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Purpose: To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer. Material and methods: Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (125I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer. Results: The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D2cc) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively. Conclusions: Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the nonspacer implants. Further validation of this concept is warranted in clinical trials. [ABSTRACT FROM AUTHOR]

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

Abstract Background Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required. Methods/Design This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (125I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with 125I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during 125I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB. The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events. Discussion To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa. Trial registration UMIN000003992

Brachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy. Of 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ 2 test with survival determined by the Kaplan–Meier method and Cox regression. Men treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150–200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes. Brachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival. [ABSTRACT FROM AUTHOR]

Men with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT). Three hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan–Meier method with associations determined by log rank and Cox regression. Ten-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001). Survival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT. [ABSTRACT FROM AUTHOR]

To determine if transperineal mapping biopsy (TPMB) can improve the selection of brachytherapy alone (BT) or brachytherapy boost (BTB) in men with localized prostate cancer. Two 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. Mean 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%. TPMB 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. [ABSTRACT FROM AUTHOR]

Objectives: To report the long‐term results of prostate brachytherapy followed by external beam radiotherapy (EBRT) in men with a positive seminal vesicle biopsy (+SVB). Patients and Methods: In all, 1081 men with localised prostate cancer were treated with permanent brachytherapy, of which 615 had staging SVB and 53 (9.4%) were positive. Higher stage, Gleason score and PSA level were associated with a +SVB (P < 0.001). Patients with +SVB and negative laparoscopic pelvic lymph node dissection, bone and CT scans had 3 months of androgen‐deprivation therapy (ADT) followed by 103Pd implant to the prostate (dose 100 Gy) and proximal SVs, and 2 months later 45 Gy EBRT. ADT was continued for a median of 6 months (total ADT 9 months). The mean (range) follow‐up was 9 (5–22) years. Results: Biochemical freedom from failure (computed by the Phoenix definition), freedom from metastasis, and cause‐specific survival (CSS) for patients with a negative SVB (–SVB) vs +SVB at 15 years, was 76.3% vs 60.6% (P = 0.001), 95.4% vs 78.2% (P < 0.001), and 95% vs 70.4% (P < 0.001), respectively. Prostate cancer death occurred in 45 of 590 (7.6%) men with a –SVB vs eight of 25 (32%) with a +SVB (odds ratio 5.7, 95% confidence interval 2.35–13.9, P < 0.001). Cox proportion hazard rates (HRs) demonstrated Gleason score (P < 0.001, HR 1.9), stage (P = 0.010, HR 1.42), RT dose (P = 0.013, HR 0.991), and +SVB (P = 0.001, HR 4.48), as significantly associated with CSS. Conclusions: Men with a +SVB have inferior CSS compared to those with a −SVB. However, a strategy that included a SVB in high‐risk patients and implantation of the SVs in men undergoing combined therapy still yields favourable long‐term results. [ABSTRACT FROM AUTHOR]

Objectives: To determine which patient and treatment‐related factors are associated with increased American Urological Association symptom score (AUASS) in men who presented with minimal symptoms before treatment for prostate cancer by permanent seed implantation. Patients and Methods: Of 1842 men with a minimum follow‐up of 5 years (mean 9.4), 1110 (60.3%) had an initial AUASS of 0–7 and were treated with brachytherapy (BT) alone (n = 491) or BT with neoadjuvant hormone therapy (NHT) and/or external beam radiation therapy (EBRT, n = 619). The median prostate volume was 37 mL. Data were prospectively collected on comorbidities. Initial AUASS was compared to last using a Student's t‐test (two‐tailed). Freedom from increasing from minimal to moderate or severe symptoms was determined by the Kaplan–Meier method with comparisons by log‐rank and Cox hazard rates (HRs). Results: The change from pre‐treatment score for the minimal, moderate and severe symptom groups was: 3.6–7.3 (P < 0.001), 11.6–11.3 (P = 0.426), and 24.1–16.9 (P < 0.001). For those with minimal symptoms the 10‐ and 15‐year estimates for freedom from worse symptoms were 72.9% and 39.1%, respectively. Cox HRs were significant for EBRT boost (HR 1.45, P = 0.004), RT dose >200 Gy2 (HR 1.25, P = 0.024), hypertension (HR 1.37, P = 0.006), and alcohol use (HR 1.46, P = 0.001). Conclusion: A substantial number of men with initial low AUASS treated by BT experience worsening urinary symptoms with long‐term follow‐up. Use of EBRT, RT dose, hypertension and alcohol use are risk factors for an increase in urinary symptom score. [ABSTRACT FROM AUTHOR]

Objective To evaluate the cancer control outcomes and long-term treatment-related morbidity of brachytherapy as well as combination brachytherapy and external beam radiation therapy (EBRT) in patients with intermediate-risk prostate cancer. Materials and Methods A retrospective review was conducted in a prospectively collected database of patients with intermediate-risk prostate cancer who were treated either with brachytherapy or brachytherapy and EBRT, with or without androgen deprivation therapy (ADT), in the period 1990--2014. Urinary and erectile dysfunction symptoms were measured using the International Prostate Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual Health Inventory for Men (SHIM). Cancer control endpoints included biochemical failure and development of distant metastases. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS). Survival curves were calculated using Kaplan--Meier actuarial methods and compared using log-rank tests. Cox regression multivariate analyses were used to test the effect of multiple variables on treatment outcomes. Results A total of 902 patients were identified, with a median follow- up of 91 months. Of these, 390 received brachytherapy and 512 received combination therapy with EBRT. In patients with one intermediate-risk factor, the addition of EBRT did not significantly affect freedom from biochemical failure or distant metastases. Among patients with two or three intermediate-risk factors, added EBRT did not improve freedom from biochemical failure. Significant differences in late toxicity between patients treated with brachytherapy vs combination brachytherapy and EBRT were identified including urge incontinence (P < 0.001), haematuria (P < 0.001), dysuria (P < 0.001), and change in quality-of-life IPSS (P = 0.002). These symptoms were reported by patients at any point during treatment follow-up. Analysis of patients who were potent before treatment using actuarial methods showed that patients receiving combination therapy more frequently experienced loss of potency, as measured by the Mount Sinai erectile function scale (P = 0.040). Conclusion Brachytherapy monotherapy results in equal biochemical and distant control in both patients with one and more than one intermediate-risk features. While no significant benefit was shown, we believe that the addition of EBRT may prevent recurrence in patients with multiple intermediate-risk features and should be considered. [ABSTRACT FROM AUTHOR]

Objective To examine biochemical control, survival, and late morbidity with definitive low-dose-rate brachytherapy (LDR-BT) for patients with prostate cancer surviving for >10 years after treatment. Patients and Methods We identified 757 men with localised prostate cancer who underwent definitive LDR-BT in the period 1990-2006 and were followed for >10 years at our institution. Biochemical failure-free survival (BFFS), distant metastases-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were selected as study endpoints. Survival was examined using the log-rank test, Kaplan-Meier method, and Cox regression modelling. Urinary, quality of life (QoL), and potency scores at baseline and last follow-up were recorded. Results The median follow-up was 12.5 years (range, 10.1-21.8 years). At the time of analysis, 88.6% of patients were alive, 1.5% died from prostate cancer and 13.9% developed biochemical failure, with 82% of failures occurring in the first decade of follow-up. Overall, 2.3% developed distant metastases. On multivariate analyses, stage T3a-T3b, prostate-specific antigen level of >20 ng/mL, intermediate- and high-risk disease predicted worse BFFS; whereas age >70 years at diagnosis and stage T3a-T3b predicted worse OS. A total biologically effective dose of ≥150 Gy and androgen-deprivation therapy were associated with improved BFFS, but not OS. The overall 17-year rates for BFFS, DMFS, PCSS, and OS were 79, 97, 97, and 72%, respectively. Respective 17-year BFFS rates for low-, intermediate- and high-risk patients were 86, 80, and 65% (P < 0.001), whereas OS rates for the same groups were 82, 73, and 60%, respectively (P = 0.09). Amongst those patients who were potent at baseline, 25% remained potent at the last follow-up. Urinary function and QoL were mainly unaffected. Conclusions LDR-BT yields excellent survival rates, with a 17-year PCSS rate of 97%. In all, 18% of patients with biochemical relapse failed at >10 years after implantation, which justifies their continued follow-up. [ABSTRACT FROM AUTHOR]

