After ASCENDE-RT: Biochemical and survival outcomes following combined external beam radiotherapy and low-dose-rate brachytherapy for high-risk and unfavourable intermediate-risk prostate cancer,a population-based analysis

PURPOSETo evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB).METHODS AND MATERIALSA population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial.RESULTSThe median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p < 0.001), 73 ± 8% (p < 0.001), and 77 ± 9% (p = 0.098) for the ineligible patients.CONCLUSIONSIn this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.     

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.     

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.     

Risk factors for biochemical recurrence after a tissue-ablative prostate-specific antigen <0.2 ng/mL

PurposeA prostate-specific antigen (PSA) nadir <0.2 ng/mL is generally considered as tissue ablative and at low risk for recurrence. After attaining such a low PSA nadir, we analyzed risk factors for recurrence.Methods and materialsWe identified patients from our institutionalized database with either D'Amico low- or intermediate-risk prostate cancer that was treated with either low-dose-rate prostate brachytherapy or external beam radiotherapy as monotherapy. We compared patients who attained a nadir <0.2 ng/mL and subsequently developed biochemical failure to patients who did not experience biochemical failure by using χ² test and Student t test. Survival analysis was performed using the Kaplan–Meier method (log-rank test).ResultsOf 892 patients, 560 (63%) achieved a nadir <0.2 ng/mL. Only 23 (4.1%) later developed a biochemical recurrence. The 7-year Kaplan–Meier biochemical recurrence-free survival after a PSA nadir of <0.2 ng/mL was 96%. Patients who later experienced biochemical recurrence were more likely to have Cancer of the Prostate Risk Assessment Score intermediate- or high-risk cancer: (74% vs. 40%, p < 0.001). Patients were more likely to have a diagnostic PSA >6.0 ng/mL: (66% vs. 43% p < 0.001) and have a Gleason score ≥ 3  + 4: (52% vs. 34%, p = 0.005). They were also more likely to be older (p = 0.003): mean (SD) 70.3 (6.4) vs. 66.2 (6.5) and have a time to PSA nadir that was significantly shorter (p = 0.013): mean (SD) 51.8 (29.6) vs. 65.2 (25.1).ConclusionsBiochemical recurrence after attaining a PSA nadir <0.2 ng/mL is rare and more frequent in patients with intermediate risk cancer and older patients. These patients can benefit from a prolonged followup with specialized physicians.     

Time to achieve a prostate-specific antigen nadir of ≤0.2 ng/mL and related factors after permanent prostate brachytherapy

PurposeThe purpose of this study was to identify the time to achieve a prostate-specific antigen (PSA) nadir of ≤0.2 ng/mL and the related factors to achieve this goal.Materials and MethodsWe retrospectively reviewed 2218 Japanese prostate cancer patients who received ¹²⁵I brachytherapy with or without external beam radiotherapy between 2003 and 2013 at one institution. Among them, patients followed up for ≥72 months and without luteinizing hormone–releasing hormone (LH-RH) agonist/antagonist were included (total of 1089 patients). The time to a PSA nadir of ≤0.2 ng/mL (months) was defined as the time between the date of implantation and the first time the lowest PSA value reached ≤0.2 ng/mL. Biochemical recurrence (BCR) was determined using the Phoenix definition. Multivariate linear regression analysis was performed to detect the related factors to achieve this nadir.ResultsWe assigned 409, 592, and 88 patients to the low-, intermediate-risk, and high-risk groups, respectively. The median followup time was 9.5 years. The median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 (95% confidence interval: 42.3–45.7) months. The percentage of patients that achieved the nadir was 89.1%. BCR was noted in 107 (9.8%) patients. In the multivariate analysis of patients without BCR, younger age, larger prostate volume at implantation, higher initial PSA level, and monotherapy were significantly associated with longer time to achieve the PSA nadir.ConclusionThe median time to achieve a PSA nadir of ≤0.2 ng/mL was 44.0 months. Some patients, however, may require a lengthy period of time to do so.     

