bNED Rates Research Articles

Comparative evaluation of hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate and high risk prostate cancer.

The purpose of this study was to comparatively evaluate an efficacy and toxicity profile of hypofractionated radiotherapy (67.5 Gy in 25 fractions) to conventionally fractionated radiotherapy (78 Gy in 39 fractions) in prostate cancer patients with intermediate and high-risk disease. From January 2015 to December 2018, 168 patients were randomized to hypofractionated radiation treatment and conventional fractionated radiation treatment schedules of volumetric modulated arc therapy (VMAT) to the prostate and seminal vesicles. All the patients also received androgen deprivation therapy (ADT) and radiation therapy started after ADT. The median (range) follow-up was 51 (31-63) and 53 (33-64) months in the hypofractionated and conventionally fractionated regimes, respectively. The 3-year biochemical no evidence of disease (bNED) rates were 86.9% and 73.8% in the hypofractionated and conventionally fractionated groups, respectively (p = 0.032, significant). The 3-year bNED rates in patients at a high risk [i.e., pretreatment prostate-specific antigen (PSA) > 20 ng/mL, Gleason score ≥ 8, or T ≥ 2 c], were 87.9% and 73.5% (p = 0.007, significant) in the hypofractionated and conventionally fractionated radiotherapy groups, respectively. No statistically significant difference was found for late toxicity between the two groups, with 3-year grade 2 gastrointestinal toxicity rates of 19% and 16.7% and 3-year grade 2 genitourinary toxicity rates of 15.5% and 11.9% in the hypofractionated and conventionally fractionated radiotherapy groups, respectively. Hypofractionated schedule is superior to the conventional fractionation schedule of radiation treatment in terms of bNED in intermediate and high grade prostate cancer patients. Also, the late toxicity is found to be equivalent between the two treatment groups.

The Prognostic Value of the Size and the Sub-Site of the Local Failure at DCE-MRI before Salvage Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> To investigate predictors of biochemical failure after salvage radiotherapy (sRT) in the context of a presumed local failure at dynamic contrast-enhancement-magnetic resonance imaging (DCE-MRI) post radical prostatectomy (RP). <h3>Materials/Methods</h3> All patients referred for sRT at our Institution with a biochemical failure after RP have been consistently offered restaging with both PET/CT and multiparametric MRI since January 2014. Those with a presumed local failure at DCE-MRI as well as no regional/distant disease at PET/CT (either choline and/or PSMA) were selected for the present study. Exclusion criteria were history of androgen deprivation (AD) before sRT and positive nodes at RP. All patients underwent 3T DCE-MRI without endorectal coil and the lesion(s) transferred to the planning CT after co-registration. sRT consisted in 73.5 Gy to the presumed local lesion and 66-69 Gy to the prostatic bed in 30 fxs. Pelvic nodes (PN) were covered to 54 Gy/30 fxs in selected patients. The endpoint of the study was the development of a biochemical failure after sRT defined as a 0.2 ng/ml PSA rise above the nadir. Various covariates (age, pre-RP PSA, pT and pN stages at RP, margins status at RP, ISUP grade group, time from RP to sRT, PSA doubling time, PSA detectability after RP, PSA at sRT, the location, number and volume of the detected recurrence(s), AD use, PN coverage, EUA risk category) were investigated at univariate analysis (UVA) on the time to biochemical failure (bNED-survival). Covariates with a p value <0.2 at UVA were entered a Cox proportional hazards regression analysis. <h3>Results</h3> Up to June 2020, 146 patients satisfying all selection criteria have been treated with sRT. Median (IQR) PSA at sRT was 0.60 ng/ml (0.38-1.05 ng/ml) and only 17 patients (11.6%) received AD along with sRT. A total of 168 local lesions have been detected, 92 (54.8%), 40 (23.8%) and 36 (21.4%) at the vesicourethral anastomosis (VUA), the bladder neck and the retrovesical space, respectively. At the median (IQR) follow-up of 48.1 months (31.3-60.6 months), 22 biochemical failures have been observed for a 4-yr bNED survival of 84.4% (95%CI: 77.9-90.9%). On UVA, bNED-survival after sRT was significantly more likely for patients with VUA-only lesions (VUA-only vs others, HR=0.307, 95%CI: 0.120-0.784, p=0.014) and with smaller lesions (for every cc, HR: 1.071, 95%CI: 1.025-1.119, p=0.002). These associations remained significant (p< 0.01) on multivariate analysis as well. For patients with VUA-only disease or with lesions smaller than 0.5cc, 4-yr bNED survival rates were 90.7% (95%CI: 83.4-98.0%) and 90.6% (95%CI: 83.9-97.3%), respectively. The 46 patients with both favorable features had a 4-yr bNED rate of 94.6% (95%CI: 87.3-100%). <h3>Conclusion</h3> These data support local restaging with DCE-MRI before sRT in the setting of a biochemical failure after RP. Patients with VUA-only and/or small volume lesions have an excellent outcome after dose-escalated sRT.