Herein, the authors compare morbidity in men who underwent both transrectal ultrasound-guided (TRUS) prostate biopsy and transperineal mapping biopsy (TPMB) at two institutions with extensive experience in both procedures. We also identified strategies and predictive factors to reduce morbidity for both procedures. In our study, 379 men from two institutions, of which 265 (69.9%) had a prior TRUS-guided biopsy, also had TPMB performed via a template with biopsies taken at 5-mm intervals. Men in the TRUS group had a median of 12 cores sampled whereas the TPMB group had 51.5 (range, 16-151). The median biopsy density was 1.1 core/cc prostate volume. Median age and prostate-specific antigen (PSA) level were 65 years (range, 34-86) and 5.5 ng/mL (range, 0.02-118). Of these men, 11 of 265 (4.2%) who had TRUS biopsy developed urinary tract infection compared with 3 of 379 (0.79%) of those with mapping biopsy. Infection was 14.8% in TRUS biopsy group with 13 or more cores versus 2.9% in those with 12 or less (OR, 5.8; 95% CI, 1.6-21.2; P = 0.003). No men developed retention after TRUS biopsy whereas 30 of 379 (7.9%) did following TPMB. Older age, larger prostate volume (PV), and higher core number were associated with retention. On linear regression only age (P = 0.010) and PV (P = 0.016) remained as significant associations. Men older than 65 years had 12.8% versus 3.9% (OR, 3.7; 95% CI, 1.6-8.4, P= 0.001) and PV greater than 42 cc had 13.4% versus 2.7% (OR, 5.7; 95% CI, 2.1-15.1) retention incidence. In the present study TPMB is rarely associated with infection (0.78%) but more commonly with urinary retention (7.9%). Men older than 65 years and with PV greater than 42 cc were at four to five times greater retention risk. Consideration should be given to discharging these men with a urinary catheter following TPMB. [ABSTRACT FROM AUTHOR]

Objective: To increase the likelihood of detecting anterior cancers within the prostate and provide a specimen that spans the length of the gland. Newly designed 17- and 15-gauge (G) biopsy needles, a variable actuator, and an integrated pathology system intended for the longer cores were developed and tested for this purpose.Materials and Methods: Testing was performed comparing 2 common cannula tip grinds, a Vet-point (sharp tip) and a Menghini-point (atraumatic tip), and were tested against 18-G Bard Monopty in porcine kidney. A variable actuator was developed to fire the needle 20-60 mm and tested in cadaver prostates.Results: The aggregate firings for 3 different shot lengths comparing the Vet- with the Menghini-tip cannulas demonstrated 91% vs 85.2% fill (length of specimen/length of core bed, P = .007). A 15-G trocar needle with the Vet-tip cannula also had the best performance, with an aggregate standard deviation of 6.4% across 3 firing ranges and a minimum to maximum specimen length of 81%-105% of potential fill. Cadaver testing with the Vet-tip needles in the actuator for the transrectal (17-G) and transperineal (15-G) biopsies demonstrated mean fills of 93.3% and 76.5%, respectively. The new transrectal ultrasound needle obtained a 2-fold increase in specimen length over the standard Bard device (P <.001).Conclusion: Longer and consistent cores were obtained using the new biopsy needles. Combined with an adjustable actuator, the physician can obtain specimens that include peripheral and anterior zone tissue in 1 core. Determination of cancer location on the longer specimens could enhance focal therapy planning. [ABSTRACT FROM AUTHOR]

Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy. Androgen suppression combined with elective nodal and dose escalated radiation therapy (the ASCENDE-RT Trial): an analysis of survival endpoints for a randomized trial comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost for high- and intermediate-risk prostate cancer. Editorial Comment to Local dose (biological effective dose <180 Gy2) is an important predictor of biochemical recurrence in patients undergoing low-dose-rate brachytherapy. [Extracted from the article]

Objectives To describe the diagnosis of local failure after prostate brachytherapy (BT) and treatment options when recurrence is present. Methods and Materials Review of literature for local recurrence after prostate BT and salvage therapy was performed. A total of 6 patients with prostate-specific antigen increase were identified as local failures by transperineal mapping biopsy (TPMB) and treated with targeted focused therapy using cryoablation. Results Local recurrence after prostate BT occurs in 2–20% and is dose dependent. The biologic effective dose greater than 200 Gy 2 is associated with a less than 2% recurrence rate. Confirmatory biopsy should include both the prostate and seminal vesicles, as prostate cancer can be found in 20% of the latter. The pathologist should be experienced in evaluating post-irradiation tissue because of the difficulty in distinguishing benign irradiated prostate from residual or recurrent tumor. Whole gland salvage, whether by prostatectomy or cryoablation, is associated with high complication rates. Focal therapy has fewer complications but accurate targeting remains a concern. Newer diagnostic and targeting modalities such as multiparametric MRI and TPMB offer improved opportunity to increase lesion identification and ablation. A TPMB approach, which incorporates new biopsy needle design and interactive targeting software, may offer the best avenue to true focused therapy. Conclusion Local recurrences after prostate BT are uncommon because of high delivered radiation dose. When present, improved lesion identification and targeting may be associated with better cancer control and lower morbidity. [ABSTRACT FROM AUTHOR]

Prostate cancer is often associated with metastases to bone and/or soft tissue. The progression to metastatic castrate-resistant prostate cancer is a seminal event in disease progression affecting treatment decisions. A multidisciplinary group was convened to review the currently available imaging guidelines for metastatic disease in prostate cancer and found no consensus on eligibility criteria, type of imaging modality, and the frequency of scanning for detecting metastatic disease. The aim of this review was to present the recommendations from the group to identify optimal strategies for early identification of metastases in patients with prostate cancer. [Copyright &y& Elsevier]