Four-year outcomes of hypofractionated high-dose-rate prostate brachytherapy and external beam radiotherapy

PurposeHigh-dose-rate (HDR) brachytherapy boost in prostate cancer allows dose escalation and delivery of higher biologically effective dose (BED). We evaluated the outcomes of intensity-modulated radiation therapy (IMRT) and HDR boost in a community setting.Methods and MaterialsBetween July 2003 and April 2008, 148 patients with prostate cancer were treated at Cancer Center of Irvine using two transperineal implants performed 1 week apart (22 Gy delivered in four fractions divided between two insertions and delivered twice daily), followed by IMRT (50.4 Gy). Hormonal therapy was given for 1 year to all patients with Gleason score of 8 or higher.ResultsPatient characteristics are as follows: median age at treatment, 71 years; American Joint Committee on Cancer Group IIB, 53%; Gleason score of 7, 41%; and Gleason score of 8 or higher, 14%. Median followup was 49 months, and median prostate-specific antigen (PSA) nadir was 0.15 ng/mL. The 4-year actuarial biochemical disease-free survival (bDFS) was 96.8/81% by Phoenix/PSA lower than 0.5 ng/mL criteria. According to National Comprehensive Cancer Center Clinical Practice Guidelines–defined recurrence risk groups, 4-year bDFS for low risk was 100/92.9%, intermediate risk was 100/86.7%, and high risk was 94/75.4% by Phoenix/PSA lower than 0.5 ng/mL criteria. No statistically significant difference in bDFS was detected by either failure criteria based on risk group, lymph node risk, or initial PSA. Treatment was well tolerated. Subacute/late genitourinary and gastrointestinal toxicities were limited to 10% and 5%, respectively of all patients.ConclusionsProstate IMRT plus HDR brachytherapy boost was well tolerated with appropriate PSA response and bDFS at 4 years, demonstrated in a community setting. This treatment schema provides a high BED, comparable with hypofractionated prostate regimens previously reported in the literature. Higher BED delivery should be explored in further dose escalation studies.     

Cesium-131 prostate brachytherapy: A single institutional long-term experience

AimsTo report on the PSA outcomes in men undergoing prostate seed implant (PSI) with Cesium-131 at a single institution.Materials and MethodsAll patients who underwent prostate brachytherapy with Cesium-131 (¹³¹Cs) at our institution and had the potential for at least 24 months of follow up were included in this study. Results are reported for the by NCCN risk group (low, low/high-intermediate, and high), as well as by treatment received (monotherapy, combination external beam radiation + PSI, or trimodal therapy with androgen deprivation). The Phoenix definition (absolute nadir plus 2 ng/mL) was used to define biochemical freedom from disease (BFD).ResultsEight hundred and six men have undergone prostate brachytherapy with Cesium-131 at our institution, and 669 men were included in analysis. Median follow up was 60.0 months (range: 0–144 months). According to NCCN risk categories, 29.9% were low-, 55.6% intermediate-, and 14.5% high-risk. Using the Phoenix criteria, 5/10-year BFD was 97.1/95.3% for patients in the low-risk category, 94.0/90.1% for patients in the intermediate-risk category, and 86.2/56.6% for patients in the high-risk category. PSA ≤0.2 ng/dL at 4 years was predictive of 10 year biochemical control: 96.3% vs 70.4%, p < 0.001.ConclusionsThe present study demonstrates that prostate brachytherapy with ¹³¹Cs achieves excellent long-term biochemical control.     

PSA outcomes and late toxicity of single-fraction HDR brachytherapy and LDR brachytherapy as monotherapy in localized prostate cancer: A phase 2 randomized pilot study

