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Objectives To evaluate the impact of age on overall survival (OS), freedom from distant metastasis (FDM), rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. Materials and methods Three hundred and five consecutive, prospectively evaluated AS patients who underwent a staging transperineal template‐guided mapping biopsy (TTMB) prior to enrollment on AS were evaluated and stratified by age. Evaluated outcomes included OS, FDM, TI, and QOL to include urinary, bowel, sexual function, and depression. Post void residual (PVR) urine measurements were also followed. Repeat biopsy was based on PSA kinetics, abnormal digital rectal examination or patient preference. Results Of the 305 patients, 290 (95.1%) were Gleason 3 + 3 and 15 patients (4.9%) were Gleason 3 + 4. The median follow‐up was 5.5 years (range 1‐14 years). At 10 years, TI was 0%, 1.0%, and 11.4% for patients ≤59, 60‐69, and ≥70 years of age (P

OBJECTIVE The objective of this study was to evaluate the impact of body mass index (BMI) on overall survival, freedom from distant metastases, rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. MATERIALS AND METHODS Three hundred forty consecutive, prospectively evaluated AS patients underwent a staging transperineal template-guided mapping biopsy before AS enrollment and were stratified by BMI ( 35 kg/m2). Evaluated outcomes included overall survival, freedom from distant metastases, TI, QOL to include urinary, bowel, sexual function and depression and serial postvoid residual urine measurements. The relationship between BMI and anterior prostate cancer distribution was evaluated. Repeat biopsy was based on prostate specific antigen kinetics, abnormal digital rectal examination and patient preference. RESULTS Of the 340 patients, 323 (95%) were Gleason 3+3 and 17 patients (5.0%) were Gleason 3+4. The median follow-up was 5.2 years (range: 1 to 14 y). At 10 years, TI was instituted in 4.7%, 2.2%, 9.5%, and 25.0% of patients in BMI cohorts

OBJECTIVES To determine the location and grade of prostate cancer diagnosed by transperineal template-guided mapping (TTMB) after negative transrectal ultrasound-guided (TRUS) biopsy. MATERIALS AND METHODS This analysis consisted of 1118 consecutive patients who underwent TTMB from January 2005 to August 2015. Eight hundred thirty-five underwent TTMB after at least 1 negative TRUS biopsy and 283 underwent TTMB as the first biopsy procedure. The study population was divided into cohorts based on the number of prior TRUS biopsy sessions (0, 1, 2, and ≥3). No patient underwent multiparametric magnetic resonance imaging. Differences in location and cancer grade detected on TTMB were evaluated as a function of the number of prior TRUS biopsies. RESULTS Of the 1118 patients, 679 were diagnosed with prostate cancer. This included 208, 325, 104, and 42 patients who underwent 0, 1, 2, and ≥3 prior TRUS biopsies. The incidence of cancer detection on TTMB decreased as the number of prior TRUS biopsies increased (73.5% vs. 62.4% vs. 51.7% vs. 37.2%, P

Purpose : To evaluate the impact of supplemental external beam radiation therapy (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and erectile function. Material and methods : Patient administered urinary, bowel, and erectile quality of life (QoL) instrument were obtained prior to treatment and following brachytherapy. The study population was comprised of the 457 patients who were alive as of June 2016, had been randomized to two markedly different supplemental EBRT dose regimens and a third arm without supplemental EBRT, and had completed the June 2016 QoL survey. The need for urinary or bowel surgical intervention was prospectively recorded during routine follow-up. Multiple parameters were evaluated for effect on outcomes. Results : The urinary catheter was removed on day 0 in 92.1% of patients and 0.4% required a post-implant transurethral prostatic resection (TURP). On average, the International Prostate Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral strictures was 5.3%. No significant differences were discerned between baseline and post-implant rectal function assessment score (RFAS), and no patient developed a rectal ulcer or fistula. The 10-year potency preservation rate was 50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function. Urethral strictures were most closely related to bulbomembranous urethral brachytherapy doses, post-implant rectal function to pre-implant hemorroidal bleeding, and RFAS and erectile function to pre-brachytherapy international index of erectile function and age. Conclusions : Supplemental EBRT did not significantly effect catheter dependency, IPSS resolution, urethral stricture rate, the need for post-implant TURP, bowel, or erectile function. Careful attention to brachytherapy dose distributions appears to be most important in minimizing post-brachytherapy morbidity.

Purpose: To evaluate prostate-cancer specific mortality (PCSM) in a cohort of high-risk patients treated with a permanent prostate brachytherapy approach, stratified by pre-treatment PSA. Material and methods : 448 high-risk patients (NCCN criteria) underwent permanent prostate brachytherapy. High risk patients were stratified by pre-treatment PSA (≤ 10.0, 10.1-20, and > 20 ng/ml). Biochemical failure (BF), prostate cancer-specific mortality (PCSM), distant failure (DM), and overall mortality (OM) were assessed as a function of prognostic group. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on outcome. Results : The 10-year OM, BF, and PCSM for the entire cohort were 28.5%, 13.3%, and 4.9%, respectively. At 10 years, PCSM was 2.5%, 10.7%, and 4.5% in the PSA ≤ 10, 10.1-20, and > 20 ng/ml groups, respectively. No statistically significant differences in BF or overall survival (OS) were noted when stratified by pre-treatment PSA. DF was the most common in the 10.1-20 ng/ml cohort (8.6% at 10 years). In multivariate analysis, PCSM was most closely related to percent positive biopsies (p = 0.001) and tobacco (p = 0.042). Conclusions : High-risk prostate cancer treated with permanent prostate brachytherapy and supplemental external beam radiotherapy resulted in excellent long-term biochemical control and PCSM. Overall, PCSM was low in all cohorts but highest in the intermediate PSA group (10.1-20 ng/ml).

To evaluate the role of transperineal template-guided mapping biopsy (TTMB) in patients with atypical small acinar proliferation (ASAP) diagnosed via transrectal ultrasound-guided needle biopsy (TRUS). In total, 132 consecutive patients with TRUS-diagnosed ASAP underwent TTMB by means of an anatomic-based technique with sampling of 24 biopsy regions. For each of the 24 regions, 1–3 biopsy cores were obtained (depending on prostate size). No patient underwent pre-biopsy MRI imaging. The Gleason score, location of each positive biopsy core, the number of biopsy cores and percent involvement of each core were recorded. Anterior versus posterior cancer distribution was determined for both low- and high-grade (Gleason score ≥7) cancer. The mean patient age was 63.8 years with a mean PSA of 6.8 ng/mL. Of the 132 patients, 86 (65.2%) were diagnosed with prostate cancer. Of the entire cohort, 47 patients (54.7% of cancer patients and 35.6% of the entire cohort) were diagnosed with Gleason score ≥7. For both low- and high-grade cancers, the anterior gland and especially the anterior apex were the most common cancer locations. In patients with ASAP, TTMB diagnosed prostate cancer in 65.2% of patients and 35.6% of the entire cohort had high-grade prostate cancer. A predilection for anterior-based cancers, especially the anterior apex, was identified. Our study may serve as a baseline reference for MRI-guided biopsy regimens.

To evaluate active surveillance (AS) outcomes including overall survival (OS), freedom from distant metastases (FDM), freedom from therapeutic intervention (FTI), and quality of life (QOL) outcomes in prostate cancer patients using transperineal template-guided mapping biopsy (TTMB) for patient selection. From April 2005–January 2016, 226 consecutive, prospectively evaluated prostate cancer patients underwent TTMB for either low-grade prostate cancer or persistently elevated prostate-specific antigen (PSA) and/or the presence of ASAP. Evaluated outcomes included OS, FDM, FTI and QOL including urinary, bowel, sexual function and depression. Repeat biopsy was based on PSA kinetics and/or abnormal digital rectal examination. Of the 226 patients, 212 (93.8%) were Gleason 3 + 3 and 14 (6.2%) were Gleason 3 + 4. The median follow-up was 5.0 years (range 0.8–13.0 years). The mean prostate volume was 61.3 cm3 with a mean of 59.5 TTMB cores/patient. At the time of AS enrollment, an average of 72.9 cores (TRUS + TTMB) had been obtained for each patient. At 8 years, OS, FTI and FDM were 92.5, 96.8 and 100%. Two hundred and twenty-two patients (98.2%) had a PSA doubling time of more than 3 years. No statistical changes in urinary function, bowel function or depression were noted. At 8 years, 73% of the patients maintained erectile function. Within the confines of the follow-up of this study, the use of TTMB for patient selection identifies a cohort of patients unlikely to develop biochemical or clinical progression and maintain a favorable quality of life.