Objectives To compare the relative importance of radiation dose escalation vs androgen deprivation therapy ( ADT) in the definitive treatment of prostate adenocarcinoma., Patients and Methods In total, 2427 patients with prostate adenocarcinoma were treated with definitive brachytherapy or brachytherapy with external beam radiation with or without ADT., Over the 20-year period of the present study (median follow-up of 78 months), patients were treated with a range of doses that were converted to the biological effective dose ( BED) and/or ADT as the treatment paradigms were optimized., Using univariate and multivariate analysis, the relative impact on the biochemical control and post-treatment prostate biopsy results of BED vs ADT was determined., Results The 10-year freedom from biochemical failure ( FBF) was significantly affected by BED group: ≤150 Gy2 (64%), >150-200 Gy2 (88%), >200-220 Gy2 (89%) and >220 Gy2 (89.5%) ( P < 0.001)., When stratified into dose groups, ADT improved FPF on multivariate analysis for the BED group (<150 Gy2, hazard ratio = 0.55; >150-200 Gy2, hazard ratio = 0.39) but not for the higher BED groups., Among patients receiving ADT, a significant difference in 10-year FBF was seen when stratifying BED into groups ≤150 Gy2 (78%) vs >150 Gy2 (87%) ( P = 0.01)., On logistic regression, ADT had a significant impact on obtaining a negative biopsy (hazard ratio = 0.21) with BED <200 Gy2, although there was no difference with BED >200 Gy2., Conclusions When treated with brachytherapy with or without EBT, ADT improves FBF only in the setting of lower doses., The benefit of ADT may be primarily as an enhancer of local control, explaining why high radiation doses can compensate for its absence. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Previous descriptions of haematuria after brachytherapy are limited., This study characterizes the long-term incidence and associated clinical risk factors of haematuria after prostate brachytherapy., Objective To characterize the incidence and clinical history of gross haematuria after prostate brachytherapy., To identify treatment risk factors for the development of gross haematuria in this setting., Patients and Methods We reviewed haematuria outcomes collected prospectively in 2454 patients treated with transperineal prostate brachytherapy over a 20-year period at a single institution., Patients were followed for a median of 5.9 years., The association of haematuria with age, pretreatment PSA, ethnicity, clinical tumour stage, Gleason score, prostate volume, isotope (iodine 125 or palladium 103), biologically effective dose ( BED), external beam radiation, androgen deprivation, development of urinary retention and occurrence of biochemical failure was investigated., Results A total of 218 men (8.9%) reported gross haematuria at a median time of 772.2 days after implantation., Haematuria was associated with prostate volume >40 cm3 ( P < 0.01), use of external beam radiation ( P < 0.01), Gleason score >7 ( P = 0.037), Asian ethnicity ( P < 0.001), BED >200 Gy ( P = 0.01), and freedom from biochemical failure ( P = 0.004)., On multivariate analysis, prostate volume >40 cm3 ( P = 0.002), external beam radiation, ( P = 0.001), and freedom from biochemical failure ( P = 0.035) were predictors of haematuria., Conclusions Late gross haematuria was observed in a small proportion of men after brachytherapy and may occur with considerable latency., Larger prostate glands, freedom from biochemical failure and external beam radiation are risk factors. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine the outcomes of prostate seed implantation in men with prostate volume (PV) of 100cc or greater (PV100). Methods: A total of 2051 men with localized prostate cancer were treated with permanent prostate brachytherapy of whom 34 (1.7%) had PV100 (mean, 126.2; range, 100–205cc). The PV100 patients were older (mean, 69 vs. 66 years; p =0.031), had higher initial prostate-specific antigen level (20.4 vs. 9.6 ng/mL, p <0.001), and received a lower dose (182 vs. 194Gy2 biologic equivalent dose, p =0.032). There were no differences in clinical stage, Gleason score, and baseline International Prostate Symptom Score. The mean followup time was 6.7 years (range, 2–18). Biochemical freedom from failure (bFFF) was defined using the Phoenix definition. Results: The BFFF at 10 years was no different between PV100 and smaller glands (82.4% vs. 84.5%, p =0.71). At last followup, mean International Prostate Symptom Score for PV100 increased from 8.5 to 9.1 against 7.4 to 9.2 for smaller glands (p =0.935). Urinary retention rates were higher for PV100 (6/34, 17.6% vs. 148/2017, 7.3%; odds ratio, 2.71; 95% confidence interval, 1.1–6.6; p =0.038). Postimplant transurethral resection of the prostate was performed in none of the 34 patients with PV100 against 66 of the 2017 patients (3.3%, p <0.001). Long-term radiation proctitis for PV100 were 1 of 34 (2.9%) against 82 of 2017 (4.1%, p =0.741). Rectourethral fistula occurred in 4 patients (0.19%), that is, 1 of 34 (2.9%) in PV100 group and 3 of 2017 (0.1%, p <0.001). Conclusion: This study demonstrates the feasibility of implanting patients with PV100. Very large PV does not influence bFFF. Although urinary retention rates were higher, the long-term urinary symptoms were no different between the two groups. Requirement for transurethral resection of the prostate was no higher in patients with PV100. Radiation proctitis rates were similar for both. [Copyright &y& Elsevier]

What's known on the subject? and What does the study add? There appears to be a clear difference in cancer control outcomes for patients with Gleason scores of 3+4 and those with scores of 4+3 after radical prostatectomy. It has been documented that patients with Gleason 4+3 prostate cancer have higher incidences of non-organ-confined disease than those with primary pattern 3. Higher rates of extracapsular extension, seminal vesicle invasion and positive margins have been found to be associated with primary pattern 4 over 3. These higher rates of non-organ-confined disease can lead to increased biochemical failure, which, in turn, can lead to higher mortality rates. This study provides information on the prognostic significance of primary Gleason pattern in the brachytherapy management of prostate cancer. Study Type - Prognosis (case series) Level of Evidence 4 OBJECTIVES To report the biochemical outcomes for Gleason 7 prostate cancer treated with brachytherapy., To analyse the impact of the primary Gleason pattern as well as other disease- and treatment-related factors on outcome., PATIENTS AND METHODS A total of 560 patients with Gleason 7 prostate cancer were treated between 1990 and 2008 with brachytherapy, alone or in combination with hormonal therapy and/or external beam radiation therapy., There were 352 patients with Gleason pattern 3+4 and 208 with Gleason pattern 4+3., The mean (range) presenting PSA level was 11.2 (1-300) ng/mL, and the median was 7.8 ng/mL., The presenting clinical stages were T1b in 1%, T1c in 33%, T2a in 16%, T2b in 32%, T2c in 16% and T3 in 2% of patients., RESULTS The actuarial freedom from biochemical failure rate at 10 years was 82%., There was no significant difference between 10-year freedom from biochemical failure rates for patients with Gleason scores of 3+4 (79%) and those with scores of 4+3 (82%)., Biologically effective dose and presenting PSA level were both significant predictors of biochemical failure in multivariate analysis., CONCLUSIONS The primary Gleason pattern in Gleason 7 prostate cancer shows no significant effect on biochemical failure when treated with brachytherapy., These results are different from those found after radical prostatectomy and are probably attributable to the enhanced local control afforded by a brachytherapy approach to this disease subset. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To describe the technique and outcomes of seminal vesicle biopsy (SVB) and permanent implantation in patients with T3b prostate cancer. Methods and Materials: Intermediate- and high-risk prostate cancer patients who elected brachytherapy as their treatment of choice were offered SVB for either Gleason score ≥7, prostate-specific antigen levels >10ng/mL, or clinical stage ≥T2b. Three cores were taken from both seminal vesicles at the base of the prostate using transrectal ultrasound. Patients with a positive SVB and either a negative pelvic lymph node dissection or pelvic computerized tomogram were treated with a combination of a partial implant followed by 45Gy of external beam irradiation therapy. During the seed implant, sources were positioned in the anterior wall of the seminal vesicles using intraoperative dosimetry to guide placement. Biochemical freedom from failure was determined using a definition of >0.2ng/mL. Survival was measured using the Kaplan–Meier and Cox proportions projections. Results: Of 526 patients who underwent SVB, 52 (9.9%) were positive for prostate cancer invasion. Clinical stage, prostate-specific antigen levels, and Gleason score were all predictive of a positive SVB (p <0.001). The 10-year biochemical freedom from failure was 64%. Cox regression demonstrated Gleason score (p =0.044) and biologic effective dose (p =0.013) as significant. Conclusions: Patients with pathologically confirmed seminal vesicle involvement of prostate cancer can be successfully identified and managed by a combined approach of permanent seed implantation to the prostate and seminal vesicles followed by external beam irradiation therapy. SVB should be encouraged in men with high-risk prostate cancer and aggressively treated when encountered. [Copyright &y& Elsevier]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Previously, rates of potency preservation with or without external beam radiation and/ or hormone therapy have been published with smaller series and limited follow-up. The study provides greater numbers and longer follow-up giving patients and clinicians a better appreciation of the true potency preservation rates in this population and how various factors such as age, hormone use and external beam affect those rates. OBJECTIVES To assess potency preservation in men following brachytherapy for prostate cancer with or without external beam radiation therapy (EBRT) and/or androgen deprivation therapy (ADT)., To evaluate the factors that significantly impact this rate., PATIENTS AND METHODS In all, 1063 potent men with T1-T3 prostate cancer were treated from 1990 to 2007 with seed implantation alone (103Pd or 125I) (69.6%) or combined modality treatment consisting of a partial dose 103Pd implant followed 6-8 weeks later by EBRT (45 Gy, prostate/seminal vesicles only) (30.4%). ADT was used in 49.1% of cases (range 1-27 months)., Patients were required to have a minimum of 2 years follow-up and to be off ADT for a minimum of 1 year., Erectile function was assessed prior to seed implantation and at each follow-up visit using the physician-assigned Mount Sinai Erectile Function Score (MSEFS): 0, unable to have erections; 1, erections insufficient for intercourse; 2, suboptimal erections but sufficient for intercourse; 3, normal erectile function. Potent was defined as a score of greater than or equal to 2 with or without use of a phosphodiesterase type 5 inhibitor., The potency rate was calculated using actuarial methods with comparisons tested by log-rank and Cox regression analysis., RESULTS The 5-year and 10-year actuarial rate of potency preservation was 68.0% and 57.9%, respectively, at last follow-up., On multivariate analysis, 5- and 10-year potency was 87.6% (79.5%) for men younger than 60, 68.0% (57.5%) for age 60-70, and 42.2% (31.0%) for men older than 70 ( P < 0.001)., Pretreatment MSEFS of 2 had a potency rate of 51.7% (37.2%) vs 74.2% (65.2%) for an MSEFS of 3 ( P < 0.001)., There was a 75.8% (62.6%) potency rate without ADT vs 60.0% (53.0%) with ADT ( P < 0.001)., Five-year potency was 76.4% for implant alone, 71.0% for implant with EBRT, 62.2% for implant with ADT, and 57.9% for implant with EBRT and ADT ( P < 0.001)., CONCLUSION Increasing initial age at implant, diminished pretreatment erectile function and the use of combination therapy with EBRT and/or ADT significantly increases erectile dysfunction following brachytherapy. [ABSTRACT FROM AUTHOR]

