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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]

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]

Purpose We analyzed factors influencing 15-year cause specific and all-cause survival in men treated with prostate brachytherapy. Materials and Methods A total of 1,669 men with a median age of 66 years who had T1-T3 prostate cancer were treated with prostate brachytherapy and followed a mean of 10 years. Treatments were implant alone, implant plus hormone therapy, or external beam irradiation or implant plus hormone therapy plus external beam irradiation. Hormone therapy was administered in 898 men (53.8%) for a median of 6 months. Cause specific and all-cause survival were estimated by the Kaplan-Meier method with comparisons made by logistic regression and Cox proportions hazard rates. Results The 15-year cause specific survival rate was 94.1%. Cause specific survival in the 3 NCCN® risk groups was 96.3%, 97.5% and 85.2% (p <0.001). Hormone therapy did not positively impact cause specific survival. The 15-year all-cause survival rate was 57%. Cox regression revealed age (HR 1.09, p <0.001), hormone therapy (HR 1.04, p = 0.032), diabetes (HR 1.86, p = 0.013), atrial fibrillation (HR 2.90, p = 0.041), smoking (HR 1.42, p = 0.030) and emphysema (HR 8.20, p = 0.040) as significant associations. At 15 years hormone therapy decreased all-cause survival from 60.3% to 54.9% (p = 0.009). All-cause survival was not reduced when hormone therapy was limited to 6 months or less (p = 0.005). This difference was present in men 66 years old or younger (p = 0.017) and in older men (p = 0.05). Conclusions Prostate brachytherapy yields favorable 15-year cause specific survival, especially in patients at high risk. All-cause survival is less in patients with preexisting diabetes, atrial fibrillation and emphysema. Hormone therapy for longer than 6 months has a negative effect on all-cause survival even in younger patients without an apparent beneficial effect on cause specific survival. [ABSTRACT FROM AUTHOR]

Purpose: To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis. Methods and Materials: A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities. Results: Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model. Conclusions: Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT. [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]

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: 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]

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]

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]

The author reflects on the study by M. Gaztañaga and J. Crook regarding prostate-specific antigen (PSA) bounce following prostate seed implant. The authors of the study found that PSA measurements can be misguiding in the first three years due to frequency of temporary benign rises. He mentions that most PSA bounce literature does not recognize between low- and high-risk patients.

Objective: To characterize cystoscopy findings performed for cause after prostate brachytherapy in men. Materials and Methods: A retrospective review of cystoscopy reports in 2532 men treated with prostate brachytherapy with or without external beam radiation therapy for clinically localized prostate cancer between 1990 and 2011 was performed. We investigated the relationship between relevant clinical and demographic characteristics with the development of particular cystoscopic findings in patients with hematuria or lower urinary tract symptoms. Results: One hundred eighty-five of 2532 men (7.3%) underwent cystoscopy for gross or microscopic hematuria or refractory urinary symptoms at a median time of 2.7 years after implantation and were followed up for a median of 5.9 years after treatment. Most had a negative cystoscopy finding, whereas in 67 of 185 (36.2%), the findings included bladder tumors in 18 (27%), hypervascularity in 18 (27%), radiation cystitis in 13 (19.4%), inflammation in 7 (10.4%), urethral stricture in 5 (7.5%), and calculus disease in 6 (8.9%). Cystoscopic findings did not significantly differ when stratified by cystoscopy indication (P = .515). Bladder tumors were identified in similar proportions among men with gross hematuria (9.6%) and refractory urinary symptoms (10.3%, P = .840). Conclusion: Cystoscopy after brachytherapy performed for cause demonstrates a relatively low incidence of benign and malignant pathologies. Detection of bladder tumors was uncommon, although equally observed among men with hematuria and urinary symptoms. Low threshold to perform cystoscopy should be considered in men with hematuria or persistent lower urinary tract symptoms after prostate brachytherapy. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: We investigated whether earlier PSA failure following prostate brachytherapy is associated with increased rates of distant metastases (DM), prostate cancer-specific mortality (PCSM), and overall mortality. Materials and methods: We retrospectively analyzed 2818 patients who underwent brachytherapy±external beam radiation therapy (EBRT)±androgen deprivation therapy (ADT). With median follow-up of 5.52years, 264 patients experienced PSA failure at a median time of 3.25years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5years, 3years, or 5years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS). Results: Among patients with PSA failures, 69 (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other causes. Patients with rapid PSA failures demonstrated increased rates of DM, PCSM, and overall mortality, despite higher total BED and longer ADT. In multivariate analysis with a PSA failure interval <3years, the hazard ratio (HR) for DM was 3.92 (95% CI: 2.34–6.55; p =0.000); HR for PCSM was 2.79 (95% CI: 1.45–5.38; p =0.002); and HR for overall mortality was 2.28 (95% CI: 1.50–3.48; p =0.000). Conclusion: Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality. [Copyright &y& Elsevier]