Advancements in the radiooncological treatment of high-risk prostate cancer: a quarter century of achievements.

BackgroundThe aim of the study was to evaluate the development of treatment of primary high-risk prostate cancer in regards to biochemical no evidence of disease (bNED), acute and late gastrointestinal (GI) and genitourinary (GU) side effects.Patients and methodsPrimary high-risk prostate cancer patients treated between 1994 and 2016 were included. Applied doses ranged from 60 to 80 Gy, with a dose of 1.8 or 2 Gy per fraction. Techniques were either 3D conformal or intensity modulated radiotherapy and volumetric intensity modulated arc therapy.Results142 patients were treated with doses up to 70 Gy (median dose 66 Gy; 66 Gy group), 282 with doses between 70 and 76 Gy (median dose 74 Gy; 74 Gy group), and 141 with doses >76 Gy (median dose 78 Gy; 78 Gy group). The median follow-up was 48 months. The bNED rates were 50% after 5 years and 44% after 9 years in the 66 Gy group; 65% and 54%, respectively, in the 74 Gy group; and 83% and 66%, respectively, in the 78 Gy group (p = 0.03 vs. 74 Gy and p < 0.0001 vs. 66 Gy). We found a higher rate of acute GI side effects in the 78 Gy group compared to the other groups, but not in maximum acute GU side effects and late maximum GI and GU effects.ConclusionsHigh-risk prostate cancer patients treated with doses of 78 Gy had significantly better bNED rates. Compared to the historical 66 Gy group, 50% more patients achieved bNED after a follow-up of 9 years.

A Prospective Trial of Aggressive Therapy Consisting of Neoadjuvant Chemotherapy and Androgen Deprivation Followed by Prostatectomy and Adjuvant Radiation in High/Very High-Risk Prostate Cancer

Prostatectomy (RP) is a treatment (tx) option even for high-risk prostate cancer (PC) per the NCCN guidelines. We report the long-term follow-up of a pilot clinical trial using an aggressive multimodal approach integrating chemo-hormone tx, prostatectomy (RP) and adjuvant radiation (RT) in men with high/very high-risk PC.Preoperative tx entailed 6 months (mo) of chemo-hormones consisting of LHRH agonist (6 mo) integrated with adriamycin (A) and docetaxel (T). Two dose levels of A and T were incorporated with LHRH agonist tx: a higher dose (HD) of A (50mg/m2) and T (70mg/m2), and a lower dose (LD) of A (15mg/m2) and T (30mg/m2). HD chemo was given on 2 separate occasions (3 days post LHRH injection) in an effort to take advantage of the expected testosterone surge that occurs 3-5 days post LHRH agonist tx, while LD chemotherapy was given at other time points during the 6-month neoadjuvant period. This was followed by RP. The median post-op RT dose was 70.2 Gy (whole pelvis, with cone downs; range: 64.8-70.2) via 3D-CRT/IMRT. Three patients did not undergo RP after neoadjuvant chemo-hormone tx and went on to receive definitive RT (75.6 Gy). The overall survival (OS), disease-free survival (DFS), freedom from PSA failure (bNED, PSA > 0.2), and late GI/GU toxicity rates were calculated using the Kaplan-Meier method.A total of 22 men were enrolled from 2002-2006. Median pre-tx age, PSA and Gleason score were 61 years (range, 43-70), 24.1 ng/ml (range, 1.6-168.3) and 7 (range, 6-10), respectively. A total of 77% of patients received all therapy as planned. Median follow-up for the entire cohort and those alive were 10.9 years (range, 3.4-18.4) and 16.8 years (range, 15-18.4), respectively. The 15-year OS, DFS and bNED rates were 31.2%, 22.7% and 46.2%, respectively. Six patients (27%) never achieved PSA < 0.2. Worst acute grade 3 and 4 toxicity rates were 68% and 32%, respectively. The 15-year actuarial grade 3 or worse late GU toxicity rate was 13%. There was no grade 3 or worse late GI toxicities and no grade 5 acute or late toxicity.Despite an aggressive multimodal regimen that incorporated chemo-hormones, RP and adjuvant RT for high/very high-risk prostate cancer, the 15-year bNED rate was only 46.5%. Therefore, the role of RP and neoadjuvant chemo-hormone therapy remains questionable among high-risk patients in light of superior long-term outcomes demonstrated in trials like ASCENDE-RT that incorporated brachytherapy boost with RT and androgen deprivation.