Purpose: Because limited information exists regarding whether the rate or magnitude of PSA decline following brachytherapy predicts long-term clinical outcomes, we evaluated whether achieving a prostate-specific antigen (PSA) nadir (nPSA) <0.5 ng/mL following brachytherapy is associated with decreased PSA failure and/or distant metastasis. Methods and Materials: We retrospectively analyzed our database of early-stage prostate adenocarcinoma patients who underwent brachytherapy, excluding those receiving androgen-deprivation therapy and those with <2 years follow-up. Median and mean pretreatment PSA were 6 ng/mL and 7.16 ng/mL, respectively. By clinical stage, 775 were low risk (≤T2a), 126 were intermediate risk (T2b), and 20 were high risk (>T2b). By Gleason score, 840 were low risk (≤6), 71 were intermediate risk (7), and 10 were high risk (>7). Patients were treated with brachytherapy only (I-125, n = 779, or Pd-103, n = 47), or brachytherapy + external-beam radiation therapy (n = 95). Median follow-up was 6.3 years. We noted whether nPSA <0.5 ng/mL was achieved and the time to achieve this nadir and tested for associations with pretreatment risk factors. We also determined whether this PSA endpoint was associated with decreased PSA failure or distant metastasis. Results: Absence of high-risk factors in clinical stage (≤T2b), Gleason score (≤7), and pretreatment PSA (≤20 ng/mL) was significantly associated with achieving nPSA <0.5 ng/mL. By Kaplan-Meier analysis, patients achieving nPSA <0.5 ng/mL had significantly higher long-term freedom from biochemical failure (FFBF) than nonresponders (5-year FFBF: 95.2 ± 0.8% vs. 71.5 ± 6.7%; p < 0.0005). Among responders, those who achieved nPSA <0.5 ng/mL in ≤5 years had higher FFBF than those requiring >5 years (5-year FFBF: 96.7 ± 0.7% vs. 80.8 ± 4.6%; p < 0.0005). On multivariate analysis, patients who achieved nPSA <0.5 ng/mL in ≤5 years had significantly higher FFBF than other patients. Conclusions: Pretreatment risk factors (clinical tumor stage, Gleason score, pretreatment PSA) strongly predict for patients achieving nPSA <0.5 ng/mL following brachytherapy, and this cohort had significantly higher long-term FFBF. [Copyright &y& Elsevier]

Purpose: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Methods and Materials: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with 103Pd or 125I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Results: Median follow-up was 86 months (range, 2–156). The median dose to 90% of the prostate volume was 122 Gy (range, 67–166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade ≥2 toxicity (p = 0.03). Conclusion: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity. [Copyright &y& Elsevier]

Abstract: Purpose: To investigate the morbidity of higher radiation doses in prostate cancer patients. Methods and Materials: Five hundred eighty-five men treated with seed implantation and external beam irradiation were followed a median of 5 years (range, 2–11). Hormonal therapy (HT) of 9 months duration was used in 504 (86.2%) patients. The biologic effective dose (BED) was calculated using an α/β of 2. Urinary incontinence (UI) and symptoms (IPSS) were prospectively collected. Rectal morbidity was scored according to the Radiation Therapy Oncology Group (RTOG) scale. Two BED dose groups of ≤220Gy (n =449) and >220Gy (n =136) were used. Comparisons of means were made by Student''s t test, and the associations were tested by chi-square analysis (Pearson). Results: Urinary retention developed in 36 (6.2%) and was not associated with BED or IPSS. Retention occurred more often with prostate volume >50cc (17%, p =0.001). The median change in urinary symptoms (IPSS) was 1. Sixty-one percent with high BED were more likely to have increased postimplant symptoms compared with 39% with lower BED (p =0.025; odds ratio [OR], 1.107; 95% confidence interval [CI], 1.10–1.21). UI occurred in 25 patients (4.3%) and was only associated with a postimplant transurethral resection of the prostate (TURP) (n =25), 16% vs. 2.3% for no TURP (p =0.001; OR, 8; 95% CI, 2.4–27). Of the 373 patients initially potent, 204 (54.7%) maintained potency. Impotence was only associated with age at implant (p =0.001) and HT (p =0.004). Sixty-two (10.6%) patients had Grade 1–2 and 4 patients had Grade 3–4 (0.7%, 2 ulcers and 2 fistulas) rectal complications. Three of the Grade 3/4 complications occurred with a dose ≤220Gy. Conclusion: A BED >220Gy does not seem to increase morbidity. [Copyright &y& Elsevier]

Purpose: To determine factors that influence local control and systemic relapse in patients undergoing permanent prostate brachytherapy (PPB). Methods and Materials: A total of 584 patients receiving PPB alone or PPB with external beam radiation therapy (19.5%) agreed to undergo prostate biopsy (PB) at 2 years postimplantion and yearly if results were positive or if the prostate-specific antigen (PSA) level increased. Short-term hormone therapy was used with 280 (47.9%) patients. Radiation doses were converted to biologically effective doses (BED) (using α/β = 2). Comparisons were made by chi-square analysis and linear regression. Survival was determined by the Kaplan-Meier method. Results: The median PSA concentration was 7.1 ng/ml, and the median follow-up period was 7.1 years. PB results were positive for 48/584 (8.2%) patients. Positive biopsy results by BED group were as follows: 22/121 (18.2%) patients received a BED of  ≤150 Gy; 15/244 (6.1%) patients received >150 to 200 Gy; and 6/193 (3.1%; p < 0.001) patients received >200 Gy. Significant associations of positive PB results by risk group were low-risk group BED (p = 0.019), intermediate-risk group hormone therapy (p = 0.011) and BED (p = 0.040), and high-risk group BED (p = 0.004). Biochemical freedom from failure rate at 7 years was 82.7%. Biochemical freedom from failure rate by PB result was 84.7% for negative results vs. 59.2% for positive results (p < 0.001). Cox regression analysis revealed significant associations with BED (p = 0.038) and PB results (p = 0.002) in low-risk patients, with BED (p = 0.003) in intermediate-risk patients, and with Gleason score (p = 0.006), PSA level (p < 0.001), and PB result (p = 0.038) in high-risk patients. Fifty-three (9.1%) patients died, of which eight deaths were due to prostate cancer. Cause-specific survival was 99.2% for negative PB results vs. 87.6% for positive PB results (p < 0.001). Conclusions: Higher radiation doses are required to achieve local control following PPB. A BED of >200 Gy with an α/β ratio of 2 yields 96.9% local control rate. Failure to establish local control impacts survival. [Copyright &y& Elsevier]