Purpose: To evaluate biochemical failure (BF) and prostate cancer specific mortality (PCSM) in intermediate-risk (IR) brachytherapy patients stratified into favorable and unfavorable cohorts, and to compare those outcomes to patients with low (LR) and high-risk (HR) disease. Material and methods: From March 1995 till February 2012, 2,502 consecutive patients underwent permanent interstitial brachytherapy for clinically localized prostate cancer. Patients were stratified into risk groups as per the NCCN guidelines with further stratification of the intermediate risk cohort into unfavorable (primary Gleason pattern 4, ≥ 50% positive biopsies or ≥ 2 IR features) and favorable cohorts. Median follow-up was 8.5 years. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure was defined as a PSA > 0.40 ng/ml after nadir. Patients with metastatic prostate cancer or non-metastatic castrate resistant disease who died of any cause were classified as dead of prostate cancer. Multiple parameters were evaluated for effect on outcomes. Results: Fifteen year BF for LR, favorable IR, unfavorable IR, and HR were 1.4%, 2.2%, 7.1%, and 11.1% (p < 0.001), respectively. At 15 years, PCSM for LR, favorable IR, unfavorable IR, and HR was 0.3%, 0.6%, 2.2% and 4.6% (p < 0.001), respectively. In multivariate analysis, BF was best predicted by risk group, pre-implant PSA, percent positive biopsies, prostate volume, and ADT duration, while PCSM was most closely related to risk group, percent positive biopsies and prostate volume. Conclusions: Patients with favorable IR disease have biochemical and PCSM outcomes comparable to those of patients with LR disease. Although unfavorable IR has greater than a 3-fold increased risk of BF and PCSM when compared to favorable IR, the outcomes remain superior to those men with HR disease. J Contemp Brachytherapy 2015; 7, 6: 430-436 DOI: 10.5114/jcb.2015.56763

Purpose Recent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT. Methods and Materials Between April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. Results At 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p = 0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p = 0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p = 0.14). Conclusions Men with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern 5.

We determined the incidence of cancer detection by transperineal template guided mapping biopsy of the prostate in patients with at least 1 previously negative transrectal ultrasound guided biopsy.From January 2005 to January 2012 at least 1 negative transrectal ultrasound guided biopsy was done in 485 patients in our clinical database before proceeding with transperineal template guided mapping biopsy. No study patient had a previous prostate cancer diagnosis. The incidence of patients with 1, 2, or 3 or greater previous transrectal ultrasound guided biopsies was 55.3%, 25.9% and 18.8%, respectively. Transperineal template guided mapping biopsy was done in 74.8% of patients for increasing or occasionally persistently increased prostate specific antigen, in 19.4% for atypical small acinar proliferation and in 5.8% for high grade prostatic intraepithelial neoplasia.For the entire study population a median of 59 cores was submitted at transperineal template guided mapping biopsy. Cancer was ultimately detected in 226 patients (46.6%) using the transperineal template guided method, including 196 (86.7%) with clinically significant disease according to the Epstein criteria. The most common cancer detection site on transperineal template guided mapping biopsy was the anterior apex.Transperineal template guided mapping biopsy detected clinically significant prostate cancer in a substantial proportion of patients with negative transrectal ultrasound guided biopsy. This technique should be strongly considered in the context of increasing prostate specific antigen with failed confirmation of the tissue diagnosis.

Purpose To evaluate the effect of primary Gleason pattern on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) in Gleason 7 prostate cancer patients treated with low-dose-rate (LDR) interstitial brachytherapy with or without supplemental external beam radiation therapy and androgen deprivation therapy. Methods and Materials We retrospectively reviewed the medical records of 932 consecutive patients with biopsy-confirmed Gleason 7 prostate cancer who received LDR interstitial brachytherapy as a component of their definitive treatment regimen. Treatment outcomes were compared between patients with primary Gleason pattern 3 and 4. Results With a median followup of 7.4 years, the 10- and 14-year bPFS, CSS, and OS for the entire Gleason 7 study group were 95.7/95.7%, 98.6/98.6% and 77.2/64.3%, respectively. When biochemical control was evaluated as a function of primary Gleason pattern, the primary pattern 3 had a statistically higher 10- and 14-year bPFS (97.8/97.8% vs. 93.1/93.1%, p = 0.006). The Gleason pattern 3 patients also trended toward a higher 10- and 14-year CSS (99.3/99.3% vs. 96.9/96.9%, p = 0.058). OS was not statistically different between the two Gleason 7 cohorts. Conclusions Gleason 7 prostate cancer patients treated with LDR interstitial brachytherapy have an excellent long-term outcome. There was a small but statistically significant advantage in bPFS and a trend toward improved CSS in patients with a primary Gleason pattern of 3.

Purpose: To explore patterns of time to failure in men receiving high doses of permanent seed brachytherapy with or without external beam radiation therapy as a function of risk status. Material and methods: Two thousand two hundred and thirty four patients were treated with prostate bra chy­ therapy with median follow up of 8.0 years. The population was 35% low risk, 49% intermediate risk, and 16% high risk (NCCN). Median day 0 implant D 90 was 119% and V 100 was 98%. Treatment failure was defined as PSA > 0.40 ng/mL after nadir. Rates of biochemical failure, distant metastases, and prostate cancer death were determined with non­pros­ tate death as a competing risk. Results: For all patients, the 10-year biochemical failure, distant metastases, and cause-specific mortality were 4.4%, 1.4%, and 1.3%, respectively. The biochemical failure rates were 1.3%, 4.8%, and 10.0% for men with low, intermediate, and high risk disease, respectively. Median time to failure was 2.8 years. In men who died from prostate cancer, the median time from treatment failure to death was 4.2 years. Overall, 83% of biochemical failures and 97% of metastases occurred within the first 4 years after treatment. Conclusions: With the dose escalation achieved by high quality brachytherapy dosimetry, even high­risk prostate cancer patients have excellent long term biochemical outcomes. Treatment failures occur early, and one third become metastatic and progress rapidly to prostate cancer death. The low frequency and pattern of failures suggest the pres­ ence of micrometastatic disease prior to treatment is rare, even in high risk patients. J Contemp Brachytherapy 2013; 5, 4: 215–221 DOI: 10.5114/jcb.2013.39210

OBJECTIVES To evaluate whether the use of androgen deprivation therapy (ADT) in prostate brachytherapy patients impacts overall mortality (OM) in patients with lower pretreatment serum testosterone levels compared with those with normal or high baseline serum testosterone. MATERIALS AND METHODS From October 2001 to May 2014, 1916 patients underwent brachytherapy and had a pretreatment serum testosterone. Baseline serum testosterone values were collected prospectively before initiation of therapy. Median follow-up was 7.2 years. In total, 26% of the patients received ADT, primarily men with higher risk disease. OM and prostate cancer-specific mortality were examined to determine whether men with lower baseline serum testosterone were at increased risk of mortality when ADT was used, compared with men with baseline normal or higher testosterone. RESULTS Prostate cancer-specific mortality and OM at 10 years was 0.8% and 22.0%. Age, tobacco use, diabetes, cardiovascular disease, and percent positive biopsies were the strongest predictors of OM. ADT use by itself was not associated with an increased risk of OM on multivariate analysis (P=0.695). However, ADT use in men with lower baseline testosterone was associated with a significantly higher risk of OM (P

Several prominent publications have identified an overall association between tobacco use and an increased risk of disease recurrence and disease-specific mortality in prostate cancer patients. The authors explored whether tobacco use adversely impacts treatment outcomes in men treated with permanent interstitial brachytherapy.From April 1995 to August 2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.5 years. The role of tobacco use as a prognostic factor for biochemical progression-free survival, cause-specific survival, and overall survival was investigated. Differences in survival between smokers and nonsmokers were compared using Kaplan-Meier curves and log-rank tests.Current smokers presented with a lower body mass index (p0.001), smaller prostate size (p=0.003), younger age (p0.001), higher prostate-specific antigen level (p=0.002), a trend toward higher percentage biopsy core involvement (p=0.08), higher incidence of perineural invasion (p=0.015), and higher risk disease (p0.001) than former or nonsmokers. There was no difference in biochemical progression-free survival (p=0.30) or cause-specific survival (p=0.72) at 10 years for smokers compared with nonsmokers. On univariate and multivariate analysis, tobacco use was an adverse risk factor for overall survival (p0.001). There was no association between smoking and any prostate cancer-specific outcome.Smokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers.