PURPOSETo evaluate the PSA outcomes and the late patient's reported health related quality of life (HRQOL) and toxicity after single-fraction High-Dose-Rate brachytherapy (HDRB) and Low-Dose-Rate brachytherapy (LDRB) for prostate cancer.METHODSMen with low and favorable intermediate-risk prostate cancer across 3 centres were randomized between monotherapy brachytherapy with either Iodine-125 LDRB or 19 Gy single-fraction HDRB. Biochemical outcomes were evaluated using the Phoenix definition, PSA nadir and absolute PSA value <0.4 ng/mL. Toxicities and HRQOL were recorded at 24 and 36 months.RESULTSA total of 31 patients were randomized, 15 in the LDRB arm and 16 patients in the HDRB arm. After a median follow-up of 45(36–53) months, 3 patients in the HDRB arm experienced biochemical failure (p = 0.092). Nineteen Gy single-fraction HDRB was associated with significantly higher PSA nadir compared to LDRB (1.02 ± 0.66vs 0.25 ± 0.39, p < 0.0001). Moreover, a significantly larger proportion of patients in the LDRB group had a PSA <0.4 ng/mL (13/15 vs 2/16, p < 0.0001). For late Genito-Urinary, Gastro-Intestinal, and sexual toxicities at 24 and 36 months, no significant differences were found between the 2 arms. As for HRQOL, the IPSS and EPIC-26 urinary irritative score were significantly better for patients treated with HDRB over the first 36 months post-treatment (p = 0.001 and p = 0.01, respectively), reflecting superior HRQOL.CONCLUSIONHDRB resulted in superior HRQOL in the irritative urinary domain compared to LDRB. PSA nadir was significantly lower in the LDRB group and a higher proportion of patients in the LDRB group reached PSA <0.4 ng/mL.     

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.     

PSA bounce after prostate brachytherapy with or without neoadjuvant androgen deprivation

PurposeTo assess the impact of PSA bounce (PB) on biochemical failure (BF) and clinical failure (CF) in brachytherapy patients treated with or without neoadjuvant androgen deprivation (AD).Methods and MaterialsFrom 1987 to 2003, 691 patients with clinical stage T1–T3N0M0 prostate cancer were treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy boost (n = 407), HDR brachytherapy alone (n = 93), or permanent seed implant (n = 191). Three hundred seventeen patients (46%) received neoadjuvant/adjuvant AD with RT. BF was scored using 3 definitions (ASTRO—3 rises, nadir + 2 ng/ml, and threshold 3 ng/ml) based on current and absolute nadir (AN) methodologies. PB was defined as any increase in PSA followed by a decrease to the prior baseline or lower. The median followup was 4.0 years.ResultsForty-six patients (7%) experienced CF at 5 years. PB of ≥0.1, ≥1.0, and ≥2.0 ng/ml at any time after RT occurred in 330 (48%), 60 (9%), and 22 patients (3%) respectively. The use of an AN definition reduced the likelihood of scoring PB as BF across all levels. The patients receiving AD experienced significantly longer bounce duration. Bounce <1.0 ng/ml showed no association with CF. For bounce ≥1.0 ng/ml, 10% demonstrated CF vs. 6% without bounce of this amplitude (p = 0.27). Bounces ≥1.0 ng/ml were more likely to be scored as BFs for definitions based on current nadir (3 rises: 20% vs. 13%, nadir + 2: 43% vs. 11%, 3 at/after nadir: 57% vs. 12%) than those based on AN (3 rises: 8% vs. 10%, nadir + 2: 18% vs. 11%, 3 at/after nadir: 13% vs. 11%).ConclusionsBounces ≥1.0 ng/ml are rare after brachytherapy with or without neoadjuvant AD, occurring in less than 10% of patients. Low PBs have little impact on BF, but as PB amplitude increases, the BF rate increases. BF definitions based on AN are less sensitive to PB after brachytherapy.     

A comparative analysis of overall survival between high-dose-rate and low-dose-rate brachytherapy boosts for unfavorable-risk prostate cancer

Purpose

External beam radiation therapy (EBRT) with low-dose-rate (LDR) brachytherapy boost has been associated with improved biochemical progression–free survival and overall survival (OS) compared with dose-escalated EBRT (DE-EBRT) alone for unfavorable-risk prostate cancer. However, it is not known whether high-dose-rate (HDR) boost provides a similar benefit. We compare HDR boost against LDR boost and DE-EBRT with respect to OS.

High-dose-rate brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience

PurposeTreatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT.Patients and MethodsSix men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound–guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36 Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30 Gy, received 24 Gy in four fractions.ResultsMedian age was 67.5 (56–74) years. At a median followup of 26 (14–60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19 ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3–5 toxicity.ConclusionTransperineal ultrasound–guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.     

Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer

PurposeThe recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer.Methods and materialsA multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data.ResultsThe estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions.ConclusionsIMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.     