OBJECTIVE To assess the outcomes for patients with Gleason score 8–10 prostate cancer treated with brachytherapy, external beam radiotherapy (EBRT) and hormonal therapy (HT). PATIENTS AND METHODS In all, 181 patients with Gleason scores 8–10 prostate cancer were treated from 1994 to 2006 with a 103Pd implant (prescription dose 100 Gy), 45 Gy of EBRT and 9 months of HT. The median (range) follow-up was 65 (24–150) months; freedom from biochemical failure (FBF) rates were calculated using the Phoenix definition. RESULTS The 8-year actuarial FBF, freedom from distant metastases, prostate-cancer specific survival and overall survival were 73%, 80%, 87% and 79%, respectively. The pretreatment prostate-specific antigen (PSA) level significantly affected FBF, with 8-year rates of 72%, 82% and 58% for patients with PSA level of ≤10, >10–20 and >20 ng/mL, respectively ( P = 0.006). The PSA level had no significant effect on rates of distant metastases. The Gleason score had the most significant affect on FBF in a multivariate analysis, and was the only factor to significantly affect rates of distant metastases; the 8-year FBF rates were 84%, 55% and 30% for scores of 8, 9 and 10, respectively ( P = 0.003). The corresponding freedom from distant metastases and prostate-cancer specific survival rates were 86%, 76%, 30% ( P < 0.001) and 92%, 80%, 62.5% ( P = 0.003), respectively. CONCLUSIONS The 8-year outcomes after this regimen showed favourable biochemical and distant control, as well disease-specific survival rates for patients with Gleason scores of 8–10. This treatment approach should be considered as a viable option for this subset of patients with high-risk disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the biochemical control rates and survival for Gleason score 7–10 prostate cancer patients undergoing permanent prostate brachytherapy as a function of the biologic effective dose (BED). Methods and Materials: Six centers provided data on 5,889 permanent prostate brachytherapy patients, of whom 1,078 had Gleason score 7 (n = 845) or Gleason score 8–10 (n = 233) prostate cancer and postimplant dosimetry results available. The median prostate-specific antigen level was 7.5 ng/mL (range, 0.4–300). The median follow-up for censored patients was 46 months (range, 5–130). Short-term hormonal therapy (median duration, 3.9 months) was used in 666 patients (61.8%) and supplemental external beam radiotherapy (EBRT) in 620 (57.5%). The patients were stratified into three BED groups: <200 Gy (n = 645), 200–220 Gy (n = 199), and >220 Gy (n = 234). Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. Results: The 5-year bFFF rate was 80%. The bFFF rate stratified by the three BED groups was 76.4%, 83.5%, and 88.3% (p < 0.001), respectively. Cox regression analysis revealed Gleason score, prostate-specific antigen level, use of hormonal therapy, EBRT, and BED were associated with bFFF (p < 0.001). Freedom from metastasis improved from 92% to 99% with the greatest doses. The overall survival rate at 5 years for the three BED groups for Gleason score 8–10 cancer was 86.6%, 89.4%, and 94.6%, respectively (p = 0.048). Conclusion: These data suggest that permanent prostate brachytherapy combined with EBRT and hormonal therapy yields excellent bFFF and survival results in Gleason score 7–10 patients when the delivered BEDs are >220 Gy. These doses can be achieved by a combination of 45-Gy EBRT with a minimal dose received by 90% of the target volume of 120 Gy of 103Pd or 130 Gy of 125I. [Copyright &y& Elsevier]

Purpose: The purpose of this study was to characterize the oncologic results and toxicity profile of patients treated with 125I implants using the dose delivered to 90% of the gland from the dose–volume histogram (D90) of greater than 144 Gy. Methods and Materials: From June 1995 to Feb 2005, a total of 643 patients were treated with 125I monotherapy for T1–T2 prostate cancer with a D90 of 180 Gy or greater (median, 197 Gy; range, 180–267 Gy). Implantations were performed using a real-time ultrasound-guided seed-placement method and intraoperative dosimetry to optimize target coverage and homogeneity by using modified peripheral loading. We analyzed biochemical disease-free survival (bDFS) of 435 patients who had a minimum 2-year prostate-specific antigen follow-up (median follow-up, 6.7 years; range, 2.0–11.1 years). Results: Five-year bDFS rates for the entire cohort using the American Society for Therapeutic Radiology and Oncology and Phoenix definitions were 96.9% and 96.5%, respectively. Using the Phoenix definition, 5-year bDFS rates were 97.3% for low-risk patients and 92.8% for intermediate/high-risk patients. The positive biopsy rate was 4.1%. The freedom rate from Grade 2 or higher rectal bleeding at 5 years was 88.5%. Acute urinary retention occurred in 10.7%, more commonly in patients with high pretreatment International Prostate Symptom Scores (p < 0.01). In patients who were potent before treatment, 73.4% remained potent at 5 years after implantation. Conclusions: Patients with a minimum D90 of 180 Gy had outstanding local control based on prostate-specific antigen control and biopsy data. Toxicity profiles, particularly for long-term urinary and sexual function, were excellent and showed that D90 doses of 180 Gy or greater performed using the technique described were feasible and tolerable. [Copyright &y& Elsevier]

Purpose: To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group. Methods and Materials: Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. 125I was used in 2,293 (58%), 103Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140–200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log–rank test. Results: The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). Conclusions: These data suggest that permanent brachytherapy dose prescriptions can be customized to risk status. In low-risk patients, achieving a BED of ≥140 Gy might be adequate for prostate-specific antigen control. However, high-risk disease might require a BED dose of ≥200 Gy. [Copyright &y& Elsevier]

Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. Largely due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. The reason that brachytherapy results are reproducible in several different practice settings is because numerous implant quality factors have been defined over the last 20 years, which can be applied objectively to judge the success of the intervention both during and after the procedure. In addition, recent long-term follow-up studies have clarified that the secondary cancer incidence of brachytherapy is not clinically meaningful. In terms of future directions, the study of radiation repair genetics may allow for the counseling physician to better estimate any given patients risk for side effects, thereby substantially reducing the therapeutic uncertainties faced by patients choosing a prostate cancer intervention. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the effect of low-dose rate prostate brachytherapy on the sexual health of men with ≥ 7 years of prospective evaluation and optimum sexual function before treatment. PATIENTS AND METHODS In all, 223 patients with T1b to T3a prostate cancer and a median (range) age of 66 (50–82) years were treated with permanent seed implantation from November 1990 to March 1998. They were followed for a median (range) of 8.2 (7–14.1) years using prospective quality-of-life measures. Erectile function (EF) was assessed using a physician-assigned score and beginning in June 2000; the validated International Index of EF (IIEF-5) was used as a complementary method to quantify late EF. No adjustment was made to differentiate sexual function with or with no pharmacological intervention for EF. Pearson’s chi-square test and Student’s t-test were used to compare the groups. RESULTS Of the 223 men, 131 (59%) had optimal EF before their brachytherapy; of these, 51 (40%) at the last follow-up evaluation were using either a phosphodiesterase type 5 inhibitor (44, 86%), yohimbine (two, 4%) or alprostadil (five, 10%). The age at implantation was highly predictive of current EF; 23 of 25 (92%) men aged 50–59 years had a current EF of ≥ 2; those aged 60–69 and 70–78 years had an EF of ≥2 in 48/75 (64%) and 18/31 (58%) ( P = 0.01). A current IIEF-5 score of ≥ 16 also correlated highly with age at implant, i.e. 50–59, 16/25 (64%); 60–69, 20/75 (27%) and 70–78 years, 6/31 (19%) ( P < 0.001). CONCLUSION Patients aged <60 years and with optimal EF before low-dose rate prostate brachytherapy have a very high probability of long-term EF. [ABSTRACT FROM AUTHOR]