Comparison of EBRT and I-125 seed brachytherapy concerning outcome in intermediate-risk prostate cancer

PurposeThis study’s objective was the comparison of external beam radiotherapy (EBRT) and I‑125 seed brachytherapy regarding clinical outcome and development of side effects.Patients and methodsIn all, 462 localized intermediate-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seed brachytherapy or EBRT with a dose of 74 or 78 Gy were included: 297 patients were treated with EBRT and 165 with seeds. Biochemical no evidence of disease (bNED) rates according to Phoenix definition as well as late gastrointestinal and urogenital side effects (EORTC/RTOG) were assessed.ResultsPatients were followed up yearly with a median follow-up of 54 (3–192) months. Observed bNED rates for 74 Gy, 78 Gy and seeds were 87, 92, and 88% after 5 years and 71, 85, and 76% after 9 years, respectively. No significant differences were found comparing seeds with 74 Gy (p = 0.81) and 78 Gy (p = 0.19), as well as between 74 and 78 Gy (p = 0.32). Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥ 2 toxicity compared to seeds, but at no point of the follow-up more than 10% of all patients. However, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 33% RTOG grade ≥ 2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time.ConclusionFavorable intermediate-risk prostate cancer patients can be treated either by external beam radiotherapy (74/78 Gy) or permanent interstitial seed brachytherapy.

Biochemical control after adjuvant radiation therapy for prostate cancer: a\xa0unicentric, retrospective analysis

PurposeTo retrospectively evaluate the biochemical no evidence of disease (bNED) and late side effects after adjuvant radiotherapy in prostate cancer patients.MethodsPatients (n = 85) treated with external beam radiotherapy between 1997 and 2013 following radical prostatectomy (RPE) with pathological tumour stage pT2c with positive surgical margins or pT3 and pT4 tumours with or without positive margins who presented with a postoperative and a preradiation prostate-specific antigen (PSA) level below 0.1 ng/ml. The mean dose applied was 66 Gy with conventional fractionation (4 field box-technique). No androgen deprivation therapy was administered, and patients with incomplete data (missing Gleason score, pT stage, or PSA values postoperatively and/or prior to radiation at the presentation at our department) have been excluded from the analysis. Biochemical recurrence was defined as reaching a PSA level > 0.2 ng/ml during follow-up and bNED rates were assessed. In addition, patients were divided into two groups according to the Roach formula for predicting the risk of pelvic node involvement at a cut-off value of 15%. Late urogenital and gastrointestinal side effects (EORTC/RTOG) were assessed.ResultsAfter a median follow-up of 60 months the bNED rate was 88% at 5 years and 72% at 10 years for all patients. Patients with low risk of lymph node involvement (group < 15%) had a 5 year and 10 year bNED of 97% and 85%, while patients with high risk of positive lymph node involvement (group > 15%) showed corresponding bNED rates of 77% and 52%, respectively. A significant difference according to the Roach stratification was detected (p ≤ 0.002). Late urogenital (UG) and gastrointestinal (GI) grade ≥ 2 side effects were detected in 10% and 15%, respectively.ConclusionPostoperative radiotherapy with an average dose of 66 Gy to the prostatic fossa following RPE provides excellent tumour control rates with acceptable side effects. Patients with a higher risk of positive lymph nodes (> 15%) according to the Roach formula show significant worse tumour control rates.

Treatment of low-risk prostate cancer: a\xa0retrospective study with 477\xa0patients comparing external beam radiotherapy and I-125 seeds brachytherapy in terms of biochemical control and late side effects

PurposeThe goal of our study was comparison of external beam radiotherapy (EBRT) and I‑125 seeds brachytherapy in terms of biochemical control and development of late gastrointestinal and genitourinary side effects.Patients and methods477 low-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seeds brachytherapy or EBRT with a dose of 74 or 78 Gy were reviewed for our analysis. 213 patients were treated with EBRT and 264 with seeds.ResultsPatients were followed up yearly with a median follow-up of 70 (3–192) months. The biochemical no evidence of disease (bNED) rates after 5 years were 95% for both EBRT and seeds, and after 10 years 87% for EBRT and 94% for seeds using the Phoenix criteria, although no significant difference was observed. Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥2 toxicity compared to seeds, but at no point in follow-up more than 15% of all patients. On the other hand, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 40% RTOG grade ≥2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time.ConclusionBoth EBRT and seeds provide excellent biochemical control with bNED rates after 10 years of about 90%. In terms of side effects, patients treated with seeds show higher grades of genitourinary side effects, while patients treated with EBRT show higher grades of gastrointestinal side effects.

