy (ADT) as part of their treatment. At 75 months the 6-year biochemical relapse free survival was 95.83% in younger patients compared to 98.41% in older patients using the Phoenix definition of biochemical failure. The 6-year median post treatment PSA was 0.3 in younger patients and 0.2 in the older patients. There were no significant differences in the risk stratification between the 2 groups. This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With updated 6-year follow up, SBRT remains an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy

AimsTo report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. Materials and methodsIn 2003–2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan–Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. ResultsOf 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3–7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. ConclusionIn low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.

Comparison of AUA and phoenix definitions of biochemical failure following permanent brachytherapy for prostate cancer

To compare biochemical recurrence free survival (BCRFS) and cancer-specific survival (CSS) after brachytherapy using the AUA and the Phoenix definitions. 2634 men with T1-T4N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant hormonal therapy or external beam radiation therapy. Five, 10, and 15- year BCRFS and CSS were estimated with Kaplan-Meier estimates with log rank. Multivariate analysis of survival was performed with Cox regression analysis. Median age was 66, follow-up was 8.6 years, and prostate specific antigen was 6.9. Overall, 11.1% (n = 293) of patients experienced Phoenix BCR and 17.48% (n = 457) experienced AUA BCR. The rates of AUA BCR and Phoenix BCR were significantly different at 5 and 10-years but not at 15 years. Patients treated with BED ≤ 200 Gy were more likely to experience AUA BCR (22.5% vs. 12.4%, OR 1.44, p < 0.001) and Phoenix BCR (14.3% and 8.3%, OR 1.37, p < 0.001) than patients treated with a BED > 200 Gy. Compared to the Phoenix definition, the AUA definition of BCR after brachytherapy is associated with significantly worse BCRFS for the first 15 years after treatment. Receiving a BED > 200, which cannot be achieved without the addition of brachytherapy, is associated with better BCRFS and CSS. Our findings reaffirm the importance of dose in the management of prostate cancer.

Refining the definition of biochemical failure in the era of stereotactic body radiation therapy for prostate cancer: The Phoenix definition and beyond

Background and purposeThe Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs. Materials and methodsPSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSA18month/PSA6month) and timing of reaching nPSA + 2 with BCF. ResultsMedian follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p < 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p < 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%. ConclusionThe Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).

Working Towards a New Definition of Biochemical Failure in the Era of Stereotactic Body Radiation Therapy for Prostate Cancer

Since the seminal Phoenix definition (nadir PSA+2) of biochemical failure (BCF) was published in 2006, increasingly more patients with low- and intermediate-risk prostate cancer (PCa) are being treated with stereotactic body radiation therapy (SBRT). Since SBRT leads to lower nadir PSA (nPSA) compared to conventionally fractionated RT, we investigated if an earlier nPSA+threshold can be used as an alternative definition of BCF.PSA kinetics from 9 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2003 to 2018. Patients received 35 to 40 Gy in 5 fractions, 38 Gy in 4 fractions or 26 Gy in 2 fractions (EQD23 Gy = 70-95 Gy) per institutional standards. Cox multivariable regression model was used to determine the adjusted association of relative change in PSA kinetics with biochemical relapse-free survival (BRFS) and association of BCF with time to nadir+2.A total of 2061 patients were included. Median follow-up was 71.9 months (interquartile range [IQR], 41.2-96.0). BCF occurred in 140 (6.8%) of patients. Median nPSA was 0.16 ng/mL, median time to nPSA was 48 months. Sensitivity of Phoenix definition for BCF was 93%, compared to 96%, 100%, and 100% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. False positive rate of Phoenix definition was 30%, compared to 41%, 58%, and 71% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. In patients who developed BCF, lead time gained from an earlier nPSA+threshold definition compared to Phoenix definition was 6 (IQR 0-15.3), 0 (IQR 0-11.3), 0 (IQR 0-0) months for nPSA+0.5, nPSA+1.0 and nPSA+1.5, respectively. Relative change in PSA between 6 months and 18 months after treatment was significantly associated with BRFS (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.28-2.34, P < 0.0004). Among the 30% patients who had a false call of BCF due to PSA bounce, 48 (84.2%) reached nPSA+2 in ≤18 months, and 9 (15.8%) in > 18 months. In patients who had BCF, 27 (19.3%) reached nPSA+2 in ≤18 months, and 113 (80.7%) in > 18 months. Median time to nPSA+2 was significantly longer in patients with BCF (41 vs. 12 months, P < 0.002). BCF is associated with longer time to nPSA+2 (HR 0.13, 95% CI 0.09-0.20, P < 0.002).A lower nadir-based threshold provides minimal increase in sensitivity at the cost of a higher false positive rate and does not provide a clinically relevant lead time benefit for a pending BCF in patients with low- to intermediate-risk PCa undergoing SBRT. A rate-of-change based metric in the first 18 months post-SBRT is significantly associated with BRFS. Patients who have an early PSA bounce after SBRT rarely develop a true BCF and true BCF tends to happen later (> 18 months). Phoenix definition remains a valuable tool in the SBRT era. BCF should not be prematurely called which runs the risk of high rates of false positivity.