Purpose: We describe biopsy results in patients with prostate cancer treated with brachytherapy. Materials and Methods: A total of 1,562 men with localized prostate cancer were treated with permanent prostate brachytherapy, of whom 508 agreed to ultrasound guided biopsies 2 years after the completion of all therapy. Median followup was 6.7 years (range 2 to 14.6) and median prostate specific antigen was 7.4 ng/ml (range 0.3 to 300). Disease was categorized as Gleason score less than 7 in 74.8% of patients, stage T2a or less in 64.2%, low risk in 43.1%, intermediate risk in 24.2% and high risk in 32.7%. Of the 508 men 315 (62%) received 125I, 110 (21.7%) received 103Pd and 83 (16.3%) received 103Pd and external beam radiotherapy. A total of 237 men (46.7%) received a short course of hormonal therapy (3 to 9 months). Subsequent biopsies were performed after 2 years if initial biopsy was positive or prostate specific antigen increased. Post-implantation dosimetry results were grouped into low, normal and high dose. Associations were tested by chi-square analysis. Survival functions were calculated with Kaplan-Meier analysis and Cox regression. Results: A total of 643 biopsies were performed in 508 men between 2 and 11 years after implantation. Of the 508 men 39 (7.7%) had a final positive biopsy. Positive biopsy was associated with high prostate specific antigen (p = 0.035), stage (p = 0.003), risk (p = 0.024), no hormonal therapy (p = 0.002) and low dose (p <0.0001). On multivariate analysis only dose and hormonal therapy were significant (p <0.0001 and p = 0.004, respectively). Of the patients 80% were free of PSA failure at 10 years if final biopsy was negative compared to 27.3% with a positive biopsy (p <0.0001). Death from prostate cancer was associated with a positive biopsy (OR 18.5, 95% CI 2.3–143, p <0.0001). Of the 52 men with a positive biopsy at year 2, 23 (44.2%) had negative results on subsequent biopsy, while 10 of the 456 (2.2%) with negative 2-year biopsies showed positive results. Positive biopsy occurred in the prostate only in 31 of 39 men (79.5%), in the prostate and seminal vesicles in 3 (7.7%), and in the seminal vesicles only in 5 (12.8%). Conclusions: Patients undergoing prostate brachytherapy must receive an adequate radiation dose to eradicate local disease. Hormonal therapy may benefit local control in patients with intermediate to high risk disease. Extraprostatic biopsies should be performed in patients with local failure who are considering salvage therapy to rule out seminal vesicle involvement. [Copyright &y& Elsevier]

Purpose: We describe the effects of prostate brachytherapy with or without hormonal therapy, or external beam irradiation on gland volume. Materials and Methods: A total of 600 men with localized prostate cancer underwent 125I (357), 103Pd (118) or partial 103Pd combined with external beam irradiation (125) brachytherapy. Of the 600 men 299 (49.8%) received 3 to 9 months of hormonal therapy, which was initiated 3 months before implantation. Hormonal therapy consisted of luteinizing hormone-releasing hormone agonist plus antiandrogen in 251, luteinizing hormone-releasing hormone agonist in 41 and flutamide plus finasteride in 7. Prostate volume measurements were made before the initiation of hormonal therapy, at implantation and yearly. Median followup was 5.2 years. Associations were tested by chi-square analysis. Means were compared by 1-way ANOVA and the Student t test. Results: Median initial prostate volume was 38.5 cc (range 9.2 to 151.5). Pre-implantation hormonal therapy resulted in a median prostate volume decrease of 33.1%. The mean reduction for luteinizing hormone-releasing hormone agonist was 27.6%, for luteinizing hormone-releasing hormone agonist plus antiandrogen it was 32.8% and for flutamide plus finasteride it was 10.8% (p = 0.003). Prostate volume decreased 36.6% by year 1, 42.4% by year 4, 45.6% by year 6 and 51.2% by year 8 (p <0.0001). There was no difference in prostate volume reduction at year 1 between men receiving hormonal therapy vs implantation alone. Patients treated with 103Pd had a greater prostate volume reduction at 1 year than those who received 125I (p = 0.004). Conversely patients treated with hormonal therapy and 125I had a smaller prostate volume reduction than those implanted with 125I alone (p = 0.023). After year 1 there were no longer differences between any groups. Conclusions: Luteinizing hormone-releasing hormone agonist plus antiandrogen is more successful for reducing prostate volume before prostate brachytherapy than luteinizing hormone-releasing hormone agonist or flutamide plus finasteride. Hormonal therapy offered no advantage over implantation alone for post-implantation prostate volume reduction. 103Pd appears to reduce prostate volume more rapidly than 125I but this advantage is lost by year 2. No rebound in prostate volume was noted at longer followup. [Copyright &y& Elsevier]

Objectives: To define the long-term morbidity in patients with prostate cancer who underwent iodine-125 brachytherapy. Methods: A total of 325 men with localized prostate cancer treated with iodine-125 brachytherapy had a median follow-up of 7 years (range 5 to 15). The American Urological Association symptom score, erectile function status, rectal bleeding incidence, and presence of urinary incontinence were collected prospectively before implantation and every 6 months thereafter. Comparisons were made between the pretreatment and treatment-related factors and their associations with quality-of-life changes. Associations were tested using the Student t, chi-square, and Wilcoxon signed rank tests. Results: The median prostate volume and maximal dose to 90% of the prostate was 36.6 cm3 and 167 Gy, respectively. Of the 325 men, 15.7% experienced prostate-specific antigen failure and 4% started androgen deprivation therapy. The mean total symptom and bother scores increased from baseline (P <0.001) to 6 months after implantation, steadily decreased, and were unchanged at the last follow-up visit (P = 0.6). There were no significant associations among patient age, race, hormonal therapy use, prostate size, radiation dose, and urinary morbidity. Incontinence occurred in 4 (1.2%) of the 325 patients at the last follow-up visit and was associated with transurethral resection of the prostate (odds ratio 8.8, 95% confidence interval 1.3 to 62, P = 0.008). Before implantation, 77.2% were able to have an erection adequate for intercourse and 50.6% were able to at the last follow-up visit. A significant correlation was found between potency preservation and age (P <0.001). Rectal bleeding occurred in 78 men (24%) 1 to 3 years after implantation. Nine patients (2.8%) complained of minor bleeding beyond 5 years, which was associated with greater radiation doses (P = 0.023). Conclusions: The preservation of urinary, sexual, and rectal quality of life is excellent at long follow-up for patients implanted with iodine-125. [Copyright &y& Elsevier]

Purpose: To analyze the effect of biologically effective dose (BED) values on prostate-specific antigen (PSA) failure and posttreatment biopsy. Mehods and Materials: From 1990 to 2003, 1,377 patients had prostate brachytherapy alone (I-125 or Pd-103) (571), hormonal and brachytherapy (371), and trimodality therapy (hormonal, implant, and external beam) (435). Dose was defined as the D90 (dose delivered to 90% of the gland from the dose–volume histogram). Results: Freedom from PSA failure (FFPF) at 10 years was 87%. The 10-year FFPF for BED <100, >100–120, >120–140, >140–160, <160–180, >180–200, and >200 were 46%, 68%, 81%, 85.5%, 90%, 90%, and 92%, respectively (p < 0.0001). BED and Gleason score had the greatest effect, with p values of p < 0.0001 in multivariate analysis. Posttreatment positive biopsy rate was 7% (31/446). The positive biopsy rates for BED ≤100, >100–120, >120–140, >140–160, >160–180, >180–200, and >200 were 24% (8/33), 15% (3/20), 6% (2/33), 6% (3/52), 7% (6/82), 1% (1/72), and 3% (4/131), respectively (p < 0.0001). BED was the most significant predictor of biopsy outcome in multivariate analysis (p = 0.006). Conclusions: Biologically effective dose equations provide a method of comparing different isotopes and combined therapies in the brachytherapy management of prostate cancer. The effects of BED on FFPF and posttreatment biopsy demonstrate a strong dose–response relationship. [Copyright &y& Elsevier]