Purpose To evaluate outcome in the most unfavorable subset of high-risk prostate cancer patients treated with a combination of supplemental external beam radiation therapy (EBRT) and brachytherapy. Methods and Materials Very high-risk prostate cancer was defined as follows: any Gleason score 10, Gleason score 8–9 with >50% of the biopsy cores positive for malignancy, Gleason score 8–9 with a prostate-specific antigen (PSA) >20 ng/mL, any clinical stage T3, or any PSA >40 ng/mL. One hundred thirty-one patients were identified who met the aforementioned criteria. The median followup was 6.6 years. One hundred twenty (91.6%) patients received supplemental EBRT and 100 (76.4%) received androgen deprivation therapy (median duration, 19.5 months; range, 4–36 months). The median postimplant day 0 D90 (i.e., the minimum percentage of the prescription dose that covers the planning target volume) was 121.9% of prescription dose. Multiple clinical treatment and dosimetric parameters were evaluated for impact on the evaluated survival parameters. Results The median pretreatment PSA and Gleason score were 11.0 ng/mL and 8. One hundred ten (84%) patients had a Gleason score ≥8. At 9 and 12 years, the cause-specific survival, biochemical progression-free survival, and overall survival were 91.0% and 86.5%, 87.3% and 87.3%, and 70.5% and 60.5%, respectively. The most common cause of death was heart disease (22.2%) with deaths from nonprostate cancer (12.7%) and prostate cancer (8.3%) being less likely. Conclusions Permanent interstitial brachytherapy usually with supplemental EBRT and androgen deprivation therapy results in excellent biochemical control and cause-specific survival in the most unfavorable subset of high-risk prostate cancer patients. Death from diseases of the heart was more than twice as likely as death from prostate cancer.

Purpose To determine whether adverse pathologic features, including tumor grade and percent positive biopsy (PPB) cores, predict for prostate size reduction after neoadjuvant cytoreductive therapy. Methods and Materials Eighty-two consecutive patients who were diagnosed with prostate cancer by transperineal template–guided mapping biopsy (TTMB) received neoadjuvant cytoreductive therapy. The median number of biopsy cores was 59. Thirty patients received a leutinizing hormone–releasing hormone agonist and bicalutamide, whereas 52 patients received bicalutamide (50 mg daily) and dutasteride (0.5 mg daily). A transrectal ultrasound volumetric study of the prostate gland and ellipsoid volume determinations of the prostate gland and transition zone (TZ) were obtained immediately before TTMB and at 90 days (±7 days) after the initiation of neoadjuvant medical therapy. Univariate and multivariate regression analyses were performed to identify predictors of prostate gland and TZ volume reduction. Results At TTMB, the mean prostate volumetric and ellipsoid volumes were 55.4 cm3 and 49.0 cm3, respectively. After neoadjuvant medical therapy, the mean volumetric and ellipsoid prostate volumes were 30.8 cm3 and 28.5 cm3, respectively. On average, the prostate volume decreased by 43.9% and 41.0% on volumetric and ellipsoid measurements, respectively. The TZ volume decreased from 19.8 cm3 to 10.1 cm3 (mean volume reduction of 47.7%). In multivariate analysis, prostate volume cytoreduction was most closely associated with PPB (p = 0.014), TTMB prostate volume (p = 0.01), and drug regimen (p = 0.001). Conclusions The degree of prostate volume cytoreduction was positively associated with higher Gleason score and PPBs. Greater reductions in prostate volume may be an indicator of more aggressive cancer.

Purpose The necessity of external beam radiotherapy (EBRT) as a supplement to prostate brachytherapy remains unknown. We report brachytherapy outcomes for patients with higher risk features randomized to substantially different supplemental EBRT regimens. Methods and Materials Between December 1999 and June 2004, 247 patients were randomized to 20 Gy vs. 44 Gy EBRT followed by a palladium-103 boost (115 Gy vs. 90 Gy). The eligibility criteria included clinically organ-confined disease with Gleason score 7–10 and/or pretreatment prostate-specific antigen (PSA) level 10–20 ng/mL. The median follow-up period was 9.0 years. Biochemical progression-free survival (bPFS) was defined as a PSA level of ≤0.40 ng/mL after nadir. The median day 0 prescribed dose covering 90% of the target volume was 125.7%; 80 men received androgen deprivation therapy (median, 4 months). Multiple parameters were evaluated for their effect on bPFS. Results For the entire cohort, the cause-specific survival, bPFS, and overall survival rates were 97.7%, 93.2%, and 80.8% at 8 years and 96.9%, 93.2%, and 75.4% at 10 years, respectively. The bPFS rate was 93.1% and 93.4% for the 20-Gy and 44-Gy arms, respectively ( p = .994). However, no statistically significant differences were found in cause-specific survival or overall survival were identified. When stratified by PSA level of ≤10 ng/mL vs. >10 ng/mL, Gleason score, or androgen deprivation therapy, no statistically significant differences in bPFS were discerned between the two EBRT regimens. On multivariate analysis, bPFS was most closely related to the preimplant PSA and clinical stage. For patients with biochemically controlled disease, the median PSA level was Conclusion The results of the present trial strongly suggest that two markedly different supplemental EBRT regimens result in equivalent cause-specific survival, bPFS, and overall survival. It is probable that the lack of benefit for a higher supplemental EBRT dose is the result of the high-quality brachytherapy dose distributions.

To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment.Between January 2008 and March 2009, 221 consecutive patients underwent Pd-103 brachytherapy without androgen deprivation for clinically localized prostate cancer. Prebrachytherapy prostate-specific antigen (PSA) and serum testosterone were obtained for each patient. Repeat levels were obtained 3 months after brachytherapy and at least every 6 months thereafter. Multiple clinical, treatment, and dosimetric parameters were evaluated to determine an association with temporal testosterone changes. In addition, analysis was conducted to determine if there was an association between testosterone changes and treatment outcomes or the occurrence of a PSA spike.There was no significant difference in serum testosterone over time after implant (p = 0.57). 29% of men experienced an increase ≥ 25%, 23% of men experienced a decrease ≥ 25%, and the remaining 48% of men had no notable change in testosterone over time. There was no difference in testosterone trends between men who received external beam radiotherapy and those who did not (p = 0.12). On multivariate analysis, preimplant testosterone was the only variable that consistently predicted for changes in testosterone over time. Men with higher than average testosterone tended to experience drop in testosterone (p0.001), whereas men with average or below average baseline testosterone had no significant change. There was no association between men who experienced PSA spike and testosterone temporal trends (p = 0.50) nor between initial PSA response and testosterone trends (p = 0.21).Prostate brachytherapy does not appear to impact serum testosterone over time. Changes in serum testosterone do not appear to be associated with PSA spike phenomena nor with initial PSA response to treatment; therefore, PSA response does not seem related to temporal testosterone changes.