Background and purpose: Rectal bleeding can occur following radiotherapy for prostate cancer and negatively impacts quality of life for cancer survivors. Treatment and clinical factors do not fully predict rectal bleeding, and genetic factors may be important. Materials and methods: A genome-wide association study (GWAS) was performed to identify SNPs associated with the development of late rectal bleeding following radiotherapy for prostate cancer. Logistic regression was used to test the association between 614,453 SNPs and rectal bleeding in a discovery cohort (79 cases, 289 controls), and top-ranking SNPs were tested in a replication cohort (108 cases, 673 controls) from four independent sites. Results: rs7120482 and rs17630638, which tag a single locus on chromosome 11q14.3, reached genome-wide significance for association with rectal bleeding (combined p-values 5.4×10−8 and 6.9×10−7 respectively). Several other SNPs had p-values trending toward genome-wide significance, and a polygenic risk score including these SNPs shows a strong rank-correlation with rectal bleeding (Sommers’ d =5.0×10−12 in the replication cohort). Conclusions: This GWAS identified novel genetic markers of rectal bleeding following prostate radiotherapy. These findings could lead to the development of a predictive assay to identify patients at risk for this adverse treatment outcome so that dose or treatment modality could be modified. [ABSTRACT FROM AUTHOR]

Objective: To report the outcomes and late toxicities in younger patients with long-term follow-up treated with brachytherapy with or without external beam radiotherapy for prostate adenocarcinoma. Materials and Methods: Patients treated with brachytherapy with or without external beam radiotherapy who were aged ≤60 years at treatment with ≥10 years of follow-up were selected from our database. The outcomes were analyzed regarding biochemical failure, distant metastases, and cause of death. Genitourinary outcomes were assessed using the International Prostate Symptom Score, Radiation Therapy Oncology Group, and Common Terminology Criteria for Adverse Events criteria. Gastrointestinal toxicity was measured using Radiation Therapy Oncology Group scales. Erectile dysfunction was measured using Sexual Health Inventory for Men and the Mount Sinai Erectile Function score. Results: A total of 131 patients met the inclusion criteria, with a median age of 57 years at treatment and a median follow-up of 11.5 years. Of the patients in this cohort, 9.9% developed biochemical failure with 1 failure and 1 prostate cancer-related death after 10 years. The International Prostate Symptom Score were statistically unchanged after 10 years. Of 22 cases (17%) of grade 2 or greater genitourinary toxicities, only 6 (4.5%) continued after 10 years. Of 11 cases (8.3%) of grade 2 or greater gastrointestinal events, none persisted past 10 years. A significant decrease occurred in the mean Sexual Health Inventory for Men score from 19.5 to 15.3 (P = .008). Of the potent patients before treatment, 69% remained potent at last follow-up. A total of 4 second malignancies were detected, 2 of which were within the radiation field. Conclusion: Men <60 years old who underwent brachytherapy for prostate cancer can expect minimal late genitourinary and gastrointestinal toxicity after 10 years and excellent potency preservation. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the relationship between the onset of erectile dysfunction and dose to the penile bulb and neurovascular bundles (NVBs) after real-time ultrasound-guided prostate brachytherapy. Methods and Materials: One hundred forty-seven patients who underwent prostate brachytherapy met the following eligibility criteria: (1) treatment with 125I brachytherapy to a prescribed dose of 160 Gy with or without hormones without supplemental external beam radiation therapy, (2) identification as potent before the time of implantation based on a score of 2 or higher on the physician-assigned Mount Sinai Erectile Function Score and a score of 16 or higher on the abbreviated International Index of Erectile Function patient assessment, and (3) minimum follow-up of 12 months. Median follow-up was 25.7 months (range, 12–47 months). Results: The 3-year actuarial rate of impotence was 23% (34 of 147 patients). An additional 43% of potent patients (49 of 113 patients) were using a potency aid at last follow-up. The penile bulb volume receiving 100% of the prescription dose (V100) ranged from 0–0.05 cc (median, 0 cc), with a dose to the hottest 5% (D5) range of 12.5–97.9 Gy (median, 40.8 Gy). There was no correlation between penile bulb D5 or V100 and postimplantation impotency on actuarial analysis. For the combined right and left NVB structures, V100 range was 0.3–5.1 cc (median, 1.8 cc), and V150 range was 0–1.5 cc (median, 0.31 cc). There was no association between NVB V100 or V150 and postimplantation impotency on actuarial analysis. Conclusion: Penile bulb doses are low after real-time ultrasound-guided prostate brachytherapy. We found no correlation between dose to either the penile bulb or NVBs and the development of postimplantation impotency. [Copyright &y& Elsevier]

Objective: To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific castration-resistant prostate cancer (CRPC) treatments.Materials and Methods: The Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for metastatic CRPC based on available data and clinical experience.Results: A consensus was developed to address important questions on management of patients with metastatic CRPC.Conclusion: In the absence of large-scale clinical trials, the Working Group recommends that patients may best be managed with a layered approach of approved therapies with unique or complimentary mechanisms of action. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor of "Mayo Clinic Proceedings" about an investigation on morbidity after brachytherapy for prostate adenocarcinoma.