Biochemical disease-free survival rates following definitive low-dose-rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide

PURPOSE: To report biochemical disease-free survival (bDFS) after conformal brachytherapy with dose escalation to biological target volumes (BTVs) identified by Capromab Pendetide with single photon emission computed tomography and computed tomography image fusion (SPECT/CT). METHODS AND MATERIALS: Two hundred thirty-nine (T1c-T3b NxM0) consecutive patients were evaluated by SPECT/CT before treatment. Intraprostatic SPECT/CT BTVs were identified and targeted for 150% dose escalation during brachytherapy seed implant (SI). Patients received either SI alone (n = 150) or external beam radiation therapy (EBRT) plus SI boost (EBRT+SI) (n = 89), with (n = 50) and without (n = 189) neoadjuvant hormone ablation therapy. Risk factors (RF) (prostate-specific antigen [PSA] >10 ng/mL, Stage > or = T2b, and Gleason grade > or = 7) defined risk group (RG) categories [none, 1, and > or = 2 RF define low, intermediate, and high RG] for bDFS calculations using four failure criteria: American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition, PSA >1.0 ng/mL (PSA >1), PSA >0.5 ng/mL after nadir (PSA >0.5), and PSA nadir+2 ng/mL rise in PSA clinical nadir (CN+2). Median followup was 47.2 months (range, 24.8-96.1). RESULTS: Seven-year actuarial bDFS rates were 88.0%, 82.1%, 80.4%, and 79.9% using the ASTRO, PSA >1, PSA >0.5, and CN+2 failure criteria, respectively. ASTRO-defined bDFS rates were 96.0%, 87.0%, and 72.5% for low, intermediate, and high RG's. CONCLUSION: The data presented here demonstrate the feasibility of performing SPECT/CT BTV dose escalation in a mature series.     

Is hemi-gland focal LDR brachytherapy as effective as whole-gland treatment for unilateral prostate cancer?

PURPOSEThe Hemi-Ablative Prostate Brachytherapy (HAPpy) trial evaluated hemi-gland (HG) low-dose-rate prostate brachytherapy (LDR-PB) as a focal approach to control unilateral localized prostate cancer and reduce treatment-related toxicity at 2-years postimplant. Herewith we present further outcomes with a minimum of 5 years post-implant follow-up.METHODS AND MATERIALSOutcomes of 30 HG implants and 362 whole-gland (WG) brachytherapy controls were monitored with IPSS, urinary Quality-of-Life (QoLU), GI component of EORTC-PR25 (QoLB), and IIEF-5 instruments, and PSA values. The median (range) follow-up for HG and WG cases was 72 (60–96) months and 84 (24–144) months respectively.RESULTSThe IPSS was significantly reduced in HG relative to WG patients and trends indicating improved bowel QoL and erectile function were observed. The mean of change in PSA from baseline to last follow-up was -5.6 and -6.5 in HG and WG respectively (p = 0.1). The mean time to nadir was 4.2 and 4.8 years in HG and WG respectively (p = 0.06). Over time PSA in HG patients mirrored the sustained decline observed in WG cases but levels were higher by an average 0.5 ng/ml over WG controls (p < 0.001). Treatment failure occurred in 2 (6.7%) HG patients and in 20 (5.5%) WG cases. Five-year relapse-free survival was 97% in both groups (p = 0.7).CONCLUSIONSAt 5 years postimplant HG LDR-PB was as effective as WG treatment for control of unilateral localized prostate cancer with moderate improvement in treatment-related symptoms. Importantly, PSA is a valuable marker to assess disease control in this form of focal therapy.     