Purpose: With widespread prostate-specific antigen (PSA) screening, there has been an increase in men diagnosed with high-risk prostate cancer defined by a Gleason score (GS) $8 coupled with a relatively low PSA level. The optimal management of these patients has not been defined. Cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) were evaluated in brachytherapy patients with aG S$8 and a PSA level #15 ng/mL with or without androgen-deprivation therapy (ADT). Methods and Materials: From April 1995 to October 2005, 174 patients with GS $8 and a PSA level #15 ng/mL underwent permanent interstitial brachytherapy. Of the patients, 159 (91%) received supplemental external beam radiation, and 113 (64.9%) received ADT. The median follow-up was 6.6 years. The median postimplant Day 0 minimum percentage of the dose covering 90% of the target volume was 121.1% of prescription dose. Biochemical control was defined as a PSA level #0.40 ng/mL after nadir. Multiple parameters were evaluated for impact on survival. Results: Ten-year outcomes for patients without and with ADT were 95.2% and 92.5%, respectively, for CSS (p = 0.562); 86.5% and 92.6%, respectively, for bPFS (p = 0.204); and 75.2% and 66.0%, respectively, for OS (p = 0.179). The median post-treatment PSA level for biochemically controlled patients was

Study Type – Prognosis (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Cardiovascular disease is a leading cause of death in prostate cancer patients. Pretreatment ED is a surrogate for vascular pathology. Aggressive treatment of medical co-morbidity in prostate cancer patients may positively impact overall survival. OBJECTIVE • To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy. PATIENTS AND METHODS • In all, 1279 consecutive patients with clinically localized prostate cancer and pre-implant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) underwent brachytherapy. • Potency was defined as an IIEF-6 score of ≥13 without pharmacological or mechanical support. • Patients were stratified into IIEF-6-score cohorts (≤12, 13–23 and 24–30). • The median follow-up was 5.0 years. RESULTS • The 8-year overall survival (OS) of the study population was 85.1%. • The 8-year OS for IIEF-6scores ≤12, 13–23 and 24–30 were 78.0%, 92.8% and 91.4%, respectively (P

Standard prostate biopsy schemes underestimate Gleason score in a significant percentage of cases. Extended biopsy improves diagnostic accuracy and provides more reliable prognostic information. In this study, we tested the hypothesis that greater biopsy core number should result in improved treatment outcome through better tailoring of therapy.From April 1995 to May 2006, 1,613 prostate cancer patients were treated with permanent brachytherapy. Patients were divided into five groups stratified by the number of prostate biopsy cores (≤6, 7-9, 10-12, 13-20, and20 cores). Biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were evaluated as a function of core number.The median patient age was 66 years, and the median preimplant prostate-specific antigen was 6.5 ng/mL. The overall 10-year bPFS, CSS, and OS were 95.6%, 98.3%, and 78.6%, respectively. When bPFS was analyzed as a function of core number, the 10-year bPFS for patients with20, 13-20, 10-12, 7-9 and ≤6 cores was 100%, 100%, 98.3%, 95.8%, and 93.0% (p0.001), respectively. When evaluated by treatment era (1995-2000 vs. 2001-2006), the number of biopsy cores remained a statistically significant predictor of bPFS. On multivariate analysis, the number of biopsy cores was predictive of bPFS but did not predict for CSS or OS.Greater biopsy core number was associated with a statistically significant improvement in bPFS. Comprehensive regional sampling of the prostate may enhance diagnostic accuracy compared to a standard biopsy scheme, resulting in better tailoring of therapy.

Objective To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in high-risk prostate cancer brachytherapy patients. Patients and methods From April 1995 to June 2005, 284 patients with high-risk prostate cancer (Gleason score ≥ 8 or prostate-specific antigen > 20 ng/mL or clinical stage ≥ T2 c) underwent brachytherapy. Supplemental external beam radiation therapy was given to 257 (90.5%) patients and 179 (63.0%) received androgen deprivation therapy (ADT). Median follow up was 7.8 years. The median post-implant day 0 D90 was 118.9% of prescription dose. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead from prostate cancer. Multiple parameters were evaluated for impact on survival. Results Twelve-year CSS, bPFS and OS were 94.2%, 89.0% and 69.7%. On multivariate analysis, bPFS was best predicted by percent positive biopsies and ADT. The analysis failed to identify any predictors for CSS, while OS was highly correlated with patient age, percent positive biopsies and diabetes. Fourteen percent of patients died from diseases of the heart, while 8%, 8% and 6% of patients died from non-prostate cancer, other causes and prostate cancer, respectively. When OS was stratified by patients with 0-3 vs ≥ 4 comorbidities, the 12-year OS was 73.0% and 52.7% (P = 0.036). Conclusions High-quality brachytherapy results in favourable bPFS and CSS for high-risk patients. Death from diseases of the heart is more than twice as likely as death from prostate cancer. Strategies to improve cardiovascular health may positively impact OS.

To investigate the dosimetry, treatment-related morbidity, and biochemical outcomes for brachytherapy in patients with prostate glands20 cm(3).From November 1996 to October 2006, 104 patients with prostate glands20 cm(3) underwent brachytherapy. Multiple prostate, urethral, and rectal dosimetric parameters were evaluated. Treatment-related urinary and rectal morbidity were assessed from patient questionnaires. Cause-specific survival, biochemical progression-free survival, and overall survival were recorded.The median patient age, follow up, and pre-treatment ultrasound volume was 64 years, 5.0 years and 17.6cm(3), respectively. Median day 0 dosimetry was significant for the following: V100 98.5%, D90 126.1% and R1000.5% of prescription dose. The mean urethral and maximum urethral doses were 119.6% and 133.8% of prescription. The median time to International Prostate Symptom Score resolution was 4 months. There were no RTOG grade III or IV rectal complications. The cause-specific survival, biochemical progression-free survival, and overall survival rates were 100%, 92.5%, and 77.8% at 9 years. For biochemically disease-free patients, the median most recent postbrachytherapy PSA value was 0.02 ng/mL.Our results demonstrate that brachytherapy for small prostate glands is highly effective, with an acceptable morbidity profile, excellent postimplant dosimetry, acceptable treatment-related morbidity, and favorable biochemical outcomes.

Transrectal ultrasound (TRUS) biopsy can miss 20-30% of clinically significant cancers. We evaluate an alternative approach-transperineal template-guided mapping biopsy (TTMB) in the initial and repeat biopsy setting. From January 2005 through September 2008, 373 consecutive men underwent TTMB (294 men withor =1 prior negative biopsy and 79 men as the initial biopsy). The location of each positive biopsy core, number of positive cores, and percent involvement of each core was recorded. Cancer detection rate for the initial biopsy was 75.9%. For men with 1, 2, andor =3 prior negative biopsies detection rates were 55.5%, 41.7%, and 34.4%, respectively. In all, 55.5% of the cancers identified were Gleasonor =7. The majority of the cancers were multifocal. There was no significant change in the number of positive cores or Gleason score as the number of prior biopsies increased. The anterior and apical aspects of the prostate were among the most common cancer locations. TTMB provides a high rate of cancer detection as initial and repeat biopsy. TTMB was particularly effective at diagnosing anterior and apical cancer. TTMB may have particular application for men considering active surveillance, with prior negative TRUS biopsies, and those considering subtotal gland or other minimally invasive treatments.

Results: The median maximum, mean, and minimum doses delivered to the colon or rectum affected by the sCRC were 39.3 (range, 0.2-66.0), 5.4 (range, 0.2-41.3) and 0.6 (range, 0.2-7.8) Gy, respectively. The estimated rectal doses after prostate RT were significantly higher (p\0.001) than those delivered to non-rectal colic structures, but only 1 (9%) patient presented a rectal cancer. The differential mean dose administered to the rectosigmoid junction and sigmoid colon, with or without sCRC, were not significantly different (p = 0.2 and p = 0.3, respectively). Results: Six year bPFS, cause-specific survival (CSS) and overall survival (OS) were 98.3%, 99.8%, and 90.7%, respectively. Comparing patients with low or low normal testosterone to those with average or higher testosterone, there was no significant dif- ference in bPFS (97.9% vs. 98.4%, p = 0.71), CSS (99.7% vs. 100%, p = 0.95) or OS (90.6% vs. 90.6%, p = 0.95). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no signif- icant difference in bPFS or CSS comparing patient who did or did not receive ADT. However, overall survival was significantly decreased in patients with baseline lower testosterone levels who also received ADT (83.5% vs. 94.3%, p = 0.002). Overall, 43 patients have died with only 1 patient dead of metastatic prostate cancer. In patients with average and higher pretreatment testos- teronelevels,15patientshavediedwith3(20%)attributedtocardiovasculardisease.Incontrast,inpatientswithloworlownormal testosterone, 14 of the 28 (50%) deaths have been related to cardiovascular disease. Conclusions: Low pretreatment testosterone levels alone did not impact disease recurrence or overall survival. However, patients with baseline low testosterone who also received ADT experienced a decrease in overall survival.

