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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]

Purpose: We identified single nucleotide polymorphisms associated with change in the AUA Symptom Score after radiotherapy for prostate cancer. Materials and Methods: A total of 723 patients treated with brachytherapy with or without external beam radiation therapy were assessed at baseline and annually after radiotherapy using the AUA Symptom Score. A 2-stage genome-wide association study was performed with the primary end point of change in AUA Symptom Score from baseline at each of 4 followup periods. Single nucleotide polymorphism associations were assessed using multivariable linear regression adjusting for pre-radiotherapy AUA Symptom Score severity category and clinical variables. Fisher's trend method was used to calculate combined p values from the discovery and replication cohorts. Results: A region on chromosome 9p21.2 containing 8 single nucleotide polymorphisms showed the strongest association with change in AUA Symptom Score (combined p values 8.8×10−6 to 6.5×10−7 at 2 to 3 years after radiotherapy). These single nucleotide polymorphisms form a haplotype block that encompasses the inflammation signaling gene IFNK. These single nucleotide polymorphisms were independently associated with change in AUA Symptom Score after adjusting for clinical predictors including smoking history, hypertension, α-blocker use and pre-radiotherapy AUA Symptom Score. An additional 24 single nucleotide polymorphisms showed moderate significance for association with change in AUA Symptom Score. Several of these single nucleotide polymorphisms were more strongly associated with change in specific AUA Symptom Score items, including rs13035033 in the MYO3B gene, which was associated with straining (beta coefficient 0.9, 95% CI 0.6–1.2, p = 5.0×10−9). Conclusions: If validated, these single nucleotide polymorphisms could provide insight into the biology underlying urinary symptoms following radiotherapy and could lead to development of an assay to identify patients at risk for experiencing these effects. [Copyright &y& Elsevier]

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]

What's known on the subject? and What does the study add? While the frequencies and severity of late toxicities following prostate brachytherapy are well known, less has been published with regard to time to first onset. Several series with limited median follow-up have published time to onset. An extensive analysis of timing to late toxicity following brachytherapy for cervical cancer has also been published. This study is the largest of its kind with the longest median follow-up to capture very late events. It can provide a basis for physician and patient education about when late toxicities can reasonably be expected to occur. The study also shows that a significant amount of erectile dysfunction might be more age related than radiation induced. OBJECTIVES To assess the timing of first onset of late rectal bleeding, late haematuria and erectile dysfunction (ED) following brachytherapy with or without external beam radiation therapy (EBRT) for prostate adenocarcinoma., To identify treatment factors and patient characteristics that affect the time to first onset., PATIENTS AND METHODS In all, 2046 patients were definitively treated for prostate adenocarcinoma with a full 125I or 103Pd implant or a partial 103Pd implant followed by EBRT with 6 years median follow-up (range 2-17 years)., Patients were selected for an event of Radiation Therapy Oncology Group (RTOG) grade 2 or greater rectal bleeding, ≥RTOG grade 2 haematuria, or a drop in the Mount Sinai Erectile Dysfunction Score from potent to impotent (excluding patients who received androgen deprivation therapy)., Life tables were generated to calculate actuarial incidence rates of toxicity., Wilcoxon rank sum and Cox regression were utilized to identify treatment factors affecting time to onset., RESULTS The incidence rate per 1000 patients for 0-2 years, 2-5 years and 5-10 years following radiation for rectal bleeding is 14.3, 15.9 and 6.5, respectively; for haematuria, 14.0, 8.2 and 1.3, respectively; and for ED, 82.4, 48.2 and 42.2, respectively., Just 5% of rectal bleeding occurs after 5 years from radiation vs 18% of haematuria cases and 22% of ED., On multivariate analysis, time to first onset of rectal bleeding was affected by the addition of EBRT only whereas the time to onset of haematuria was affected by the biological effective dose of the radiation and the addition of EBRT., The only factor on multivariate analysis to affect time to onset of ED was the age of the patient at treatment, independent of radiation dose or technique., CONCLUSIONS Unique temporality to first onset of selected toxicities was observed in patients after radioactive implant for prostate adenocarcinoma with or without EBRT., Clinicians and patients should be counselled when to expect late toxicities., The only factor to affect time to onset of ED is the age of the patient, suggesting possible over-reporting of radiation-induced ED in the light of normal age-related events. [ABSTRACT FROM AUTHOR]