High–intermediate prostate cancer treated with low-dose-rate brachytherapy with or without androgen deprivation therapy

PurposeTo describe outcomes of men with unfavorable (high-tier) intermediate risk prostate cancer (H-IR) treated with low-dose-rate (LDR) brachytherapy, with or without 6 months of androgen deprivation therapy (ADT). Methods and MaterialsPatients with H-IR prostate cancer, treated before 2012 with LDR brachytherapy without external radiation are included. Baseline tumor characteristics are described. Outcomes between groups receiving ADT are measured by Phoenix (nadir +2 ng/mL), and threshold 0.4 ng/mL biochemical relapse definitions (bNEDs), as well as clinical end points. Standard descriptive and actuarial statistics are used. ResultsTwo hundred sixty men were eligible, 139 (53%) did not receive ADT and 121 (47%) did. Median follow-up was 5 years. Men treated with ADT had higher T stage and percent positive cores but lower pathologic grade group. bNED rates with and without ADT at 5 years are 86% and 85% (p = 0.52) with the Phoenix definition, and 83% and 78% (p = 0.13) with the threshold definition. Local recurrence or metastasis were rare in both groups (<5%, p = not significant). Death from prostate cancer only occurred in 4 patients, 2 in each group. Overall survival was 85% in those treated with ADT and 93% without at 8 years, p = 0.15. ConclusionsThe addition of 6 months of ADT to LDR brachytherapy for H-IR prostate cancer does not improve 5 year prostate specific antigen control, and we no longer routinely recommended it.

The 5-Year Outcomes of Moderately Hypofractionated Radiation Therapy for Localized Prostate Cancer

Reports of a lower alpha-beta ratio of prostate cancer than that of surrounding normal tissues suggested that hypofractionated radiotherapy using fewer and larger fractional doses could be more effective than conventional radiotherapy. The aim of this study is to evaluate therapeutic outcomes and toxicities of hypofractionated radiotherapy for localized prostate cancer. This is retrospective review of 195 patients with localized prostate cancer who underwent intensity-modulated radiotherapy consisting of 66 Gy delivered in fractions of 3 Gy every other weekday between May 2005 and December 2011. The proportion of risk classifications according to D’Amico classifications, low-risk was 27 patients (13.8%), intermediate-risk was 70 patients (35.9%), and high-risk was 98 patients (50.3%). Patients received androgen deprivation therapy according to our institutional criteria based on perceived low-, intermediate-, or high-risk of their diseases. Biochemical failure was defined as prostate-specific antigen nadir plus 2.0 ng/mL. As for toxicities, the patient-reported outcomes (PROs) were assessed using the expanded prostate cancer index composite at six points such as before radiotherapy (baseline), and 1 month, 3 months, 6 months, 12 months and 24 months after radiotherapy. In addition, the clinician-reported outcomes were assessed based on the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Toxicity criteria. Over a median follow-up of 69 months (range, 9 to 138 months), 13 of 195 patients experienced biochemical failure within a median of 40 months (range, 14 to 95 months). The 5-year overall survival rate was 97.7%, and the 5-year no biological evidence of disease rate was 95.0%. By the risk classifications, the 5-year bNED rates were 100%, 96.3% and 90.6% for those with low-, intermediate- and high-risk diseases, respectively. PROs showed that there was a significant difference among the average values of the general urinary and bowel domains. The average score of these domains significantly decreased at 1 month after completion of radiotherapy, and then returned to the baseline level at 3 months after radiotherapy. Acute genitourinary (GU) toxicities were graded 0-1 in 168 patients and two in 27 patients; none was graded three or higher. Late GU toxicities were graded 0-1 in 190 patients and two in 5 patients; none was graded three or higher. Gastrointestinal (GI) toxicities were graded 0-1 in 193 patients and two in 2 patients; none was graded three or higher. Using of this protocol of moderately hypofractionated radiotherapy (a total dose of 66 Gy/22 fraction for 7 weeks) yielded satisfactory clinical outcomes with significant reduction of toxicity profiles including PROs, although follow-up period is not long enough to allow a definitive conclusion.

Long-term results of a prospective phase II study of androgen deprivation therapy, external radiation, cs-131 brachytherapy, and adjuvant docetaxel in high-risk prostate cancer.