Selection of patients who would not require long-term prostate-specific antigen monitoring after low-dose-rate brachytherapy

PurposeTo identify patients at extremely low risk of biochemical recurrence (BCR) of prostate cancer after low-dose-rate brachytherapy (LDR-BT) to determine when prostate-specific antigen (PSA) monitoring can be stopped.Methods and MaterialsWe retrospectively reviewed clinicopathologic data of patients with prostate cancer who underwent LDR-BT between 2003 and 2011. Of 1569 patients reviewed, 689 (43.9%) received combination external beam radiotherapy, and 970 (61.8%) had neoadjuvant hormonal therapy. We stratified patients according to risk factors identified by multivariate analysis and assessed the factors for an association with BCR (defined as ≥2 ng/mL higher than the nadir).ResultsThe median followup was 96 months. Of 1531 patients who were BCR-free at 3 years after treatment, 76 subsequently developed BCR; of 1500 who were BCR-free at 5 years, 45 eventually had BCR. On multivariate analysis, independent risk factors for BCR were the National Comprehensive Cancer Network risk group at diagnosis and PSA levels at 3 or 5 years after radiotherapy. In the low-risk group, no patient with a PSA level ≤0.2 ng/mL at 3 years after radiotherapy subsequently developed BCR. In the intermediate-risk group, no patients with a PSA level ≤0.2 ng/mL at 5 years subsequently developed BCR.ConclusionsThe National Comprehensive Cancer Network risk group at diagnosis and PSA values at 3 and 5 years after LDR-BT are independently associated with a risk of later BCR. Using these two factors may help to select patients for whom PSA monitoring could be stopped because they have an extremely low risk of later BCR.     

National patterns of care for early-stage penile cancers in the United States: How is radiation and brachytherapy utilized?

PurposePer American Brachytherapy Society guidelines, cT1-2N0 penile cancers <4 cm in diameter are excellent candidates for curative brachytherapy. Using that criterion, we evaluated national patterns of care and predictors of use of radiation techniques using the National Cancer Database.Methods and MaterialsThe National Cancer Database was queried for men with cT1-2N0 penile cancers <4 cm in size. Comparative statistics for treatment modality were generated using bivariate logistic regression analysis.ResultsAmong 1235 cases eligible for analysis, median age was 69 years. Median tumor size was 2.0 cm. 95.8% of men underwent surgery alone, with 91 (7.4%) undergoing radical penectomy, 673 (54.5%) partial penectomy, and 419 (33.9%) cosmesis-preserving surgical procedure. Only 4 (0.3%) men were treated with brachytherapy alone, 48 (3.9%) with external-beam radiation therapy (EBRT) alone, and 8 (0.6%) with EBRT after surgery. Surgical margins were positive in 118 (9.6%) patients, 14 of whom received adjuvant EBRT (11.9%) and two adjuvant brachytherapy (1.7%).There was no difference in demographic or clinical characteristics in groups treated with surgery vs. radiation (all p > 0.2). Age >70, lesions >2 cm, and T2 tumors were more likely to undergo non–organ-preserving therapy vs. radiation or a cosmesis-preserving procedure (all p < 0.05). The propensity-matched 5-year survival was not different between definitive radiation vs. surgery (61.6% vs. 62.2%, p = 0.70).ConclusionsMen with penile-preserving eligible lesions in the United States are overwhelmingly treated with surgery. Penile-preserving radiation techniques including brachytherapy and EBRT are underutilized and should be offered as curative interventions.     

Prostate-specific antigen spikes with 131Cs brachytherapy. Is there a difference with other radioisotopes?

PurposeThere is a suggestion that a dose-rate effect exists for the prostate-specific antigen (PSA) spike after brachytherapy. ¹³¹Cs is a newer radioisotope with a half-life of 9.7 days that is being used for prostate brachytherapy. There is no published data on the PSA spike with this radioisotope and the goal of this study was to quantify PSA spikes with ¹³¹Cs and compare it with published data for other isotopes.Methods and MaterialsWe have been maintaining a prospective database for all patients treated with ¹³¹Cs prostate brachytherapy at our institution. We selected patients for whom followup PSA was available for at least 24 months. The PSA spike was defined as an increase of 0.2 ng/mL, followed by a decline to prespike level.ResultsOne hundred twenty-three patients had monotherapy, whereas 32 had external beam radiation therapy followed by a brachytherapy boost. Median followup was 36 months and mean numbers of PSAs obtained were 7. Forty-six (29.7%) patients had a PSA spike. The mean time and duration for the PSA spike were 12.5 and 8.8 months, respectively. The mean magnitude of increase and mean PSA value at increase were 0.63 and 1.56 ng/mL, respectively.ConclusionsThe incidence of a PSA spike in our series is consistent with reported numbers for other radioisotopes. The occurrence of the spike at 12.5 months appears to be at the early end of the spectrum reported for ¹²⁵I, but the duration and magnitude are similar to other radioisotopes.     