Robotic SBRT in Prostate Cancer Patients Younger Than 50 Years Old

Stereotactic Body Radiation Therapy (SBRT) is a standard therapeutic option for men with prostate adenocarcinoma. The median age of prostate cancer in the US is 66 but patients as young as 35 have been reported. Many younger patients will have surgery rather than SBRT for localized prostate cancer but some will be treated with SBRT. There is a paucity of data on the outcomes of this younger subset. This study reports outcomes on patients younger than 50 treated with SBRT at a single institution and compares outcomes to older patients.Between April 2006 and December 2020, 3626 patients with prostate cancer were treated with inhomogeneous-dosed SBRT using a robotic linear accelerator and followed at an academic institution. 3173 (87.51%) of patients were treated with a median dose of 3500cGY (3500-3625) delivered over 5 consecutive fractions prescribed to the 83-85% isodose line, and the remaining 453 (12.49%) other patients receiving a median dose of 4500cGY (4500-5400) to the pelvis in conventional fractionation followed by a 3 fraction SBRT boost of 2100 cGY (1950-2100) over 3 consecutive fractions. Androgen deprivation Therapy (ADT) was prescribed in 865 (23.86%) of these cases. The mean age was 67.3 years old. 47 patients were younger than 50 years old (mean age 46.6). 3,579 patients were 50 or older. Patients were divided into prognostic D'Amico risk groups with 44.68%, 48.94%, 6.38% of patients falling in the low, intermediate, and high-risk stratifications in the younger cohort and 24.76%, 56.83%, 18.41% in the older cohort respectively. Pretreatment PSA was 1.72 - 43.2 (median: 5.4) in the younger group and 0.3 - 661 (median: 6.5) in the older group. In the younger group, Gleason scores were 6 in 48.94%, 7 in 46.81%, and 8-10 in 4.25%. 44 younger patients were treated with SBRT alone. 3 patients also received supplemental external beam radiation (median dose 4500cGY) and 5 patients (10.6%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen. In the older group, Gleason scores were 6 in 30.57%, 7 in 54.06%, and 8-10 in 15.37%. 3129 were treated with SBRT alone. 450 patients also received supplemental external beam radiation (median dose 4500cGY) and 860 patients (24.03%) received Androgen Deprivation Therapy (ADT) as part of their treatment regimen.At 64.8 months (range 7 months - 177 months) the 5-year biochemical relapse free survival was 98% in younger patients compared to 99% in older patients using the Phoenix definition of biochemical failure. The 5-year median post treatment PSA was 0.15 in the younger patients and 0.20 in the older patients. There were no significant differences in biochemical relapse free survival between the groups.This represents the largest series evaluating outcomes in very young patients treated with definitive SBRT for prostate cancer. With 5-year follow up, SBRT is an effective treatment for this younger subset of patients. Continued follow up will be required to see if these results remain durable.

Is The Phoenix Criterion Of Biochemical Failure (BF) In Men Treated With Low-Dose Rate Prostate Brachytherapy Appropriate?