5079 Background: We report the long-term results of a prospective, Phase II study of 2 years androgen deprivation therapy (ADT), 45 Gy bone marrow sparing pelvic radiation (BMS-PR), Cs-131 brachytherapy boost (85 Gy), and 4 cycles of adjuvant docetaxel (75 mg/m2 q21d + prednisone) in high risk, localized prostate cancer. Methods: From2006-2014,38 patients were enrolled. Acute hematologic as well as acute and chronic gastrointestinal (GI) and genitourinary (GU) toxicities were scored based on the CTCAE v3.0 criteria. Biochemical recurrence was defined as a nadir + 2 rise in PSA. Actuarial freedom from PSA failure (bNED) and overall survival (OS) were calculated using SPSS v24. Median Gleason score was 8 (74% Gleason 8-10). Median PSA was 11.2 (range 2.8-96). Results: A total of 38 patients were enrolled on the trial. Median age was 62 years (range 45-82). 82% of patients completed all protocol specified treatments, while 84% completed all 4 cycles of docetaxel. After a median follow up of 44 mo (range 3.4-118), the 5-year bNED rate was 86% while 5-year OS was 80%. Acute grade ≥ 2 GI and GU toxicity rates were 12.5% and 21.9%, respectively. Chronic grade ≥ 2 GI and GU toxicity rates were 3.1% and 3.1%, respectively. 25.6% (n = 10) patients receiving docetaxel developed grade 4 hematologic toxicity. There were no grade 5 toxicities. Conclusions: We found this aggressive multi-modal approach to be feasible, safe, well-tolerated, and effective. It does not appear that BMS-PR decreases hematologic toxicity. Cs-131, with its 9.7 day half-life, does not appear to increase acute or late toxicity. These data build upon the ASCENDE-RT and RTOG 0521 trials that demonstrate the added benefits of brachytherapy boost and adjuvant docetaxel, respectively, in high-risk prostate cancer.

Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years.

To evaluate the long-term outcomes of high-dose-rate (HDR) brachytherapy for patients with intermediate- and high-risk prostate cancer. We retrospectively analysed a prospective longitudinal cohort database including a single-surgeon series of 507 consecutive men treated with external beam radiotherapy and an HDR prostate brachytherapy boost between August 2000 and December 2009. The risk factors used were based on the D'Amico classification. We measured the incidence of no biochemical evidence of disease (bNED) based on the Phoenix definition of failure (nadir PSA + 2 ng/mL). We also reviewed the incidence of urethral stricture in this cohort. With minimum and median follow-ups of 6 and 10.3 years, respectively, the bNED rates for men with intermediate- and high risk disease were 93.3% and 74.2%, respectively, at 5 years and 86.9% and 56.1%, respectively, at 10 years. The 10-year bNED rate for men with only one intermediate-risk factor was 94%, whereas for patients with all three high-risk factors it was 39.5%. The overall urethral stricture rate was 13.6%. Before 2005, the urethral stricture rate was 28.9% and after January 2005 it was 4.2%. For the 271 men with a minimum follow-up of 10 years the actuarial 10-year prostate cancer-specific survival rate was 90.8% and the actuarial overall survival rate was 86.7%. For men with intermediate- or high-risk prostate cancer features, who are considered not suitable for, or wish to avoid a radical prostatectomy, HDR prostate brachytherapy remains an appropriate treatment option. From December 2004, prevention strategies decreased the risk of post-brachytherapy urethral strictures.

Treatment outcomes with hypofractionated high-dose radiation therapy for prostate cancer

AimTo report the treatment results of a retrospective cohort of prostate cancer patients treated with Hypo-RT with a high equivalent biological effective dose (BED). BackgroundHypofractionated radiotherapy (Hypo-RT) has gained popularity and interest in the treatment of prostate cancer. However, there are few experiences with adequate follow-up reporting treatment results using high equivalent dose with Hypo-RT. Materials and methodsWe assigned 149 men with low-, intermediate- and high-risk prostate cancer to receive Hypo-RT with a total dose of 69Gy/23 fractions. Late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified RTOG criteria. Biochemical no evidence of disease (bNED) was defined as the nadir prostate-specific antigen level plus 2ng/mL. ResultsThe median follow-up was 53 months. For the entire cohort, the 5-year bNED rate was 94.6%, and for low-, intermediate- and high-risk patients the 5-year bNED was 100%, 96.4%, and 86% (p=0.007), respectively. The 5-year overall survival rate was 92%. Only 1 patient died from the disease at 48 months after treatment, giving a 5-year cancer-specific survival of 98%. The worst grade ≥2 rate GI and GU toxicity was 13.4% and 14%, respectively. No grade >3 toxicity was observed. The presence of grade ≥2 GI and GU toxicity at the last follow-up was only 1.3% and 3%, respectively. ConclusionsHypo-RT (69Gy/23 fractions) with a high equivalent BED produces excellent rates of biochemical control for low, intermediate and high-risk prostate cancer. The long term GU and GI toxicity rates were considered low and acceptable.

Long-term outcome of early stage prostate cancer treated with brachytherapy analysis after a mean follow-up of 7 years.