Abstract: Objectives: To investigate a method to decrease the problem of seed migration after permanent prostate brachytherapy. Permanent prostate brachytherapy can be performed by a number of techniques using several different seed configurations. All have been associated with some degree of pulmonary seed migration, and no studies have clearly investigated a means of decreasing this problem. Methods: A total of 238 patients underwent implantation with either iodine-125 (I-125; 146 patients) or palladium-103 (92 patients). The implant was performed in real time using an applicator, with the sources placed just underneath the prostatic capsule. Postimplant dosimetry was performed at 1 month. Routine chest x-ray was obtained a minimum of 4 months after implantation; 24 patients had a second chest x-ray taken. Results: A total of 21,654 seeds were implanted (median 89, range 27 to 220). Postimplant chest x-rays were obtained at a median of 912 days (range 147 to 3023), and 4 patients (1.7%) experienced at least one seed embolus to the lung. Of the 21,654 seeds, 10 (0.005%) were found in the lungs. All 4 patients had received an I-125 implant, resulting in a pulmonary embolus rate for I-125 of 2.7% (4 of 146) and for palladium-103 of 0% (0 of 92). No patients experienced subsequent seed migration if it was not seen on the initial film. The median dose delivered to 90% of the prostate volume for all patients undergoing I-125 implantation was 172 Gy and for the 4 patients with seed migration it was 174 Gy. Conclusions: Seed embolism to the lungs is a rare event when patients undergo implantation using the real-time method. Although in our series migration was slightly greater with I-125 than with palladium-103, no negative effect was seen on the postimplant dosimetry results. [Copyright &y& Elsevier]

ABSTRACT: Purpose:: We determined the 10-year biochemical and local control results for 125I prostate brachytherapy in men followed a minimum of 4 years. Materials and Methods:: A total of 279 men with T1–T2 prostate cancer with a minimum followup of 4 years were implanted with 125I from 1990 to 1998 using the real-time technique. Patients were treated with the implant alone (215 or 72.5%) or with the implant and 6 months of hormone therapy (64 or 27.6%). Of the men 185 (66.3%) agreed to ultrasound guided biopsy (6 to 12 cores) a minimum of 2 years after implantation. All patients with increasing prostate specific antigen (PSA), evidence of local recurrence or a prior positive biopsy underwent repeat biopsy yearly until biopsy became negative or there was clear evidence of biochemical (PSA) progression. The radiation dose delivered to 90% of the gland (D90) was determined 30 days after implantation by computerized tomography based dosimetry. Biochemical failure was defined as 3 consecutive PSA increases. Survival curves were calculated by the Kaplan-Meier method. Cross tabulations were tested by Pearson chi-square analysis. The effect of multiple variables was tested by the log rank test (Cox regression). Results:: Median patient age was 67 years (range 42 to 82) and median followup was 6 years (range 4 to 12). Of the patients 49 (17.6%) experienced failure, for a 10-year freedom from failure (FFF) rate of 78%. Univariate analysis for 10-year FFF demonstrated that initial PSA (p = 0.001), stage (p = 0.002), risk group (p <0.001), hormone therapy (p = 0.013) and D90 (p <0.001) were significant. Multivariate analysis demonstrated that D90 (p <0.001) and risk group (p = 0.013) were the only significant variables. The RR of PSA failure was 3.0 (95% CI 2.0 to 4.4, p <0.001) and 5.6 (95% CI 3.1 to 10, p <0.001) for doses below 140 and 120 Gy, respectively. Of the 185 patients 166 (90%) had a negative post-implantation prostate biopsy. FFF was 85% vs 21% in those with a positive biopsy (p <0.001). Patients with a D90 of at least 140 Gy had a positive biopsy rate of 4.8% compared to 20.5% in those with a lower dose (p <0.001). The RR for positive biopsy at doses less than 140 and 120 Gy was 2.6 (95% CI 1.6 to 4.4, p = 0.002) and 4.3 (95% CI 2.3 to 8.1, p <0.001), respectively. Conclusions:: These data demonstrate high biochemical and local control in men with T1–T2 prostate cancer treated with 125I brachytherapy. The delivered radiation dose and risk category are important predictors of success. Patients receiving a dose of at least 140 Gy have a 90% chance of biochemical FFF and a 95.2% likelihood of local control. [Copyright &y& Elsevier]

To evaluate, in a retrospective review, prostate brachytherapy dosimetry outcomes relative to the transurethral resection of the prostate (TURP) cavity size to address the theoretical concern that an intraprostatic cavity may hinder adequate radioactive source placement.A total of 73 patients who underwent prostate brachytherapy as part of their treatment of localized prostate cancer had a history of a prior TURP. Of these 73 patients, 37 underwent 125I implantation, 19 103Pd implantation, and 17 partial 103Pd implantation. The dose was calculated using the dose to 90% of the prostate gland (D90) from the 1-month post-implant dosimetric analysis. The doses were normalized relative to 100% of the prescription dose. Archived transrectal ultrasound images were used to determine the maximal length and width of the visible residual TURP cavities. The prolate spheroid or symmetric egg shape was used to calculate each residual cavity volume. The derived volume of the TURP cavity was divided by the measured ultrasound volume of the prostate at brachytherapy, creating a percentage of volume measurement for each prostate. All p values, unless otherwise specified, were generated by comparing patients without a visible TURP defect with the subgroups of patients with a visible defect using the Student t test.A visible residual TURP defect was noted on the operative transrectal ultrasound images of 55 (75%) of the 73 patients with a history of TURP before brachytherapy. The 18 patients without a visible TURP defect had a median D90 of 96% and were used for subsequent statistical comparison. Thirty-six patients with a TURP defect <10% of the entire prostate volume had a median D90 of 109% (p = 0.02). Thirteen patients with a TURP defect between 10% and 20% of the prostate volume had a median D90 of 112% (p = 0.03). Six patients with a TURP defect >20% of the prostate volume had a D90 of 89% (p = 0.43).A visible residual TURP cavity that is assumed to have a prolate spheroid shape and occupy ≥10% of a prostate volume did not appear to be a statistically significant hindrance to proper dosimetric outcome. [Copyright &y& Elsevier]

: PurposeAchieving a minimal dose of 140 Gy to 90% of the prostate (D90) on postimplant dosimetry has been shown to yield improved biochemical control by 125I brachytherapy, and a D90 >180 Gy can be associated with increased long-term toxicity of seed implantation. Significant enlargement of the prostate on postimplant CT compared with the ultrasound (US) volume at implantation (CT/US ratio) has been associated with lower dose results, but other factors predicting for high or low doses are not well established. We determined whether the prostate size at implantation influenced the CT/US ratio results affecting postimplant dosimetry or predicted for D90 values <140 or >180 Gy in patients implanted with 125I in a community hospital setting.: Methods and materialsThe dosimetry results from 501 patients from 33 community hospitals were analyzed after full dose 125I implantation. Implant radioactivity was obtained from reference tables relating millicuries to prostate volume (PV). Seeds were placed under real-time US guidance with peripheral weighting in a uniform method for all prostate sizes. CT-based dosimetry was performed 1 month after implantation. Dose–volume histogram parameters were analyzed for volume effects, including D90, the dose to 10% and 30% of the rectal wall, and the dose to 30% of the urethra and bladder. The PV was defined as small (<25 cm3), medium (25 to <40 cm3), or large (≥40 cm3).: ResultsThe PV ranged from 9 to 79 cm3 (median 32.7). A D90 ≥140 Gy was achieved in 452 patients (90%). The median D90 was 164 Gy (range 90–230) and increased from 149.5 Gy in small prostates to 164 Gy in medium (p <0.001) and 176 Gy in large (p <0.001) prostates. A D90 <140 Gy occurred in 20% of small vs. 9% of medium and 3% of large prostates (p = 0.003). A D90 >180 Gy occurred in 7% of small and 10% of medium vs. 25% of large glands (p <0.001). The rectal dose increased significantly with an enlarging PV. The bladder and urethral doses increased from the small to medium PVs, although did not increase further in the large glands. The median CT/US ratios showed a significant volume relationship, decreasing with enlarging PVs, but were not associated with a D90 <140 or >140 Gy. The D90 results for <140 Gy and >140 Gy occurred at equal activities per volume.: ConclusionNinety percent of patients implanted by community-level practitioners using reference tables and real-time US-guided implantation achieved a D90 outcome of ≥140 Gy. Significant differences in dose outcomes <140 Gy and >180 Gy occurred related to PV. Those with prostates <25 cm3 had a 20% frequency of D90 <140 Gy, unrelated to excessive postimplant volume enlargement or insufficient activity per reference table, suggesting that the activity-to-volume recommendations may not allow for much variance in final seed position. Such seed displacement may contribute to lower doses, most commonly in small glands. One may consider increasing the activity implanted in small prostates, because a D90 >180 Gy occurred in only 7% of these cases. Patients with glands >40 cm3 were 25% likely to have a D90 result >180 Gy and were at only 3% risk of a D90 <140 Gy. These patients may benefit from intraoperative dosimetry or a reduction in implant activity. [Copyright &y& Elsevier]