PSA kinetics post-brachytherapy are not well described. Our aim was to validate the Phoenix criterion (PC nadir+2) for BF in men treated with prostate brachytherapy without ADT, a definition initially established based on retrospective analysis of external beam radiotherapy data. Our dataset consisted of 9,219 patients from 3 countries who received l-125 or Pd-103 low dose rate prostate brachytherapy without ADT. First, to compare the performance of the different PC definitions, we applied ROC analysis to test the significance of the difference between AUC for PC nadir+2 and that for alternative PSA failure definitions (PSA> = X after Y years of follow up, where X = 1.5-4.0 and Y = 0-1.5). Second, the Mann-Whitney rank-sum test was applied to test for any difference between the time to PC nadir+2 failure or time to alternative PSA failure definition, and time to clinical failure in cases where both a clinical failure and a PSA-predicted failure occurred. 4,169 (45.2%), 4,665 (50.6%), and 385 (4.2%) of the patients without ADT were respectively low risk, intermediate risk, and high risk. Median follow up was 5.3 years. Alternative definitions of BF were not significantly superior to the PC nadir+2 (all p-values > 0.05). The times to clinical failure after biochemical failure were slightly but not significantly shorter for the PC nadir+2 definition (1.6 y) than for those using the best-performing of the alternative definitions: PSA> = 3 after 0.5 years follow up (1.84 y). Findings from an international cohort validate use of the nadir+2 PC for BF in men receiving definitive low dose rate prostate brachytherapy without androgen deprivation therapy for prostate cancer.

MP53-20 PREDICTING SURVIVAL OUTCOMES AFTER BRACHYTHERAPY USING THE AUA AND PHOENIX DEFINITION OF BIOCHEMICAL FAILURE

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (MP53)1 Apr 2020MP53-20 PREDICTING SURVIVAL OUTCOMES AFTER BRACHYTHERAPY USING THE AUA AND PHOENIX DEFINITION OF BIOCHEMICAL FAILURE Zeynep G. Gul*, Rollin K. Say, Shirin Razdan, and Nelson N. Stone Zeynep G. Gul*Zeynep G. Gul* More articles by this author , Rollin K. SayRollin K. Say More articles by this author , Shirin RazdanShirin Razdan More articles by this author , and Nelson N. StoneNelson N. Stone More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000915.020AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Biochemical failure (BF) after radiation therapy is defined by the Phoenix definition as the nadir PSA +2. After radical prostatectomy, the AUA definition of BF is a PSA >0.2. The objective of the current study was to compare the AUA and Phoenix definitions of BF as predictors of distant metastasis (DM) and overall survival (OS). METHODS: 2319 men with T1-T4N0M0 prostate cancer were treated with brachytherapy. The mean follow-up was 105 months (8.75 years) and the mean biological effective dose (BED) was 195. Cox regression analysis were performed to determine the associations of AUA BF and Phoenix BF on DM and OS. The other variables included in the analysis were total BED, initial PSA, age at diagnosis, Gleason Score (6 vs 7-10), and clinical stage (T1/T2 vs T3/T4). RESULTS: BF occurred in 413 (17.8%) and 260 (11.2%) men according to the AUA and Phoenix definition, respectively. DM were seen in 71 patients (3.1%). 449 men (19.4%) died during follow up and 65 (2.8%) died from prostate cancer. Both the AUA and Phoenix definitions were significantly associated with DM and OS. CONCLUSIONS: The AUA and Phoenix definitions of BF are similar in their ability to predict DM and OS. Using the AUA definition would allow for better comparisons of outcomes following radical prostatectomy and brachytherapy. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e790-e790 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zeynep G. Gul* More articles by this author Rollin K. Say More articles by this author Shirin Razdan More articles by this author Nelson N. Stone More articles by this author Expand All Advertisement PDF downloadLoading ...

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

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

Comparison of outcome endpoints in intermediate- and high-risk prostate cancer after combined-modality radiotherapy