PurposeTo investigate the long-term efficacy of 125I brachytherapy in early-stage prostate cancer and to identify correlating factors.MethodsThis study included 117 cases of early stage prostate cancer. The patients ranged in age from 51 to 84 years, with a mean of 73 years. The features of the study population were as follows: the PSA ranged from 0.4 to 47.6 ng/ml (median, 14.7); the Gleason score ranged from 4 to 9 (mean, 6.4); the clinical stage ranged from T1b to T2c; and the positive biopsy rate ranged from 0.08 to 1.0 (mean, 0.45). The mean D90 was 142 Gy and ranged from 106 Gy to 170 Gy. The numbers of low-risk, intermediate-risk and high-risk prostate cancer cases were 22, 29 and 66, respectively. The biochemical no evidence of disease (bNED) rate and overall survival were recorded. Factors that correlated with the outcomes were evaluated.ResultsWith a mean follow up of 84 months, 33 cases had biochemical recurrence, with a bNED rate of 72%. The overall survival rate was 90%, and the cancer-specific survival rate was 97%. The bNED rates in the low-risk, intermediate-risk and high-risk groups were 86%, 79% and 64%, respectively (P = 0.040). The patients with PSA <20 ng/ml, a positive biopsy rate lower than 0.5, and D90 ≥ 140 Gy had lower biochemical recurrence (P = 0.028, 0.006, 0.009, respectively).ConclusionsThe long-term efficacy of 125I brachytherapy in early stage prostate cancer was shown. bNED is related to risk stratification, PSA level, positive biopsy rate and D90.

Brachytherapy in early stage prostate cancer: an average of 7-year follow-up

Objective To investigate the long-term efficacy and complications of brachytherapy in early stage prostate cancer.Methods The data of 117 cases of early stage prostate cancer patients were analyzed,aged from 51 to 84 years,with an average of 73 years.The PSA ranged from 0.4 to 47.6 μg/L (14.7 in average),Gleason score ranged from 4 to 9 (6.4 in average),clinical stage ranged from T1b to T2c,the prostate volume ranged from 13 to 69 ml (31 ml in average),and the positive biopsy rate was 8％to 100％ (45％ in average).The low-risk,intermediate-risk and high-risk prostate cancer were 22,29 and 66 cases.Biochemical no evidence of disease (bNED),overall survival and complications were recorded.Results Followed up from 19 to 114 months (84 months in average),33 cases had biochemical recurrence (bNED rate,72％).Twelve patients died,among which 4 patients died of prostate cancer.The overall survival rate was 90％,and the cancer-specific survival rate was 97％.The bNED rates in low-risk,intermediate-risk and high-risk groups were 86％,79％ and 64％,and the difference was significant among the 3groups (P=0.040).The overall survival rates were 100％,90％ and 86％,with no significant difference among the 3 groups (P=0.189).Urinary retention occurred in 11 cases (9％),among which 1 patient had TURP treatment.No serious complications such as rectal fistula occurred.Conclusions The long-term efficacy of brachytherapy in early stage prostate cancer is definite with few complications.With a mean followup of 7 years,the bNED rate was 72％ and the overall survival rate was 90％. Key words: Prostate neoplasms; Brachytherapy; Efficacy; Follow-up studies

Application of 125I implantation in the elderly prostate cancer patients

Objective To evaluate the clinical safety and efficiency of applying 125I permanent-implant prostate brachytherapy (BRT) in elderly prostate cancer patient treatment.Methods From Jan.2007 to Dec.2011,23 elderly patients (age ≥75 years) with a diagnosis of localized prostate cancer were treated at our institution and then were evaluated retrospectively.The average age was 79.7 (ranged from 75-87) years.The average prostate volume was 52 (ranged from 35-78) ml.PSA level was 6.2±1.5 (ranged from 3.3 to 9.8) μg/L.Seven cases were in T1cN0M0,sixteen cases were in T2aN0M0.Five cases were with Gleason score of 4,two cases were with Gleason score of 5,sixteen cases were with Gleason score of 6.All patients received a single 125I permanent-implant brachytherapy with a total dosage of 145 Gy.Patients were stratified according to biochemical recurrence-free survival (bDFS),overall survival rate (OS) and complications.All the patients had not accepted anti-androgen therapy or external radiotherapy.Results The average followed up were 50 (ranged from 4 to 77) mon.After 3 months,the average serum PSA was 2.4±0.4(ranged from 0.9-3.8) μg/L,there was significant difference compared with that before treatment (P=0.003).After 1 years,the average serum PSA was 0.2-2.7 μg/L and 87％ (20/23) patient's PSA was less than 1 μg/L.2 cases had biochemical recurrence (bNED rate,91％).4 patients died,among them 1 patients died of prostate cancer.The overall survival rate was 83％,and the cancer-specific survival rate was 96％.Of the patients with urethral adverse effects,0-V adverse effect rates were 34.8％,43.5％,17.4％,4.3％,0 and 0.No serious complication such as rectal fistula occurred.Conclusions BRT is an effective and safe monotherapy in elderly prostate cancer patients. Key words: Prostate cancer; Brachytherapy; Elderly patients; Efficacy