BACKGROUND: In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. METHODS AND MATERIAL: From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progres- sion-free survival (bPFS) was defined as a prostate-specific antigen (PSA)

Purpose: Toevaluatethe primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. Methods and Materials: From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression‐free, and overall survival. Results: The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and highrisk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. Conclusions: Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily resulted from an excess of cardiovascular deaths. Changes in lifestyle to improve cardiovascular health may improve overall survival in patients with clinically localized prostate cancer. 2008 Elsevier Inc. Prostate cancer, Primary causes of death, Brachytherapy, ADT.

Purpose Acute prostate brachytherapy-related morbidity is dominated by urinary symptomatology. In this study, we evaluated the effect of severe early brachytherapy-related urinary morbidity on late urinary function. Methods and materials From January 1998 to September 2003, 1029 patients were implanted for clinical stage T1b–T3a (2002 American Joint Committee on Cancer [AJCC] criteria) prostate cancer. Five hundred sixteen (50.1%) received supplemental external beam radiation therapy and 440 (42.8%) received androgen deprivation therapy. Severe acute urinary morbidity (SAUM) was defined as a dysuria frequency score of at least 4 (of 5), a dysuria severity score of at least 8 (of 10), an internation prostate symptom score (IPSS) elevated to at least 30 or 15 above preimplant value for 4 weeks, and/or requirement of a urinary catheter for at least 5 days. Dysuria severity and frequency resolution were defined as a return to within one point of baseline. IPSS resolution was defined as a return to within two points of baseline. Results Of the 1029 patients, 175 met at least one of the criteria for inclusion. Dysuria frequency resolved in 5.0 vs. 1.3 weeks and dysuria severity in 5.7 vs. 1.4 weeks, for patients with and without SAUM. The mean time for IPSS resolution was 13.8 vs. 6.6 weeks, for patients with and without SAUM. The incidence of transurethral resection (2.3% [4/173] vs. 1.5% [13/841]) and bulbomembranous urethral strictures (2.2% [4/175] vs. 1.8% [15/854]) were comparable among patients with and without SAUM. Conclusions Patients experiencing brachytherapy-related SAUM have long-term urinary function and complications comparable to patients who did not develop SAUM.

PURPOSE Recent studies have suggested that extracapsular brachytherapy treatment margins correlate with biochemical control. It is likely that volumetric geographic dosimetric parameters will be more robust than selected radial measurements. Accordingly, we evaluated extracapsular volumetric dosimetric parameters in low-risk patients. MATERIALS AND METHODS A total of 263 low-risk prostate cancer patients randomized to Pd-103 versus I-125 were implanted with a brachytherapy target volume consisting of the prostate with a 5-mm periprostatic margin. The median follow-up was 4.2 years. All patients were implanted at least 3 years prior to analysis. Within 2 hours of implantation, an axial CT was obtained for postimplant dosimetry. A 5-mm three-dimensional periprostatic anulus was constructed around the prostate and evaluated in its entirety and in 90 degrees segments. Prostate and anular dosimetric parameters consisted of V100/V150/V200 and D90. Biochemical progression-free survival (bPFS) was defined as a PSA < or =0.50 ng/mL after nadir. RESULTS The Pd-103 and I-125 arms were well-matched in terms of clinical, biochemical, and pathologic presentation. Six-year bPFS was 96.8% versus 99.2% for I-125 versus Pd-103 (P = 0.149). The most recent median posttreatment PSA was

Purpose: To evaluate the effect of prostate brachytherapy with or without supplemental therapies on long-term rectal function by means of a patient-administered quality-of-life instrument. Materials and Methods: As part of an ongoing prospective evaluation, 164 of an initial 209 patients who remain alive were mailed the Rectal Function Assessment Score (R-FAS) with a prestamped return envelope. R-FAS range from 0 to 27 with lower scores being indicative of better bowel function. Of the 162 eligible patients, 161 (99.4%) returned the survey. Median follow-up was 9.0 years (range 8.2–11.2 years). Clinical, treatment, and dosimetric parameters evaluated for bowel function included patient age, diabetes, hypertension, tobacco consumption, clinical T stage, elapsed time since brachytherapy, ultrasound volume, planning target volume, androgen deprivation therapy, supplemental external beam radiation, isotope, rectal dose, prostate D100/D150/D200, and prostate D90. Results: For the entire cohort, the current R-FAS was 3.59, which represented a nonstatistical improvement from prior surveys in 1999 (4.29) and 2002 (3.92) (P 0.134). Only 16 patients (9.9%) reported bowel function to be worse after brachytherapy. Of the clinical, treatment, and dosimetric parameters evaluated, only the number of preimplant bowel movements, tobacco use, and diabetes correlated with R-FAS. Despite lower rectal doses with 103 Pd, isotope did not predict for bowel function. Consistent with prior surveys, patient perception of overall rectal quality of life was inversely related to supplemental external beam radiation (P 0.027). Conclusion: Prostate brachytherapy adversely affects bowel function. However, in most patients the changes are minimal and slowly resolve with time. Overall rectal quality of life is inversely related to supplemental external beam radiation.

Purpose: Long-term biochemical relapse-free survival (BRFS) rates in patients with clinical Stages T1-T3 prostate cancer continue to be scrutinized after treatment with external beam radiation therapy and brachytherapy. Methods and Materials: We report 15-year BRFS rates on 223 patients with clinically localized prostate cancer that were consecutively treated with I 125 or Pd 103 brachytherapy after 45-Gy neoadjuvant EBRT. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified American Society for Therapeutic Radiology and Oncology consensus definition (two consecutive serum prostate-specific antigen rises) as the outcome. Gleason scoring was performed by the pathologists at a community hospital. Time to biochemical failure was calculated and compared by using Kaplan-Meier plots. Results: Fifteen-year BRFS for the entire treatment group was 74%. BRFS using the Memorial Sloan-Kettering risk cohort analysis (95% confidence interval): low risk, 88%, intermediate risk 80%, and high risk 53%. Grouping by the risk classification described by D'Amico, the BRFS was: low risk 85.8%, intermediate risk 80.3%, and high risk 67.8% ( p = 0.002). Conclusions: I 125 or Pd 103 brachytherapy combined with supplemental EBRT results in excellent 15-year biochemical control. Different risk group classification schemes lead to different BRFS results in the high-risk group cohorts.

BACKGROUND The impact of primary Gleason pattern was determined on cause-specific (CSS), biochemical progression-free (bPFS), and overall survival (OS) after brachytherapy for Gleason score 7 prostate cancer. METHODS From April 1995 to October 2003, 530 patients underwent brachytherapy for Gleason score 3+4 (n = 300) or Gleason 4+3 (n = 230) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. The median follow-up was 5.7 years. Of the 530 patients, 412 (77.7%) received supplemental external beam radiation therapy (XRT) and 177 (33.4%) received androgen deprivation therapy. bPFS was defined by a prostate-specific antigen (PSA) ≤0.40 ng/mL after nadir. Multiple parameters were evaluated as predictors of CSS, bPFS, and OS. RESULTS At 10 years, Gleason 3+4 versus 4+3 did not predict for CSS (96.7% vs 93.3%, P = .506), bPFS (97.0% vs 92.9%, P = .085), or OS (77.0% vs 78.0%, P = .933). Cox linear regression analysis demonstrated that clinical stage and radiation dose (D90) predicted for CSS, whereas pretreatment PSA, clinical stage, and prostate size predicted for bPFS. Patient age, diabetes, and tobacco were the strongest predictors for OS. To date, 57 patients have died, with 80.7% due to cardiovascular/pulmonary events or secondary malignancies. Five patients have died of prostate cancer. CONCLUSIONS The primary Gleason pattern did not impact CSS, bPFS, or OS in Gleason score 7 prostate cancer. Deaths from cardiovascular/pulmonary disease and second malignancies were 9.6 times more common than death from prostate cancer. Cancer 2007. © 2007 American Cancer Society.