Abstract: Objectives: To present our treatment algorithm and 20-year experience in treating prostate cancer with brachytherapy since 1990, with focus on cancer-control outcomes and treatment-related morbidity. Methods and materials: We selected patients treated for localized prostate cancer with brachytherapy, combination therapy with external beam radiotherapy, and adjuvant androgen deprivation therapy as prescribed by our Mount Sinai risk stratification and treatment algorithm. Outcomes were analyzed with respect to biochemical failure, distant metastases, prostate cancer-specific survival, and overall survival. Morbidity was assessed with respect to urinary, sexual, and rectal outcomes. Results: In total, 2,495 patients met inclusion criteria. The 12-year actuarial freedom from biochemical failure was 83% (low risk: 90%, intermediate risk: 84%, and high risk: 64%); freedom from distant metastasis was 95%; prostate cancer-specific survival was 95%; and overall survival was 70%. On multivariate analysis, significant associations were found between cancer control and risk group, total biologically effective dose, and androgen deprivation therapy. With regard to morbidity, potency was preserved in 61%, and urinary symptoms improved in 35%. The 12-year actuarial freedom from urinary retention events was 90% and from severe rectal bleed was 93%. Conclusions: Brachytherapy, as administered via the Mount Sinai algorithm, remains an efficacious and benign treatment option for patients with localized prostate cancer of all risk groups. [Copyright &y& Elsevier]

Abstract: Purpose: To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB). Methods and Materials: The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS. Results: Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography–based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography–magnetic resonance image fusion is viewed as useful, but not mandatory. Conclusions: Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians. [Copyright &y& Elsevier]

Abstract: Purpose: To evaluate the efficacy of multimodality therapy consisting of hormone therapy (HT), brachytherapy (BT), and external beam radiotherapy (EBRT) in extraprostatic prostate cancer and identify factors with predictive value. Methods and Materials: Between June 1992 and October 2006, 97 patients with extraprostatic prostate cancer received permanent seed implant BT. Extraprostatic disease was defined by one or more of the following: positive seminal vesicle biopsy (n =56), positive lymph node dissection (n =8), or a clinical tumor stage of T3 (n =48). Treatment consisted of BT alone with 103Pd or 125I (n =4); HT and BT (n =3); BT and EBRT (n =2); or trimodality therapy with HT, BT, and EBRT (n =88). Median followup was 69 (range, 23–182) months. Freedom from biochemical failure (FBF) rates were calculated using the Phoenix criteria. Results: The 7-year actuarial FBF, freedom from distant metastases, disease-specific survival, and overall survival rates were 67%, 82%, 96%, and 81%, respectively. Biologically effective dose (BED) was the only variable significantly impacting FBF rates. FBF at 7 years was 60% vs. 74% for BED below 200 and 200 or above, respectively (p =0.048). Trends toward worse outcomes were noted with increasing Gleason score, with 7-year FBF rates of 86% vs. 71% vs. 55% for scores of 6 or less, 7, and 8–10, respectively (p =0.090). BED was the only significant predictor of FBF in multivariate analysis (p =0.032). None of the predictors were significant in multivariable analyses for the other outcomes studied. Conclusions: Trimodality approach achieves durable biochemical control in most patients with historically poor prognosis T3 prostate cancer. BED above 200Gy was associated with superior FBF. [Copyright &y& Elsevier]

Purpose: To evaluate retrospectively the biochemical outcomes of young men treated with low-dose-rate brachytherapy for prostate cancer. Methods and Materials: From 1990 to 2005, 1,665 men with clinically localized prostate cancer were treated with low-dose-rate brachytherapy ± hormone therapy (HT) ± external beam radiotherapy and underwent ≥2 years of follow-up. Patients were stratified on the basis of age: ≤60 (n = 378) and >60 years (n = 1,287). Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine the association of variables with freedom from biochemical failure (FFbF). Results: Median follow-up was 68 months (range, 24–180) for men ≤60 years and 66 months (range, 24–200) for men >60. For the entire group, the actuarial 5- and 8-year FFbF rates were 94% and 88%, respectively. Men ≤60 demonstrated similar 5- and 8-year FFbF (95% and 92%) compared with men >60 (93% and 87%; p = 0.071). A larger percent of young patients presented with low-risk disease; lower clinical stage, Gleason score (GS), and pretreatment PSA values; were treated after 1997; did not receive any HT; and had a high biologic effective dose (BED) of radiation (all ps <0.001). On multivariate analysis, PSA (p = 0.001), GS (p = 0.005), and BED (p < 0.001) were significantly associated with FFbF, but age was not (p = 0.665). Conclusion: Young men achieve excellent 5- and 8-year biochemical control rates that are comparable to those of older men after prostate brachytherapy. Young age should not be a deterrent when considering brachytherapy as a primary treatment option for clinically localized prostate cancer. [Copyright &y& Elsevier]