PurposeTo compare a standard radio-oncological and a surgical biochemical failure definition after combined-modality radiation therapy (CRT) in men with intermediate- and high-risk prostate cancer. Methods425 men were treated with external beam radiotherapy (59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Biochemical recurrence (BR) was defined either as radio-oncologic (rBR), using a +2 ng/mL prostate-specific antigen (PSA) increase above a nadir value, or as surgical (sBR), using a 2-year posttreatment PSA of ≥0.2 ng/mL. Biochemical recurrence-free, metastasis-free, cancer-specific, and overall survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard validation tests were used to compare both thresholds. ResultsAfter a median of 7 years, overall recurrence rates were 10.4% and 31.5% for rBR and sBR definitions, respectively. Both failure definitions proved sensitive for the prediction of metastases and cancer-specific death, whereas the rBR definition was significantly more specific. The accuracies of a correct prediction of metastases and death of prostate cancer were 73.1% vs. 96.2% and 72.2% vs. 92.9% for sBR vs. rBR, respectively. The inferior validity results of the sBR definition were attributable to a PSA-bounce phenomenon occurring in 56% of patients with sBR. Still, using the less suitable sBR definition, the results of CRT compared favorably to BRFS rates of surgical interventions. ConclusionAfter CRT, the radio-oncological (aka Phoenix) failure definition is more reliable than a fixed surgical endpoint. Exclusively in high-risk patients, sBR offers a direct comparison across surgical and nonsurgical treatment options at 5 and 10 years.

111 Robustness of the Phoenix Biochemical Failure Definition 10 Years After Completing Dose Escalated Radiotherapy in a Cohort of Intermediate Risk Prostate Cancer Patients

111 Robustness of the Phoenix Biochemical Failure Definition 10 Years After Completing Dose Escalated Radiotherapy in a Cohort of Intermediate Risk Prostate Cancer Patients

Robustness of the Phoenix Biochemical Failure Definition 10 Years after Completing Dose Escalated Radiotherapy in a Cohort of Intermediate Risk Prostate Cancer Patients

Robustness of the Phoenix Biochemical Failure Definition 10 Years after Completing Dose Escalated Radiotherapy in a Cohort of Intermediate Risk Prostate Cancer Patients

Dose escalation (81 Gy) with image-guided radiation therapy and volumetric-modulated arc therapy for localized prostate cancer: A retrospective preliminary result.

Objectives:The objective of the study is to report the acute and late toxicity and preliminary results of localized prostate cancer treated with high-dose radiation therapy (RT).Materials and Methods:Between March 2010 and October 2018, a total of 53 patients with clinically localized prostate cancer were treated with definitive RT at our institution. All patients were planned to receive a total dose of 81 Gy with the volumetric-modulated arc therapy technique. Patients were stratified by prognostic risk groups based on the National Comprehensive Cancer Network risk classification criteria. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. The definition of biochemical failure was using the 2005 ASTRO Phoenix consensus definition. Median follow-up time was 46.5 months (range: 4.7–81.0 months).Results:The 3-year biochemical failure-free survival rates for low-, intermediate-, and high-risk group patients were 100%, 87.5%, and 84%, respectively. The 3- and 5-year overall survival rates were 83% and 62%, respectively. Three (5.6%) patients developed Grade II acute gastrointestinal (GI) toxicity. Four (7.5%) patients developed Grade II acute genitourinary (GU) toxicity, and none experienced Grade III or higher acute GI or GU symptoms. One (1.8%) patient developed Grade II or higher late GI toxicity. Six (11.3%) patients experienced Grade II late GU toxicity. No Grade III or higher late GI and GU complications have been observed.Conclusions:Data from the current study demonstrated the feasibility of dose escalation with image-guided and volumetric-modulated arc therapy techniques for the treatment of localized prostate cancer. Minimal acute and late toxicities were observed from patients in this study. Long-term prostate-specific antigen controls are comparable to previously published results of high-dose intensity-modulated RT for localized prostate cancer. Based on this favorable outcome, dose escalation (81 Gy) has become the standard treatment for localized prostate cancer at our institution.

Radiobiological parameters in a tumour control probability model for prostate cancer LDR brachytherapy