Comparison between preoperative and real-time intraoperative planning 125I permanent prostate brachytherapy: long-term clinical biochemical outcome

BackgroundThe purpose of the study is to evaluate the long-term clinical outcome through biochemical no evidence of disease (bNED) rates among men with low to intermediate risk prostate cancer treated with two different brachytherapy implant techniques: preoperative planning (PP) and real-time planning (IoP).MethodsFrom June 1998 to July 2011, 1176 men with median age of 67 years and median follow-up of 47 months underwent transperineal ultrasound-guided prostate 125I-brachytherapy using either PP (132) or IoP (1044) for clinical T1c-T2b prostate adenocarcinoma Gleason <8 and prostate-specific antigen (PSA) <20 ng/ml. Men with Gleason 7 received combination of brachytherapy, external beam radiation and 6-month androgen deprivation therapy (ADT). Biological effective dose (BED) was calculated using computerized tomography (CT)-based dosimetry 1-month postimplant. Failure was determined according to the Phoenix definition.ResultsThe 5- and 7-year actuarial bNED rate was 95% and 90% respectively. The 7-year actuarial bNED was 67% for the PP group and 95% for the IoP group (P < 0.001). Multivariate Cox regression analyses identified implant technique or BED, ADT and PSA as independent prognostic factors for biochemical failure.ConclusionsFollowing our previous published results addressing the limited and disappointing outcomes of PP method when compared to IoP based on CT dosimetry and PSA kinetics, we now confirm the long-term clinical, bNED rates clear cut superiority of IoP implant methodology.

Comparison of seed brachytherapy or external beam radiotherapy (70 Gy or 74 Gy) in 919 low-risk prostate cancer patients

The aim of this analysis was to compare the biochemical no evidence of disease (bNED) rates in low-risk prostate cancer patients treated at two centers of excellence using different approaches: seed brachytherapy (BT) and external beam radiotherapy (EBRT). A total of 919 low-risk prostate cancer patients, treated from 1998-2008, were identified in the two databases. In Utrecht, 667 patients received I-125 BT applying a dose of 144Gy. In Vienna, 252 patients were treated with EBRT, applying a local dose of 70Gy in 82 patients and 74Gy in 170 patients. bNED rates (Phoenix definition) were assessed. The median follow-up was 46 months (range 1-148months). The 5-year actuarial bNED rates were 94% for BT patients and 88% for EBRT patients (p = 0.002)-84% for patients receiving 70Gy and 91% for patients receiving 74Gy, respectively. In the univariate analysis, patients receiving 70Gy showed significantly worse outcome compared to BT (p = 0.001) and a difference close to significance compared to 74Gy (p = 0.06). In the multivariate analysis including tumor stage, Gleason score, initial PSA, hormonal therapy, and dose, patients receiving 70Gy EBRT showed significantly worse bNED rates compared to BT patients. Low-risk prostate cancer patients receiving 74Gy by EBRT show comparable biochemical control rates to patients receiving seed brachytherapy, whereas patients receiving 70Gy show significantly worse outcome.

Biochemical outcomes for patients with intermediate-risk, organ-confined prostate cancer treated with I-125 interstitial brachytherapy monotherapy.

192 Background: Treatment with low dose rate brachytherapy (LDR-BT) monotherapy is well established for low risk prostate cancer. The routine use of LDR-BT in intermediate risk (IR) is more controversial and is often combined with additional external beam radiotherapy (EBXRT). We report the biochemical outcome of a large cohort of patients with IR disease treated with LDR-BT monotherapy. Methods: A multi-institutional prospective database identified 615 patients with IR prostate cancer treated with I-125 interstitial BT between 2003–2007. IR was defined using Memorial Sloan-Kettering Cancer Centre (MSKCC) definition of either T2b, or Gleason score (GS) 7 or raised initial PSA (iPSA) 10.1-20ng/ml. Patients receiving additional EBXRT were excluded. Biochemical failure was defined by both ASTRO (3 rises past nadir) and Phoenix criteria (nadir plus 2). Kaplan-Meier methods were used to estimate biochemical no evidence of disease rates (bNED) and univariate analyses used to identify potential prognostic factors. Results: The median age was 64 years (range 49–82). Forty-three patients had stage T2b, 180 had iPSA 10.1-20 and 392 had GS 7 disease. Only 108 received androgen deprivation therapy (ADT) prior to implant. Median follow up was 5.0 years. The 5-year bNED rates (95% confidence interval) by ASTRO are 85.5% (82.0–88.3%) and for Phoenix 83.7% (80.0–86.7%). Use of ADT, GS 3+4 versus 4+3, and dosimetric indices were not significant prognostic variables. When stratified by risk factor (T2b, GS7 or raised iPSA) raised iPSA correlated to poorer outcome only by Phoenix criteria (by Phoenix p=0.001, by ASTRO p=0.311). Conclusions: We have demonstrated good biochemical control for IR patients treated with LDR-BT alone. No additional benefit was seen with the use of ADT. We believe LDR-BT alone is an effective treatment option in selected IR prostate cancer patients with comparable outcome to other treatment modalities such as surgery or EBXRT.