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]

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: We investigated the factors that influenced urinary symptoms in the first 10 years after prostate brachytherapy. Materials and Methods: A total of 1,932 men were treated with prostate brachytherapy alone or with external beam irradiation and followed a mean of 6.8 years. The influence of pretreatment American Urological Association symptom score (7 or less, 8 to 19, 20 or greater), external beam radiotherapy, 125I or 103Pd, biological effective dose, age, prostate size and hormone therapy on the change in American Urological Association symptom score (11,491) was compared. Results: The mean change from initial score (7.4) was 11.4, 5.5, 3.3, 2.7, 1.5, 1.2, 1, 1, 1, 1, 1.3 and 1.4 points at 3, 6 months and 1 to 10 years, respectively (p <0.001). Factors that resulted in a greater increase in urinary symptoms at year 1 were low pretreatment score (p <0.001), no hormonal therapy (p <0.001), younger age (p = 0.046) and higher biological effective dose (p = 0.025). At 10 years patients with an initial score of 20 or greater had an average decrease of 11 points compared to a decrease of 0.9 for an initial score of 8 to 19 and an increase of 2.7 for an initial score of 7 or less (p <0.001). On linear regression the scores at 1 year were influenced by initial score (p <0.001), biological effective dose (p = 0.022), prostate size (p <0.001) and hormonal therapy (p = 0.009). At 10 years only the pretreatment score remained significant (p <0.001). Conclusions: There is minimal change in mean American Urological Association symptom score (1.4 points) 10 years after prostate brachytherapy. Patients presenting with high initial scores have the greatest improvement from baseline. Biological effective dose, external beam radiotherapy, hormonal therapy, isotope, patient age and prostate size do not appear to influence long-term urinary symptoms. [Copyright &y& Elsevier]