: PurposeAlthough acute urinary morbidity after prostate brachytherapy has been well-documented, long-term effects have not been fully characterized. We describe a late complication of I-125 prostate brachytherapy we have termed urinary symptom flare.: Methods and materialsA total of 172 patients who underwent I-125 prostate brachytherapy between 1991 and 1998 completed a pretreatment and at least four follow-up International Prostate Symptom Score (IPSS) forms. Follow-up visits were made 1 month after implant and at 3- to 6-month intervals thereafter. Follow-up periods ranged from 12 to 106 months (median 41.5 months). The number of IPSS forms per patient ranged from 4 to 17 (median 6). A total of 32.6% of patients received both 3 months of neoadjuvant and 3 months of adjuvant hormonal therapy. Postimplant dosimetry revealed D90 values of 5578–25692 cGy (median 17290 cGy). The peak voiding score, indicating the time of the most severe urinary morbidity after brachytherapy, was defined as the highest rise in IPSS recorded after implantation. The nadir score was the lowest IPSS attained after the peak score, generally indicating a return to the patient’s preimplant urinary function. A “flare” was defined as a rise in IPSS from the nadir score of at least five points, denoting a late exacerbation of urinary symptoms. Patients with a transient rise in PSA of 0.1 ng/ml or greater were considered to have a PSA bounce.: ResultsThe mean pretreatment IPSS for the study population was 7.5. The mean peak IPSS was 19.4 and occurred from 0.1 to 25 months (median 1.3 months) after the date of implant. The mean nadir IPSS was 6.7 and occurred from 1.6 to 61.6 months (median 14.3) after brachytherapy. A total of 35.5% of patients (61/172) have experienced a urinary flare of 5 or more points, as measured by the IPSS form. The mean “flare” IPSS was 16.4. The time to develop a flare ranged from 5.8 to 64 months (median 23.9 months). The actuarial risk of developing a flare was 21% by 2 years, 34% by 3 years, 38% by 4 years, and 47% by five years. In 72% of patients (44/61) who developed a flare, the flare subsided to baseline by the next follow-up visit. Of the remaining patients, 3% (2/61) reached a baseline value two follow-up visits later. In 25% of the patients (15/61) who experienced a flare, it occurred during their last follow-up visit. No single factor, including PSA (p = 0.9), stage (p = 0.9), use of hormone therapy (p = 0.9), implanted activity (p = 0.1), ultrasound volume (p = 0.4), dose (p = 0.4), seed number (p = 0.4), or needle number (p = 0.9), had a significant effect on the risk of developing a flare. There was a trend for younger patients (≤65 vs. >65, p = 0.07) to experience the urinary flare.: ConclusionsAcute symptoms after I-125 prostate brachytherapy appear to peak 1 month after a prostate implant and return to their baseline values at 1 year. A transient late exacerbation of urinary symptoms is common and can occur in up to half of all patients by 5 years. There appears to be no statistically significant association between a late exacerbation in urinary symptoms and clinical or implant parameters. [Copyright &y& Elsevier]

: PurposeTo calculate the actuarial risk of developing a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, using three definitions of bounce mentioned in the literature, and to explore the relationship between disease and treatment variables and the risk of developing a bounce. The impact of PSA bounce on PSA failure was also explored.: Methods and materialsA total of 373 patients with T1–T2 prostate cancer underwent radioactive seed implant using 125I (n = 337) or 103Pd (n = 36) without hormonal therapy or external beam RT. All patients had a minimum of 1 year (median 4, maximum 11) of follow-up and at least three follow-up PSA values. PSA bounce was defined by a rise of one or two PSA values with a subsequent fall. Three definitions of bounce were used: definition 1, rise ≥0.1 ng/mL; definition 2, rise ≥0.4 ng/mL; and definition 3, rise >35% of previous value.: ResultsThe actuarial likelihood of experiencing a PSA bounce at 5 years was 31% for definition 1, 17% for definition 2, and 20% for definition 3. The median time to develop a bounce was 19.5 months for definitions 1 and 2 and 20.5 months for definition 3. Gleason score, initial PSA level, and clinical stage did not predict for bounce using any definition. Using definition 1, younger patients (≤65 years) had a bounce rate at 5 years of 38% vs. 24% for older patients (p = 0.009). 125I patients receiving an implant dose of ≤160 Gy had a bounce rate (definition 1) at 5 years of 24% vs. 38% for those receiving a dose delivered to 90% of the gland on the 1 month postimplant dose–volume histogram (D90) >160 Gy (p = 0.04). Using definition 2, prostate volume significantly affected the incidence of bounce. Patients with larger glands (>35 cm3) were more likely to experience a bounce (23% at 5 years) than those with smaller glands (≤35 cm3) who had a bounce rate of 11% at 5 years (p = 0.01). In a multivariate analysis of factors predicting for PSA failure, PSA bounce was not found to be significant.: ConclusionPSA bounce is a common phenomenon after prostate brachytherapy and occurs at a rate of 17–31%, depending on the definition used. It is more common in younger patients, those receiving higher implant doses, and those with larger glands. PSA bounce does not predict for future PSA failure. [Copyright &y& Elsevier]

Purpose: To define the optimal dose for 125I prostate implants by correlating post implant CT dosimetry findings with urinary symptoms, biochemical failure, and posttreatment biopsies. Methods and Materials: Patients with T1–T2, Gleason score 2–6 prostate cancer treated with I-125 brachytherapy were analyzed. Group 1 (276 patients) was observed from 18 to 108 months (median, 34 months) and had urinary symptoms prospectively assessed using the International Prostate Symptom Score (IPSS) system. Group 2 (181 patients) observed from 24 to 108 months (median, 44 months) and did not receive hormonal therapy. Implant dose was defined as the D90 (dose delivered to 90% of the prostate on a dose–volume histogram). Patients were analyzed by dose categories: <140 Gy, 140 to <160 Gy, 160 to <180 Gy, and ≥180 Gy. In Group 1, the mean pre- to postimplant IPSS scores were compared in different dose categories by using a matched paired t test. In Group 2, the effect of dose on biochemical control was tested with actuarial methods by using the American Society for Therapeutic Radiology and Oncology definition and on local control with posttreatment biopsies (113 patients). Results: A comparison of pre- with postimplant IPSS revealed no significant changes in scores in the dose groups <180 Gy except for small changes in urgency and bladder emptying in the dose group <140 Gy. In dose group >180 Gy, mean scores changed from 0.5 to 1.0 (p = 0.002) for emptying, 0.76 to 1.29 (p = 0.004) for weak stream, 0.24 to 0.51 (p = 0.009) for straining, 1.55 to 1.82 (p = 0.05) for nocturia, and 6.3 to 8.45 (p = 0.0009) for the total score. Freedom from biochemical failure (FFBF) at 5 years was 68% for doses <140 Gy, 97% for 140 to <160 Gy, 98% for 160 to <180 Gy, and 95% for ≥180 Gy (p = 0.0025). Overall, patients with doses <140 Gy (median follow-up, 66 months) had an FFBF of 68%, compared with 96% for patients with doses ≥140 Gy (median follow-up, 35 months; p = 0.0002). Multivariate analysis found dose to be the most significant factor affecting FFBF. Positive biopsies were found in 23% for doses <140 Gy, 21% for 140 to <160 Gy, 10% for 160 to <180 Gy, and 8% for ≥180 Gy. Overall, biopsies were positive in 22% for doses <160 Gy vs. 9% for ≥160 Gy (p = 0.05). Conclusions: Optimal 125I prostate implants should deliver a D90 of 140–180 Gy, on the basis of postimplant dosimetry. Doses of <140 Gy are associated with increased biochemical failure, and doses >180 Gy with a small increase in long-term urinary symptoms. [Copyright &y& Elsevier]