To evaluate whether supplemental external beam radiotherapy (EBRT) is essential to maximize Pd-103 brachytherapy outcomes in patients with unfavorable intermediate-risk (IR) disease.A total of 630 patients were assessed from two prospective randomized brachytherapy trials evaluating the role of supplemental EBRT in patients with higher risk features. Patients were stratified into unfavorable IR (primary Gleason pattern 4, ≥50% positive biopsies, or ≥2 IR features), favorable IR, and high-risk (HR) cohorts. Median follow-up was 7.5 years. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a prostate-specific antigen0.40 ng/mL after nadir. Patients with metastatic prostate cancer or nonmetastatic castrate-resistant disease who died of any cause were classified as dead of prostate cancer. Multiple parameters were evaluated for effect on outcomes.The 10-year BF for favorable IR, unfavorable IR, and HR was 1.7%, 6.6%, and 15.5% (p0.001). At 10 years, prostate cancer-specific mortality (PCSM) and overall mortality (OM) were 0% and 20.4%, 2.1% and 23.2%, and 4.3% and 42.4% for favorable IR, unfavorable IR, and HR. Although unfavorable IR patients had a greater incidence of BF, PCSM, and OM when compared with favorable IR, neither the addition nor dose of supplemental EBRT influenced outcome.Outcomes for favorable IR were superior to those with unfavorable IR. Within the confines of this study, neither the addition nor dose of supplemental EBRT influenced BF, PCSM, or OM in patients with IR disease.

Purpose To determine whether a previously reported substratification system can be extrapolated to patients with high-risk prostate cancer treated with permanent interstitial brachytherapy. Methods and Materials Four hundred six National Comprehensive Cancer Network patients with high-risk prostate cancer treated with permanent prostate brachytherapy with or without supplemental external beam radiotherapy were stratified into good (prostate-specific antigen >20 or Gleason score ≥8 or ≥T3), intermediate (prostate-specific antigen >20 and ≥T3), and poor (Gleason score ≥8 with ≥1 additional high-risk feature) prognostic cohorts. Because of only 1 patient with intermediate high-risk disease, the analysis was performed on patients in the good and poor cohorts. Biochemical failure (BF), prostate cancer–specific mortality (PCSM), distant metastasis, and overall mortality were assessed as function of prognostic group. Multiple parameters were evaluated for impact on outcome. Results With a median followup time of 7.9 years, 10- and 14-year rates of BF and PCSM for the entire cohort were 7.8% and 3.7%, respectively. The BF rate was significantly greater in the poor prognostic category (16.8% vs. 7.8%, p = 0.041). The poor prognostic category was the strongest predictor of BF in univariate and multivariate analyses. No statistically significant differences in PCSM, distant metastasis, or overall mortality were identified between the good and poor prognostic categories. Conclusions Patients with high-risk prostate cancer treated with a brachytherapy approach have excellent long-term biochemical control and cancer-specific survival. The poor prognostic high-risk category had a higher rate of BF compared with the good prognostic category without a higher rate of PCSM or distant metastasis.

Purpose To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 (103Pd) brachytherapy for high-risk prostate cancer patients. Methods and Materials Trial 44/20 randomized patients to 44 Gy plus 90 Gy 103Pd vs. 20 Gy with 115 Gy 103Pd, and the subsequent trial randomized patients to the 20 Gy arm vs. 125 Gy 103Pd without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7–9 and/or a pretreatment prostate-specific antigen (PSA) 10–20 ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40 ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes. Results In 44/20 trial, 13-year BF, prostate cancer–specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20 Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0 Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of Conclusions With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8–9 was too small to determine the role of supplemental EBRT in that cohort.

Previous studies have evaluated whether metformin is associated with prostate cancer incidence and outcomes with conflicting conclusions. In this study, we evaluate the incidence of prostate cancer in diabetic patients treated with and without metformin compared with nondiabetic patients. One thousand thirty-four patients underwent transperineal template-guided mapping biopsy secondary to either an elevated prostate-specific antigen (PSA) or a prior biopsy finding of atypical small acinar proliferation/prostatic intraepithelial neoplasia. The cohort included 881 nondiabetic men, 65 diabetic men treated with metformin, and 88 diabetic men not receiving metformin. In metformin-treated patients, the median duration of usage was 6.0 years. Differences in prostate cancer diagnosis, histologic grade, and tumor volume were compared across the 3 cohorts. There was no statistically significant differences discerned between the 3 cohorts in patient age, prebiopsy PSA, prostate volume, PSA density, PSA doubling time, PSA velocity, or the total number of prior transrectal ultrasound biopsy sessions. Five hundred eighty-four patients were diagnosed with prostate cancer. There was no difference in prostate cancer diagnosis (P=0.153), Gleason score (P=0.960), the number of positive biopsy cores (P=0.764), or risk group stratification (P=0.877) between the 3 cohorts. In multivariate analysis, only older age predicted for prostate cancer diagnosis. In terms of Gleason score ≥7, patient age, PSA velocity, and body mass index predicted for more aggressive histology. Neither diabetes, metformin use or duration was of statistical consequence. Metformin did not impact incidence of prostate cancer diagnosis, Gleason score distribution, or volume of disease.

OBJECTIVE To report the biochemical progression-free survival (BPFS) in hormone-naive men aged ≤ 54 years who underwent brachytherapy with or without supplemental external beam radiation therapy (EBRT), as despite favourable biochemical control rates with brachytherapy, there remains a reluctance to recommend non-extirpative approaches for young men with clinically localized prostate cancer. PATIENTS AND METHODS From April 1995 to October 2002, 108 hormone-naive patients aged ≤ 54 years (median 52 years, range 45–54) had permanent interstitial brachytherapy for clinical stage T1c-T2c NXM0 (2002 American Joint Committee on Cancer staging) prostate cancer. No patient had a seminal vesicle biopsy or pathological lymph node staging. The mean (sd, median) follow-up was 5.3 (1.8, 4.8) years. BPFS was defined by a prostate-specific antigen (PSA) level of ≤ 0.40 ng/mL after the nadir. Risk groups were assigned using the Memorial Sloan-Kettering Cancer Center criteria. Several clinical, treatment and dosimetric variables were evaluated for their effect on BPFS. RESULTS For the entire group, the actuarial 8-year BPFS was 96%; for low- (57 men), intermediate- (47) and high- (four) risk patients, the BPFS rates were 96%, 100% and three of four, respectively. For biochemically disease-free patients, the median PSA level after treatment was 0.05 ng/mL. In a multivariate analysis, only pretreatment PSA level predicted biochemical control, while dosimetry variables after treatment were almost statistically significant. CONCLUSIONS Hormone-naive patients aged ≤ 54 years have a high probability of a good 8-year BPFS after permanent interstitial brachytherapy with or without supplemental EBRT.

Objectives To evaluate the cytoreductive effectiveness of combined neoadjuvant bicalutamide and dutasteride before prostate brachytherapy for clinically localized prostate cancer. Methods From April 2003 to May 2005, 31 patients opted for cytoreduction with bicalutamide (50 mg daily) and dutasteride (0.5 mg daily). Before, and at 3 months (90 ± 5 days) after, the initiation of medical therapy, all patients underwent a transrectal ultrasound volumetric study of the prostate gland, with ellipsoid volume determination of the prostate gland and transition zone. The variables analyzed included pretreatment and posttreatment prostate and transition zone volumes and changes in width, height, and length of the prostate gland and transition zone. A multivariate analysis was performed to identify predictors for prostate gland and transition zone volume reduction. Results Before the initiation of bicalutamide and dutasteride, the mean prostate volume was 54.3 cm 3 by planimetric summation and 49.7 cm 3 by ellipsoid volume calculation. After a 3-month course of combination medical therapy, the average prostate volume was 36.1 cm 3 (33.6% reduction) and 32.5 cm 3 (34.6% reduction) using the volumetric and ellipsoid volume determinations, respectively. Bicalutamide and dutasteride resulted in a 39.8% reduction in transition zone volume (20.8 cm 3 versus 12.4 cm 3 ). The prostate gland and transition zone dimensions (width, height, and length) decreased about 11.4% to 19.9%. Conclusions The prostate gland and transition zone volume reductions after a 3-month course of neoadjuvant bicalutamide and dutasteride are comparable to previous reports of volume reduction using a luteinizing hormone-releasing hormone agonist with or without an antiandrogen.