Transperineal mapping biopsy improves selection of brachytherapy boost for men with localized prostate cancer

PURPOSETo determine if transperineal mapping biopsy (TPMB) can improve the selection of brachytherapy alone (BT) or brachytherapy boost (BTB) in men with localized prostate cancer.Methods and MaterialsTwo hundred and eighteen men underwent TPMB with a mean of 48.6 cores retrieved. Comparisons were made between prebiopsy risk features and biopsy results to treatment choice with associations tested with ANOVA (bootstrap), χ² test (Pearson), and linear regression. Survival estimates were tested by the Kaplan–Meier method with comparisons by log rank.ResultsMean age, prostate specific antigen (PSA), prostate specific antigen density (PSAD), and prostate volume were 67.2 years, 8.1 ng/mL, 0.19, and 50.3 cc, respectively. 105 (48.2%) biopsies were positive for Gleason Group (GG) 1: 34 (32.4%), 2: 21 (20%), 3: 31 (29.5%), 4: 7 (6.7%), and 5: 12 (11.4%). The mean number of positive cores (PCs) was 7.3 (median 6, range 1–37). Men with six or more PCs had higher PSA (11.3 vs. 6.0 ng/mL, p = 0.025) and PSAD (0.34 vs. 0.13, p = 0.013). Overall brachytherapy was used in 74 (70.5%) as either monotherapy or boost therapy. Men with BTB had higher PSA (9.7 vs. 6.7 ng/mL, p = 0.029), PSAD (0.27 vs. 0.16, p = 0.007), GG (3.3 vs. 1.8, p < 0.001), more bilateral disease (75.9% vs. 55.6%, odds ratio 3.9, p = 0.008), and PCs (10.9 vs. 4.4, p < 0.001). On linear regression, only GG (p = 0.008) and PCs (p = 0.044) were associated with BTB. Biochemical-free failure at 5 years was 92.7%.ConclusionsTPMB improves the selection of patients for BTB. Men with more PCs are more likely to have BTB. Restricting the need for BTB to those with greater volume prostate cancer may reduce radiation side effects.     

Clinical outcomes of high-dose-rate brachytherapy and external beam radiotherapy in the management of clinically localized prostate cancer

PurposeTo report prostate-specific antigen (PSA) relapse-free survival and treatment-related toxicity outcomes after combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for patients with clinically localized prostate cancer.Methods and MaterialsBetween 1998 and 2009, 229 patients were treated with HDR brachytherapy followed 3 weeks later by supplemental EBRT. The HDR brachytherapy boost consisted of three fractions of ¹⁹²Ir (5.5–7.5 Gy per fraction), and EBRT consisted of intensity-modulated radiotherapy delivering an additional 45.0–50.4 Gy directed to the prostate gland and seminal vesicles. Median follow-up was 61 months.ResultsSeven-year PSA relapse-free survival for low-, intermediate-, and high-risk patients were 95%, 90%, and 57%, respectively (p < 0.001). Among high-risk patients treated with biological equivalent doses in excess of 190 Gy, 7-year PSA relapse-free survival was 81%. In multivariate analysis, Gleason scores of ≥8 predicted for increased risk of biochemical failure, whereas the use of short-term neoadjuvant androgen deprivation therapy did not influence tumor-control outcomes even among intermediate- or high-risk patients. Seven-year incidence of distant metastases for low-, intermediate-, and high-risk patients were 5%, 3%, and 17%, respectively. Seven-year incidence of late Grade 2 and 3 genitourinary toxicities were 22.1% and 4.9%, respectively and the 7-year incidence of Grade 2 and 3 gastrointestinal toxicities were 1% and 0.4%, respectively.ConclusionHDR prostate brachytherapy in conjunction with supplemental EBRT results in excellent biochemical relapse-free survival rates with a low incidence of severe late genitourinary or gastrointestinal toxicities. The use of short-term neoadjuvant androgen deprivation did not influence long-term biochemical tumor control in this cohort.