Impact of Androgen Deprivation Therapy on Overall Mortality in Prostate Brachytherapy Patients With Low Pretreatment Testosterone Levels.

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<0.01). ADT use in men with normal or higher baseline testosterone was not associated with an increased OM risk (P=0.924). CONCLUSIONS: Men with lower baseline testosterone may be at increased risk of premature death when ADT is utilized compared with men with baseline normal or higher testosterone. Further analysis of this potential risk factor is warranted to further identify subsets of men who may be at higher risk of long-term adverse sequelae from ADT.

Prostate cancer-specific death in brachytherapy treated high-risk patients stratified by pre-treatment PSA.

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).

Metformin Does Not Predict for Prostate Cancer Diagnosis, Grade, or Volume of Disease After Transperineal Template-guided Mapping Biopsy.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Metformin did not impact incidence of prostate cancer diagnosis, Gleason score distribution, or volume of disease.

Incidence, grade and distribution of prostate cancer following transperineal template-guided mapping biopsy in patients with atypical small acinar proliferation.

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Is supplemental external beam radiation therapy essential to maximize brachytherapy outcomes in patients with unfavorable intermediate-risk disease?

PURPOSE: To evaluate whether supplemental external beam radiotherapy (EBRT) is essential to maximize Pd-103 brachytherapy outcomes in patients with unfavorable intermediate-risk (IR) disease. METHODS AND MATERIALS: 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 antigen >0.40 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. RESULTS: The 10-year BF for favorable IR, unfavorable IR, and HR was 1.7%, 6.6%, and 15.5% (p < 0.001). 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. CONCLUSIONS: 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.

Is supplemental external beam radiation therapy necessary for patients with higher risk prostate cancer treated with 103Pd? Results of two prospective randomized trials.

PURPOSE: To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 ((103)Pd) brachytherapy for high-risk prostate cancer patients. METHODS AND MATERIALS: Trial 44/20 randomized patients to 44 Gy plus 90 Gy (103)Pd vs. 20 Gy with 115 Gy (103)Pd, and the subsequent trial randomized patients to the 20 Gy arm vs. 125 Gy (103)Pd 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 <0.02 ng/mL. 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.

Stratification of brachytherapy-treated intermediate-risk prostate cancer patients into favorable and unfavorable cohorts.

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.

Metformin is not associated with improved biochemical free survival or cause-specific survival in men with prostate cancer treated with permanent interstitial brachytherapy.

PURPOSE: Several recent studies have suggested improved clinical outcomes in diabetic men with prostate cancer who also use metformin. We explore whether metformin use is associated with improved outcomes specifically in men undergoing prostate brachytherapy. MATERIAL AND METHODS: 2,298 consecutive patients underwent permanent interstitial brachytherapy by a single brachytherapist (GSM). The cohort included 2028 non-diabetic men, 144 men with diabetes who were not taking metformin, and 126 men with diabetes who were taking metformin. Median follow up was 8.3 years. Differences in biochemical free survival, cause specific survival, and overall survival between men taking metformin and those not taking metformin were compared using Kaplan-Meier curves and log rank tests. RESULTS: Fifteen year biochemical failure rate, cause specific mortality and overall mortality for non-diabetic men was 4.6%, 1.5%, 47.0%, respectively; for diabetic men taking metformin 4.8%, 2.0%, 37.2%; and for diabetic men not taking metformin was 2.8%, 0%, 72.7%, respectively. Metformin use was not predictive in multivariate analysis of biochemical failure or prostate cancer specific mortality. However, diabetic men not taking metformin had higher overall mortality than non-diabetic men. CONCLUSIONS: Metformin use was not associated with improved biochemical survival or cancer specific survival in this cohort of men treated with prostate brachytherapy.

Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy.

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.

Incidence and pathological features of prostate cancer detected on transperineal template guided mapping biopsy after negative transrectal ultrasound guided biopsy.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Transperineal template-guided mapping biopsy as a staging procedure to select patients best suited for active surveillance.

OBJECTIVES: Patients with clinically insignificant prostate cancer are candidates for active surveillance. However, uncertainty regarding the true extent of disease limits enthusiasm. In this study, we report our initial findings in patients with transrectal ultrasound (TRUS)-detected clinically insignificant prostate cancer undergoing transperineal template-guided mapping biopsy (TTMB) as a staging procedure. METHODS: Sixty-four patients who met the Epstein criteria for clinically insignificant prostate cancer underwent TTMB. Each biopsy core position was recorded in 3 dimensions with documentation of location of each positive biopsy core, Gleason score, percentage of involvement of each core, and presence/absence of perineural invasion. RESULTS: Mean pre-TRUS prostate specific antigen was 4.7 ng/mL with a Gleason score of 6 involving a median of 5% of 1 TRUS core. The mean number of TTMB biopsy cores was 58.5, with 6.6 cores positive for malignancy. Ten patients had clinically insignificant prostate cancer (15.7%), 8 had no TTMB-detected cancer (12.5%), and 46 (71.9%) had clinically significant cancer. Of patients with cancer, 37 (66.1%) had bilobar involvement and 25 (44.6%) harbored a Gleason score of ≥7. In a multivariate analysis, tobacco consumption was found to be most closely related to clinically significant disease on TTMB. CONCLUSIONS: TRUS biopsy underestimates disease extent and Gleason score in some patients. TTMB provides a more accurate assessment of the presence of aggressive histology.

Gleason score 7 prostate cancer treated with interstitial brachytherapy with or without supplemental external beam radiation and androgen deprivation therapy: is the primary pattern on needle biopsy prognostic?

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.

Time to failure after definitive therapy for prostate cancer: implications for importance of aggressive local treatment.