To evaluate the influence of isotope and prostate size on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after prostate brachytherapy.Between January 1998 and June 2003, 976 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (2002 American Joint Committee on Cancer) prostate cancer. Seven hundred eighty-nine (80.8%) were implanted with 103Pd and 187 (19.2%) with 125I. The median follow-up was 41.2 months. Patients were stratified into size cohortsor = 25 cm3, 25.1-35 cm3, 35.1-45 cm3, and45 cm3. Four hundred eighteen patients (42.8%) received androgen deprivation therapy (ADT). Four hundred eighty-six patients (49.7%) received supplemental external-beam radiation therapy (XRT). In all patients, an alpha blocker was initiated before implantation and continued at least until the IPSS returned to baseline. IPSS resolution was defined as a return to within one point of baseline. The median number of IPSS determinations per patient was 21. Clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment PSA, Gleason score, clinical T stage, percent positive biopsies, preimplant IPSS, ultrasound volume, planning volume, isotope, V(100/150/200), D(90), urethral dose (average and maximum), supplemental XRT, ADT, and the duration of ADT (or = 6 months vs.6 months). Catheter dependency and the need for postsurgical intervention were also evaluated.For both isotopes and all prostate size cohorts, IPSS peaked 1 month after implantation and returned to baseline at a mean of 1.9 months. Stratification of prostate size cohorts by isotope demonstrated no significant differences in prolonged catheter dependency (or = 5 days), IPSS resolution, or postimplant surgical intervention. In Cox regression analysis, IPSS normalization was best predicted by preimplant IPSS, XRT, and any need for a catheter after brachytherapy. Catheter dependency correlated with prostate size and ADT, whereas the need for surgical intervention was most closely related to any catheter dependency, maximum urethral dose, ADT, and maximum IPSS increase.Regardless of prostate size, isotope did not impact IPSS resolution, catheter dependency, or the need for postbrachytherapy surgical intervention. Although prostate size did predict for short-term (5 days) catheter dependency, it did not influence IPSS resolution or the need for surgical intervention.

Objectives. To conduct a preliminary investigation on statin use and its impact on clinical presentation and biochemical progression-free survival after brachytherapy. Methods. A total of 512 consecutive patients were treated with permanent brachytherapy for clinical Stage T1c-T3aNxM0 prostate cancer at least 3 years before analysis. Biochemical progression-free survival was defined by a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after nadir. The median follow-up was 5.3 years. The clinical, treatment, and dosimetric parameters evaluated included use of any and specific statins, age, body mass index, PSA level, Gleason score, percentage of positive biopsies, perineural invasion, prostate volume, planning volume, dosimetric quality, supplemental external beam radiotherapy, tobacco use, hypertension, and diabetes. Results. The actuarial 8-year biochemical progression-free survival rate for the entire group was 94.6%. On forward conditional Cox regression analysis, the pretreatment PSA level and percentage of positive biopsies were statistically significant predictors of biochemical outcome. However, a significantly lower pretreatment PSA level, percentage of positive biopsy cores, and PSA density and earlier clinical stage were found in the statin group. Almost every clinical presentation parameter comparison at least favored statin users. When stratified by any or specific statin use, 97.0% of patients taking statins compared with 94.3% not taking statins and 97.8% of patients taking atorvastatin compared with 94.7% taking other statins were free of biochemical progression. Conclusions. The results of this brachytherapy investigation with the longest reported follow-up period to date suggest that statins, especially atorvastatin, may improve most clinical presentations with a nonsignificant improvement in 8-year biochemical progression-free survival. UROLOGY 66: 1150‐1154, 2005. © 2005 Elsevier Inc.

Objectives. To evaluate the relationship between pretreatment postvoid residual urine (PVR) less than 100 mL and brachytherapy-related urinary morbidity. Methods. A total of 204 patients with a pretreatment PVR measurement underwent permanent prostate brachytherapy with urethral-sparing techniques (100% to 140% minimal peripheral dose) for clinical Stage T1b–T2c (2002 American Joint Committee on Cancer staging system) prostate cancer. The median follow-up was 11.7 months. Evaluation of urinary morbidity consisted of the time to International Prostate Symptom Score (IPSS) resolution, length of catheter dependency, and the need for postimplant surgical intervention. IPSS resolution was defined as a return to within 1 point of the score at baseline. In all patients, an alpha-blocker was initiated before implantation and continued at least until the IPSS returned to baseline. Statistically significant predictors of urinary morbidity were determined using Cox regression analysis of multiple clinical, treatment, and dosimetric parameters. Results. For the entire cohort, the mean time to IPSS resolution was 2.5 months. The urinary catheter was removed on the day of implantation in 171 patients (83.8%), with no patient remaining catheter dependent for more than 3 days. To date, no patient has required postimplant surgical intervention. On multivariate analysis, pretreatment PVR predicted for clinically irrelevant differences in IPSS resolution and did not influence catheter dependency. Conclusions. The selection of patients with a pretreatment PVR of less than 100 mL was associated with rapid IPSS resolution, the absence of prolonged (more than 3 days) catheter dependency, and the elimination of postbrachytherapy surgical intervention for bladder outlet obstruction. UROLOGY 66: 1266–1270, 2005. © 2005 Elsevier Inc.

OBJECTIVE To evaluate the incidence and temporal resolution of dysuria after permanent prostate brachytherapy, and to identify predictors of brachytherapy-related dysuria. PATIENTS AND METHODS The study included 130 patients with no history of transurethral resection of the prostate before treatment, who had brachytherapy on one of two prospective randomized trials, with explicitly planned and executed urethral-sparing techniques (100–150% minimum peripheral dose) using either 103Pd or 125I for clinical T1c–T2c prostate cancer. The median follow-up was 22.6 months. An α-blocker was initiated either prophylactically 2 weeks before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to normal, or withheld until the onset of significant brachytherapy-related urinary morbidity. Dysuria was evaluated on a 0–10 scale, before brachytherapy and then at 1, 3, 6 and 12 months afterward, with a median of four dysuria questionnaires per patient. Clinical, treatment and dosimetric variables evaluated included α-blocker, age, IPSS before and the maximum after treatment, prostate volume on ultrasonography, hormonal status, supplemental radiotherapy, isotope, urethral dose, V100/200, D90, and time to obtaining a normal IPSS. RESULTS The maximum incidence of dysuria was 85% at 1 month after brachytherapy, with subsequent resolution over time. The use of prophylactic tamsulosin resulted in a statistically lower dysuria severity score (difference of 2.7 vs 4.2, P

Purpose To determine the effect of urethral dose on dysuria after permanent prostate brachytherapy. Methods and materials One hundred eight patients without a preimplant history of a transurethral resection underwent brachytherapy on one of two prospective randomized trials for clinical T1c–T2c (2002 AJCC) prostate cancer. Urethral dose was stratified into cohorts of