Outcomes following iodine-125 brachytherapy in patients with Gleason 7, intermediate risk prostate cancer: A population-based cohort study

Background and purposeTo evaluate outcome in patients with Gleason 7 prostate cancer treated with iodine-125 brachytherapy at the British Columbia Cancer Agency. Materials and methodsBetween 20th July 1998 and 7th February 2006, 1500 patients underwent I-125 prostate brachytherapy without supplemental external beam radiation therapy. Of these, 439 had Gleason 7 disease; 362 had Gleason 3+4 and 77 had 4+3 disease. Generally, patients received 6months of androgen suppression. We compared biochemical no evidence of disease (bNED) between patients with Gleason ⩽6 and Gleason 7 and between Gleason 3+4 and 4+3 using the Phoenix definition of biochemical recurrence. ResultsMedian follow-up was 60months. Estimated 5year bNED was 97% for patients with Gleason score ⩽6 and 94% for patients with Gleason 7 disease (p=0.037). Estimated bNED was 95% and 94% for 3+4 and 4+3, respectively (p=0.791). There was no difference in bNED between implants achieving D90⩾versus<the median value (150.5Gy) or⩾versus<140Gy. ConclusionsI-125 brachytherapy with 6months of ADT demonstrates excellent bNED rates in Gleason 7 disease. We found no evidence of a difference between patients with Gleason 3+4 versus 4+3 disease.

CT Based Dosimetry Following Low Dose Rate (LDR) Prostate Brachytherapy in 2787 Consecutive Cases over 11 Years

To examine trends in CT based dosimetry within a large, multi-practitioner LDR prostate program. Our program was established on 1/11/97 and developed a planning/treatment algorithm that attempted to incorporate the most workable components of existing programs; the first implant was done 20/07/98. Initially all implants were done by four Radiation Oncologists usually working in pairs. After ˜3 years, a formal 6-12m training program was introduced; today 14 Radiation Oncologists participate and 2787 consecutive implants are included in this analysis. Model 6711 (Oncura) 125Iodine sources of 0.33 mCi (NIST99) were used for >99% of implants, 333 of the first 361 used loose seeds, the remaining 2454 employed RapidStrand. Day-30 CT was standard for the first 1604, after which day-0 CTs were substituted. CT dosimetry is available for 98% (N = 2734). In general, the Radiation Oncologist who did the implant also contoured the CT images. The first 1500 patients in the cohort have a median FU of 60m (range 0-135.4m) and this subset was used to calculate the KM biochemical no evidence of disease (bNED) rates using the Phoenix definition. Among this subset, 832 had low risk; 668 intermediate risk and 4 high risk disease. Two thirds (N = 958) received 6m of adjuvant androgen deprivation therapy (ADT). The 5, 7 and 10y KM bNED rates (±95% CI) are 96.0 ±1.2%, 93.9 ± 1.8% and 93.0 ± 2.0%. D90 and V100 were not predictive of bNED in univariate or multivariate analysis. The means (±SD) for D90 (expressed as % of prescription dose), V100, and V150 are 104.8 ± 9.7%, 91.9 ± 5.3% and 52.7 ± 12.0%. A learning curve effect is seen; the mean D90% and V100 for our first 100 implants are lower than for the rest (96.4 vs. 106.5%; 85.5 vs. 92.1%, p < 0.001) and the proportion of implants failing to reach quality assurance (QA) thresholds (D90% ≥90%, V100 ≥85%) declined with time. Nearly 1/3 (31) of first 100 implants had D90 <90%, which applied to 15.3% of the next 500 implants and only 2.8% of the remaining 2187. The V100 results are virtually identical. In contrast, the mean (±SD) V150 was 45.3 ± 14.6% in the first 100 implants, gradually rose to a wide peak of >60% for implants 400-800 inclusive, and then declined to a plateau of just under 50% (48.8 ± 10.5%) for the most recent 1000 cases. An improving therapeutic ratio is suggested by a decreasing V150 in the presence of better dose coverage and may reflect increasing reliance on stranded sources to provide both central sparing with enhanced extraprostatic coverage. About 500 cases were completed before more than 95% reliably met QA thresholds; ironically, but fortunately, these arbitrary thresholds proved to be poor predictors of biochemical failure in this series.