To provide recommendations for the selection of radiobiological parameters for prostate cancer treatment planning. Recommendations were based on validation of the previously published values, parameter estimation and a consideration of their sensitivity within a tumour control probability (TCP) model using clinical outcomes data from low-dose-rate (LDR) brachytherapy.The proposed TCP model incorporated radiosensitivity (α) heterogeneity and a non-uniform distribution of clonogens. The clinical outcomes data included 849 prostate cancer patients treated with LDR brachytherapy at four Australian centres between 1995 and 2012. Phoenix definition of biochemical failure was used. Validation of the published values from four selected literature and parameter estimation was performed with a maximum likelihood estimation method. Each parameter was varied to evaluate the change in calculated TCP to quantify the sensitivity of the model to its radiobiological parameters.Using a previously published parameter set and a total clonogen number of 196 000 provided TCP estimates that best described the patient cohort. Fitting of all parameters with a maximum likelihood estimation was not possible. Variations in prostate TCP ranged from 0.004% to 0.67% per 1% change in each parameter. The largest variation was caused by the log-normal distribution parameters for α (mean, , and standard deviation, σα).Based on the results using the clinical cohort data, we recommend a previously published dataset is used for future application of the TCP model with inclusion of a patient-specific, non-uniform clonogen density distribution which could be derived from multiparametric imaging. The reduction in uncertainties in these parameters will improve the confidence in using biological models for clinical radiotherapy planning.

Can post-operative prostate fossa radiation be omitted in patients with high-risk features using a genomic classifier?

101 Background: At our institution, based upon the AUA/ASTRO guidelines, discussion of adjuvant radiation therapy (ART) for patients with adverse pathologic features (APF) (pT3/positive margins) occurs in a multidisciplinary setting. We had previously offered ART to approximately 50% of these patients. We describe our evaluation of Decipher genomic testing to select patients to offer observation following prostatectomy (RP). Methods: Since March 2014, patients at Thomas Jefferson University with APF and undetectable post-operative PSA underwent Decipher genomic testing. Collectively, we decided to offer observation with salvage radiation therapy (SRT) for patients with low or intermediate risk Decipher scores. The primary outcome of this analysis was biochemical progression free survival (bPFS) with failure defined as a PSA ≥0.1 ng/mL. Results: From March of 2014 through September of 2016, 47 patients met the above criteria. The median patient age was 64 and median follow up was 16 months. Median pre-treatment PSA was 6.0 ng/mL (2.94 to 22.7 ng/mL). With regard to pathologic stage: 19% had T2c, 68% had T3a, and 13% had T3b disease. Pathologic Gleason grouping was 6%, 49%, 34%, 6%, and 4% for groups 1-5, respectively. 51% of patients had positive margins, 36% had lymph-vascular space invasion, and 53% had perineural invasion. Four patients received ART and 1 patient was lost to follow up after his initial visit. Of the remaining 42 patients, 3 patients experienced biochemical failure at 8, 27, and 44 months. Conclusions: This is the first prospective report utilizing Decipher genomic testing to stratify men with undetectable PSA and adverse pathologic features into an observation cohort following RP. Despite the stringency of our definition of biochemical failure, our observed bPFS was 87% at 3 years. Historically, in an unselected population the 3 year bPFS was 90% in those receiving ART and 65% in those receiving SRT. While these initial findings are promising, longer follow up is warranted. Our findings demonstrate the utility of genomic classifiers in patient selection and provide a safe approach to reducing over treatment in the post RP setting.

Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer.

To evaluate the feasibility, safety, early quality-of-life (QoL) and oncological outcomes of salvage focal irreversible electroporation (IRE) for radio-recurrent prostate cancer (PCa). Patients with localized, radio-recurrent PCa without evidence of metastatic or nodal disease were offered focal IRE according to the consensus guidelines. Patients with a minimum follow-up of 6months were eligible for analysis. Adverse events were monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Patient-reported QoL data were collected at baseline, 6weeks, 3, 6 and 12months using the Expanded Prostate Cancer Index Composite (EPIC), the American Urological Association (AUA) symptom score and the 12-item short-from health survey (SF-12) physical and mental component summary questionnaires. Oncological control was evaluated according to serial prostate-specific antigen (PSA), 6-month multiparametric magnetic resonance imaging (mpMRI) and 12-month prostate biopsy. Wilcoxon's signed rank test was used to assess QoL differences over time in paired continuous variables. A total of 18 patients were included in the analysis. The median follow-up was 21months. No high-grade adverse events (CTCAE >2) or recto-urethral fistulae occurred. No statistically significant declines were observed in QoL outcomes (n = 11) on the EPIC bowel domain (P = 0.29), AUA symptom score (P = 0.77), or the SF-12 physical (P = 0.17) or SF-12 mental component summary (P = 0.77) questionnaires. At 6months, patients who had undergone salvage therapy experienced a decline in EPIC sexual domain score (median of 38-24; P = 0.028) and urinary domain (median of 96-92; P = 0.074). Pad-free continence and erections sufficient for intercourse were preserved in 8/11 patients and 2/6 patients at 6months, respectively. The mpMRI was clear in 11/13 patients, with two single out-field lesions (true-positive and false-positive, respectively). The median (interquartile range) nadir PSA was 0.39 (0.04-0.43)μg/L. Three and four patients experienced biochemical failure using the Phoenix and Stuttgart definitions of biochemical failure, respectively. Eight out of 10 of the patients were clear of any PCa on follow-up biopsy, whereas two patients had significant PCa on follow-up biopsy (International Society of Urological Pathology grade 5). Our short-term safety, QoL and oncological control data show that focal IRE is a feasible salvage option for localized radio-recurrent PCa. A prospective multicentre study (FIRE trial) has been initiated that will provide further insight into the ability of focal IRE to obtain oncological control of radio-recurrent PCa with acceptable patient morbidity.

Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer

Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size. Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950cGy × 4 fractions, 1200cGy × 2 fractions, 1350cGy × 2 fractions, 1900cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0ng/mL above the prior nadir with a subsequent return to the nadir. The median follow-up period was 3.7years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0ng/mL, respectively. The 3-year rate of PSA bounce >0.2ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2ng/mL for patients receiving a single fraction of 1900cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025). The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.

A combined single high-dose rate brachytherapy boost with hypofractionated external beam radiotherapy results in a high rate of biochemical disease free survival in localised intermediate and high risk prostate cancer patients

IntroductionDose escalation has been shown to improve biochemical outcome in localised prostate cancer. An HDR brachytherapy boost is an effective strategy for dose escalation, since it exploits the low α/β ratio in prostate cancer, allowing the delivery of a high biological dose to the tumour. We sought to evaluate the biochemical disease free survival in patients with intermediate and high risk localised prostate cancer treated with EBRT plus HDR brachytherapy as a boost, in our institution. Patients and methodsBiochemical outcome was collected prospectively in 95 patients treated from 2008 to 2010, with an HDR boost of 12.5Gy followed by EBRT delivered as 37.5Gy in 15 fractions over 3weeks. The ASTRO definition of biochemical failure (2μg/L above PSA nadir) was used as the outcome measure. 61/95 (64%) were classified as high risk (stage>T2b or PSA>20μg/L or Gleason score>7) while 34/95 (36%) were intermediate risk. 92/95 (97%) patients received neoadjuvant androgen deprivation therapy (ADT). Adjuvant hormone therapy was at the discretion of the treating clinician. ResultsThe median follow-up for the cohort was 65months (range, 18–88) with a 5-year biochemical DFS of 80.5% (95% Confidence Interval [CI]: 72.8–89.0). The prognostic factors used in the analysis model were: clinical stage, presenting PSA, duration of ADT, Gleason score, risk category, prostate volume, D90 and V100. Only presenting PSA (HR 1.03; CI 1.00–1.05, p=0.03) predicted for a poorer biochemical DFS on multivariate analysis. ConclusionThese data confirm that EBRT plus a single-fraction HDR brachytherapy boost achieves good biochemical control in a cohort of predominantly high risk patients.

Single session of high-intensity focused ultrasound therapy for the management of organ-confined prostate cancer: A single-institute experience

ObjectiveThe aim of this study was to evaluate the therapeutic response and complications of high-intensity focused ultrasound for patients with localized prostate cancer. Materials and MethodsWe evaluated the clinical outcomes of 29 patients who received high-intensity focused ultrasound as first-line treatment for localized prostate cancer at our hospital from October 2010 to March 2016. Biochemical recurrence was defined, according to the Stuttgart definition of biochemical failure, as the prostate-specific antigen nadir plus 1.2 ng/mL. Prostate-specific antigen levels and complications were recorded during regular follow-up. ResultsThe mean follow-up period was 24.6 months. Six patients experienced biochemical recurrence (20.68%). Disease progression was noted in six patients (20.68%), and salvage therapy was performed in these patients. The 24.6-month cancer-specific survival rate was 100%. No severe complications were reported. ConclusionHigh-intensity focused ultrasound is an alternative therapy for patients with localized prostate cancer. In combination with preceding transurethral resection of the prostate, this treatment shows promise in disease control with a low complication rate in short-term follow-up.