PURPOSE The purpose of this article is to evaluate the impact of prostate size and the magnitude of cytoreduction after neoadjuvant androgen-deprivation therapy (ADT) on catheter dependency, urinary symptomatology, and need for postbrachytherapy surgical intervention. MATERIALS AND METHODS From February 1998 to August 2002, 186 consecutive patients underwent monotherapeutic brachytherapy (no supplemental external-beam radiotherapy or ADT), and 101 consecutive patients received < 6 months of ADT (a luteinizing hormone-releasing hormone agonist and an anti-androgen) in conjunction with brachytherapy without supplemental external-beam radiotherapy for clinical Tlc-T2b (2002 American Joint Committee on Cancer) prostate cancer. ADT was initiated approximately 3 months before brachytherapy. The median follow-up was 38.6 months. An α-blocker was initiated before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to baseline levels. Evaluated parameters included patient age, pretreatment prostate-specific antigen, Gleason score, clinical T stage, preimplantation IPSS, ultrasound volume, hormonal status, isotope, D 9 0 , V 1 0 0 / 1 5 0 / 2 0 0 , and urethral dose (average and maximum). RESULTS Patients receiving neoadjuvant ADT were statistically older, presented with higher preimplantation IPSS scores, and larger prostate volumes. Patients receiving ADT were likelier to require a urinary catheter for the first 3 days after implantation; however, by day 4, no statistical difference in catheter dependency could be discerned between the two cohorts. Hormonal status did not predict for postbrachytherapy surgical intervention. IPSS returned to baseline at a mean of 1.8 and 1.7 months in hormone-naive and ADT patients, respectively. In multivariate Cox regression analysis, the preimplantation IPSS and the maximum postimplantation IPSS predicted for IPSS normalization overall and in both cohorts. Ultrasound prostate volume did not predict for IPSS normalization, catheter dependency, or need for postimplantation surgical intervention. CONCLUSION Although patients receiving ADT were likelier to require a urinary catheter for the first three days after implantation, hormonal manipulation did not affect IPSS normalization, prolonged catheter dependency, or need for postbrachytherapy surgical intervention in these patients treated with brachytherapywithout supplemental external-beam radiotherapy.

Purpose To determine the effect of transurethral resection on urinary function after permanent prostate brachytherapy using a validated, patient-administered, quality-of-life (QOL) instrument. Methods and materials Twenty-seven consecutive brachytherapy patients with clinical T1b-T2b (1997 American Joint Commission on Cancer) prostate cancer and a history of either preimplant or postimplant transurethral resection of the prostate (TURP) were evaluated. Of the 27 patients, 1 continued to be catheter dependent and was excluded from analysis. Of the remaining 26 patients, each was mailed the urinary function component of the Expanded Prostate Cancer Index (EPIC) and the International Prostate Symptom Score (IPSS). Twenty-six surveys (100%) were returned. The mean and median follow-up was 44.8 and 39.8 months, respectively. The clinical, treatment, and dosimetric parameters evaluated included age, pretreatment prostate-specific antigen level, Gleason score, stage, risk group, prostate volume, presence of diabetes and hypertension, tobacco consumption, number of TURPs, number of grams resected, ultrasound planning volume, hormonal status, supplemental external beam radiotherapy, isotope, follow-up (in months), minimal dose received by 90% of the prostate gland, percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose, and the average and maximal urethral dose. Because baseline IPSSs, but not EPIC scores, were available, a cross-sectional survey was performed in which 51 newly diagnosed prostate cancer patients yet to receive any therapeutic intervention and 195 non-TURP brachytherapy patients served as controls. Results For all evaluated parameters, superior urinary scores were noted in the preimplant TURP group, with intermediate scores in the postimplant TURP patients and poor urinary QOL scores in the pre- and postimplant TURP patients. With time, the EPIC scores improved in the pre- and postimplant TURP cohorts. In multivariate linear regression analysis of the EPIC urinary summary score, the number of TURPs and supplemental external beam radiotherapy were the strongest predictors for diminished QOL. Conclusion TURP results in diminished urinary QOL after brachytherapy. However, patients who underwent preimplant TURP had urinary QOL approaching that of non-TURP brachytherapy patients. Significant urinary dysfunction was noted in approximately one-half of patients who underwent postimplant TURP (especially pre- and postimplant TURP). Because most patients with brachytherapy-related urinary obstruction will eventually spontaneously void, TURP should be approached with extreme caution and only after substantial time has transpired.

PURPOSE: To evaluate the effect of hormonal manipulation on catheter dependency, the resolution of urinary symptomatology, and the need for postbrachytherapy transurethral/transincisional resection (TURP/TUIP). METHODS AND MATERIALS: Seven hundred sixteen consecutive patients (median follow-up, 29 months) underwent brachytherapy for clinical T1b-T3a (1997 AJCC) prostate cancer from January 1998 through August 2002. Of the evaluated cohort, 400 patients were hormone nao ¨ve, 227 received short-course cytoreductive (6 months) hormonal therapy, and 89 received extended (6 months) hormonal therapy. An α-blocker was initiated prior to implantation and continued at least until the International Prostate Symptom Score (I-PSS) returned to baseline levels. Evaluated parameters included age, T-stage, preimplant I-PSS, ultrasound volume, treatment planning volume, hormonal status, supplemental external beam radiation therapy (XRT), isotope, urethral dose, total implant activity, D90, and V100/150/200. Catheter dependency and the incidence of TURP/TUIP were also evaluated. RESULTS: Six hundred fifty three patients (91.2%) had the urinary catheter permanently removed on day 0 with 15 patients (2.1%) requiring a catheter beyond 4 days. The I-PSS returned to within 1 point of the antecedent value at a median of 4 months. Sixteen patients (2.2%) underwent postimplant TURP/TUIP. A Cox regression indicated that preimplant I-PSS, supplemental XRT, planning target volume, hormonal therapy, and number of seeds were the strongest predictors for I-PSS resolution. Using all available data, the strongest predictors for I-PSS at 18 months following brachytherapy included variants of I-PSS, isotope, and days of catheter dependency. The maximum I-PSS, planning target volume, and XRT best predicted for prolonged (4 days) catheter dependency. The need for postimplant TURP/TUIP was most closely associated with days of catheter dependency and the maximum increase in I-PSS. However, when only data available prior to implantation was entered into the model, hormonal therapy predicted for postsurgical intervention. CONCLUSIONS: In this retrospective evaluation, hormonal manipulation did not statistically impact short-term or prolonged urinary catheter dependency or I-PSS at 18 months, but did influence time to I-PSS normalization and the need for postbrachytherapy surgical intervention. 2004 American Brachytherapy Society. All rights reserved.

PURPOSE The purpose of this paper was to evaluate the relationship between the percentage of positive biopsies and the biochemical outcome in hormone-naive patients undergoing permanent prostate brachytherapy with or without supplemental external-beam radiation therapy. MATERIALS AND METHODS Four hundred thirteen hormone-naive patients underwent prostate brachytherapy for clinical T1c-T2b NxMO (1997 American Joint Committee on Cancer classification) adenocarcinoma of the prostate gland from April 1995 through June 2001. The median patient age was 66.9 years, and the median pretreatment prostate-specific antigen value was 6.8 ng/mL. The median follow-up was 52 months. Patients were stratified by percentage of positive biopsy results into the following cohorts: 50%. The influences of percentage of positive biopsy results, patient age, clinical T stage, Gleason score, pretreatment prostate-specific antigen value, risk group, prostate volume, supplemental external-beam radiation therapy, isotope, percentage of prescribed dose covering 90% of the target volume (D 9 0 ), and volume receiving 100%, 150%, and 200% of the prescribed dose (V 1 0 0 / 1 5 0 / 2 0 0 ) were evaluated. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiology and Oncology consensus definition. RESULTS For all 413 patients, the 7-year actuarial freedom from biochemical progression rate was 99.4%, 94.3%, and 89.2% when stratified by percentage of positive biopsy results in the 50% groups, respectively. When low-, intermediate-, and high-risk patients were stratified by percentage of positive biopsy results, a nonsignificant trend for increased biochemical progression was noted with increasing positive biopsy results. In multivariate analysis, percentage of positive biopsy results and pretreatment prostate-specific antigen value were the only significant predictors of biochemical outcome. The median postimplantation prostate-specific antigen value for all biochemically disease-free patients was < 0.1 ng/mL, regardless of risk group or percentage of positive biopsy results cohort. DISCUSSION Multivariate analysis demonstrated that percentage of positive biopsy results and pretreatment prostate-specific antigen value were statistically significant predictors of 7-year biochemical progression-free survival. However, the relatively small absolute differences in biochemical outcome based on percentage of positive biopsy results may be a result of radiation dose escalation with the utilization of generous periprostatic treatment margins.