Purpose: We describe how treatment factors influence biochemical freedom from failure, local control, freedom from metastasis and cause specific survival in patients treated with prostate brachytherapy. Materials and Methods: We followed 2,111 men who underwent brachytherapy a median of 6 years (range 2 to 17). Median prostate specific antigen was 7 ng/ml. Of the men 1,455 (68.9%) had clinical stage T2a or less and 1,428 (67.6%) had Gleason score less than 7. A total of 1,171 patients (55.5%) received 125I, 221 (10.4%) received 103Pd and 719 (34.1%) received supplemental external beam irradiation combined with 103Pd. Post-implant dosimetry was done 30 days after implantation with doses converted to the biologically effective dose. Prostate biopsy was done 2 years after permanent prostate brachytherapy in 586 men (27.8%). Survival functions were determined by the Kaplan-Meier method and Cox regression with proportions tested by the log rank test. Results: The 12-year biochemical freedom from failure rate was 78.6%, and stage, Gleason score, prostate specific antigen and biologically effective dose were significant predictors (p = 0.007, <0.001, 0.005 and <0.001, respectively). In 964 patients at low risk the biochemical freedom from failure rate was 88.1% and significant predictors were hormonal therapy (p = 0.030), prostate specific antigen (p = 0.026) and biologically effective dose (p = 0.003). In 499 patients at intermediate risk the biochemical freedom from failure rate was 79.2% with biologically effective dose a significant predictor (p <0.001). In 648 men at high risk the biochemical freedom from failure rate was 67% and significant predictors were hormonal therapy, Gleason score and biologically effective dose (p = 0.036, <0.001 and 0.012, respectively). The local failure rate was 7.3% with biologically effective dose a significant predictor (p <0.001). Prostate biopsy was positive in 21 of 121 cases (21.5%) for a biologically effective dose of 150 Gy2 or less, in 14 of 248 (5.6%) for greater than 150 to 200 Gy2 and in 3 of 193 (1.6%) for greater than 200 Gy2 (p <0.001). The 12-year freedom from metastasis rate was 95.2% with Gleason score a significant predictor (p <0.001). Cause specific survival at 12 years was 94.5% with Gleason score and biologically effective dose significant predictors (p <0.001 and 0.027, respectively). Conclusions: Permanent prostate brachytherapy yields excellent long-term oncologic outcomes. High biologically effective dose may need to be delivered to achieve successful biochemical freedom from failure, local control and cause specific survival. [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: We evaluated the effect of neoadjuvant hormonal therapy on urinary function in men with a prostate volume of 50 cc or greater undergoing prostate brachytherapy. Materials and Methods: A total of 395 men with 50 cc or greater glands were treated with 3 months of neoadjuvant hormonal therapy (204) or implantation alone (191). Urinary function was assessed by the International Prostate Symptom Score, the urinary retention incidence and subsequent transurethral prostate resection. Results: Median patient age was 67 years and median followup was 6 years. Mean prostate volume in neoadjuvant hormonal therapy cases was 72.9 cc, which decreased to 54.3 cc after 3 months (p <0.001). Mean prostate volume in cases without hormonal therapy was 60.6 cc (p <0.001). Urinary retention occurred in 16 of 191 men (8.4%) without vs 25 of 204 (12.3%) with hormonal therapy (p = 0.207). The median duration of urinary retention was 42 days (range 2 to 243). There were no significant associations of urinary retention with prostate size, prostate or urethral dose, or pre-implantation International Prostate Symptom Score. Of patients without hormonal therapy retention occurred in 3 of 12 (25%) with a pre-implantation International Prostate Symptom Score of 15 or greater and in 13 of 168 (7.7%) with a score of less than 15 (OR 4.0, 95% CI 1–16, p = 0.04). In contrast, there was no difference in the retention rate in patients with hormonal therapy with an initial score of 15 or greater vs less than 15 (2 of 25 or 8% vs 11 of 102 or 10.8%, p = 0.614). Transurethral prostate resection was done in 11 of 191 men (5.8%) without vs 12 of 204 (5.9%) with hormonal therapy (p = 0.958). There was no difference in biochemical failure in the 2 groups. Conclusions: Neoadjuvant hormonal therapy has its greatest benefit in patients receiving brachytherapy who have a large prostate and an International Prostate Symptom Score of 15 or greater. [Copyright &y& Elsevier]

Purpose: We assessed the impact of androgen suppressive therapy on biochemical failure in patients with intermediate risk prostate cancer treated with brachytherapy and external beam irradiation. Materials and Methods: From 1994 to 2006, 432 patients with intermediate risk prostate cancer as defined by the National Comprehensive Cancer Network were treated with low dose rate brachytherapy and external beam irradiation with or without 9 months of androgen suppressive therapy. Gleason score was 7 in 76% of cases and prostate specific antigen was 1.4 to 20 ng/ml (median 7.6). Of the patients 350 received androgen suppressive therapy and 82 did not. The biologically effective dose was 142 to 280 Gy2 (median 206). Followup was 23 to 155 months (median 56). Results: The overall 8-year biochemical failure-free rate using the Phoenix definition in patients with vs without androgen suppressive therapy was 92% vs 92% (p = 0.4). The therapy had no significant impact on the biochemical failure-free rate in patients with Gleason score 7 (92% vs 90.5%, p = 0.55), prostate specific antigen 10 to 20 ng/ml (92% vs 100%, p = 0.32), T2b-T2c disease (89.5% vs 97%, p = 0.27) and more than 1 intermediate risk feature (90% vs 100%, p = 0.2). Conclusions: We addressed the relative importance of radiation dose vs hormonal therapy for intermediate risk prostate cancer. With high biologically effective dose combination treatment androgen suppressive therapy did not have a significant impact on the 8-year biochemical failure-free rate. We question its routine use in this setting. [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: 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]

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]