S&T-53 TEN-YEAR OUTCOMES OF TREATMENT FOR LOCALIZED PROSTATE CANCER IN A SINGLE INSTITUTION; COMPARISON OF RADICAL PROSTATECTOMY VS RADIATION THERAPY ~PROPENSITY SCORE MATCHING ANALYSIS~

You have accessJournal of UrologyScience & Technology Posters1 Apr 2016S&T-53 TEN-YEAR OUTCOMES OF TREATMENT FOR LOCALIZED PROSTATE CANCER IN A SINGLE INSTITUTION; COMPARISON OF RADICAL PROSTATECTOMY VS RADIATION THERAPY ~PROPENSITY SCORE MATCHING ANALYSIS~ Narihiko Hayashi, Yumiko Yokomizo, Kimito Osaka, Kazuhikde Makiyama, Noboru Nakaigawa, Masahiro Yao, and Masataka Taguri Narihiko HayashiNarihiko Hayashi More articles by this author , Yumiko YokomizoYumiko Yokomizo More articles by this author , Kimito OsakaKimito Osaka More articles by this author , Kazuhikde MakiyamaKazuhikde Makiyama More articles by this author , Noboru NakaigawaNoboru Nakaigawa More articles by this author , Masahiro YaoMasahiro Yao More articles by this author , and Masataka TaguriMasataka Taguri More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2882AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radical prostatectomy (RP), intensity modulated radiation therapy (IMRT) and brachytherapy (BT) are three major definitive treatment modalities for localized prostate cancer in recent years. While a lot of technical progress are seen in this decade, patients with localized prostate cancer are often struggling with making a decision of their treatment. It might be due to luck of information in terms of comparing the outcomes among these modalities since only few reports are seen in the literature. Propensity score matching analysis in nonrandomized studies is to balance the treatment and comparison groups on observed preintervention characteristics. Though it may not be considered an equivalent to randomized trial, it reduces to a minimum the inherent treatment selection bias associated with retrospective data. We analyzed the results of three treatment modalities in a single institution in Japan. METHODS From Jan 2004 to Aug 2014, a group of 1943 patients with clinically localized prostate cancer treated with RP (454pts), IMRT (343pts) and BT(1146pts) were identified in our institution. The records of RP (n=362), IMRT (n=225) and BT (n=826) patients with a minimum of 2 years of follow-up (total 1413) were reviewed. Propensity scores were calculated using multivariable logistic regression based on the covariates including patient's age, preoperative PSA, Gleason score, number of positive cores, clinical T stage. Each cohort were categorized according to NCCN risk classification and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as RP: PSA >0.2ng/ml, IMRT, BT: nadir PSA level +2ng/ml. RESULTS Median follow-up was 69.1 months (mo) for RP, 51.0 mo for IMRT and 57.3 mo for BT patients. After adjustment of propensity scores, a total of 260 patients (130 each) and 428 patients (214 each) were matched for RP vs IMRT cohort and RP vs BT cohort, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival in these two cohorts (RP vs IMRT:p=0.421, RP vs BT:p=0.764). Regarding biochemical failure free survival, there was statistically significant differences in all risk group in RP vs IMRT cohort (High-risk: p=0.000, Intermediate-risk: p=0.001, Low-risk: p=0.007), while significant differences were observed in low (p=0.003), intermediate (p=0.006) risk group among RP vs BT cohort. CONCLUSIONS Our mid-term outcomes for localized prostate cancer using propensity score analysis demonstrated no significant differences in overall survival. Despite the difference of biochemical failure definition, IMRT and BT improved biochemical failure free survival compared to RP with excellent tumor control in Japanese people © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e330 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Narihiko Hayashi More articles by this author Yumiko Yokomizo More articles by this author Kimito Osaka More articles by this author Kazuhikde Makiyama More articles by this author Noboru Nakaigawa More articles by this author Masahiro Yao More articles by this author Masataka Taguri More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...