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 brachytherapy 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 D90 was 119% and V100 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 non-prostate 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 high-risk 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 presence of micrometastatic disease prior to treatment is rare, even in high risk patients.

Patient-reported long-term rectal function after permanent interstitial brachytherapy for clinically localized prostate cancer.

PURPOSE: To evaluate the effect of permanent interstitial brachytherapy with or without supplemental therapies on long-term rectal function using a patient-administered quality-of-life instrument. METHODS AND MATERIALS: One hundred thirty four of the initial 219 prostate brachytherapy patients who remain alive and have participated in a prospective evaluation of rectal function were mailed the rectal function assessment score (R-FAS). Of the 134 patients, 3 have a colostomy because of colorectal cancer, 2 failed to respond, and 129 (99.2% of eligible patients) returned a completed R-FAS. R-FAS ranges from 0 to 27 with lower scores indicative of better bowel function. Median followup was 14 years. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on bowel function. RESULTS: For the current cohort, R-FAS was 3.35, which was comparable to the 1999 (4.29), 2002 (3.92), and 2006 (4.00) surveys. In the 2011 survey, 10 (7.8%), 17 (13.1%), and 102 (78.3%) patients reported bowel function to be worse, improved, or unchanged after brachytherapy. No patient has developed a rectal ulcer or fistula. The number of preimplant bowel movements, tobacco, and diabetes mellitus correlated with R-FAS. Consistent with the previous thee surveys, patient's perception of overall rectal quality of life was inversely related to the use of supplemental external beam radiation. CONCLUSIONS: Long-term rectal function after prostate brachytherapy is favorable with a small number of patients reporting deterioration in bowel function. The judicious use of supplemental external beam radiation with particular attention to rectal doses may further improve long-term function.

Prognostic importance of small prostate size in men receiving definitive prostate brachytherapy.

PURPOSE: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. METHODS AND MATERIALS: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size (≤ 20 cm(3)) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. RESULTS: Median prostate size for the entire cohort was 32.7 cm(3). For the 167 men with small prostates, median prostate size was 17.4 cm(3). There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. CONCLUSION: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.

Prognostic importance of tobacco use in men receiving definitive prostate brachytherapy.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: Current smokers presented with a lower body mass index (p<0.001), smaller prostate size (p=0.003), younger age (p<0.001), 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 (p<0.001) 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 (p<0.001). There was no association between smoking and any prostate cancer-specific outcome. CONCLUSIONS: Smokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers.

Long-term outcome for very high-risk prostate cancer treated primarily with a triple modality approach to include permanent interstitial brachytherapy.

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) >20ng/mL, any clinical stage T3, or any PSA >40ng/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 D(90) (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 11.0ng/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.

Serum testosterone kinetics after brachytherapy for clinically localized prostate cancer.

PURPOSE: To evaluate temporal changes in testosterone after prostate brachytherapy and investigate the potential impact of these changes on response to treatment. METHODS AND MATERIALS: 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. RESULTS: 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 (p < 0.001), 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). CONCLUSION: 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.

Distant metastases following permanent interstitial brachytherapy for patients with clinically localized prostate cancer.

PURPOSE: Recent publications have suggested high-risk patients undergoing radical prostatectomy have a lower risk of distant metastases and improved cause-specific survival (CSS) than patients receiving definitive external beam radiation therapy (XRT). To date, none of these studies has compared distant metastases and CSS in brachytherapy patients. In this study, we evaluate such parameters in a consecutive cohort of brachytherapy patients. METHODS AND MATERIALS: From April 1995 to June 2007, 1,840 consecutive patients with clinically localized prostate cancer were treated with brachytherapy. Risk groups were stratified according to National Comprehensive Cancer Network (www.nccn.org) guidelines. Subgroups of 658, 893, and 289 patients were assigned to low, intermediate, and high-risk categories. Median follow-up was 7.2 years. Along with brachytherapy implantation, 901 (49.0%) patients received supplemental XRT, and 670 (36.4%) patients received androgen deprivation therapy (median duration, 4 months). The mode of failure (biochemical, local, or distant) was determined for each patient for whom therapy failed. Cause of death was determined for each deceased patient. Multiple parameters were evaluated for impact on outcome. RESULTS: For the entire cohort, metastases-free survival (MFS) and CSS at 12 years were 98.1% and 98.2%, respectively. When rates were stratified by low, intermediate, and high-risk groups, the 12-year MFS was 99.8%, 98.1%, and 93.8% (p < 0.001), respectively. CSS rates were 99.8%, 98.0%, and 95.3% (p < 0.001) for low, intermediate, and high-risk groups, respectively. Biochemical progression-free survival was 98.7%, 95.9% and 90.4% for low, intermediate, and high-risk patients, respectively (p < 0.001). In multivariate Cox-regression analysis, MFS was mostly closely related to Gleason score and year of treatment, whereas CSS was most closely associated with Gleason score. CONCLUSIONS: Excellent CSS and MFS rates are achievable with high-quality brachytherapy for low, intermediate, and high-risk patients. These results compare favorably to alternative treatment modalities. In particular, our MFS and CSS rates for high-risk patients appear superior to those of published radical prostatectomy series.

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy.

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 < 0.001). Cardiovascular events accounted for a significant portion of deaths in each IIEF-6 group. When combined with other risk factors for cardiovascular disease, an IIEF-6 score of ≤12 had an additive effect on all-cause mortality (IIEF-6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%). CONCLUSIONS: A pre-implant IIEF-6score of ≤12 was associated with a higher incidence of all-cause mortality. Pre-treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients. Aggressive treatment of medical co-morbidity is warranted to impactOS.