Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement.

PURPOSE: The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS: The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS: LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. CONCLUSIONS: LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.

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.

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.

The impact of diabetes mellitus on survival in men with clinically localized prostate cancer treated with permanent interstitial brachytherapy.

PURPOSE: Patients with cancer of any origin with preexisting diabetes mellitus (DM) are at increased risk for all-cause mortality compared with those without DM. However, the influence of DM on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) has not been clearly defined for men with clinically localized prostate cancer treated with brachytherapy. MATERIALS AND METHODS: From April 1995 to May 2006, 1624 consecutive patients underwent brachytherapy with or without supplemental therapies. A prebrachytherapy diagnosis of diabetes was present in 199 patients (12.3%). Median follow-up was 7.8 years. Cause of death was determined for each deceased patient. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. RESULTS: In patients without (n=1425) and with (n=199) DM, CSS was 97.2% versus 100% (P=0.168), bPFS was 95.6% versus 95.7% (P=0.960), and OS was 77.3% versus 56.0% at 12 years (P=0.003). In Cox regression analysis, OS in nondiabetic patients was most closely related to patient age, coronary artery disease, tobacco consumption, and androgen deprivation. In patients with diabetes, OS was related to patient age and coronary artery disease. In patients without diabetes, CSS was associated with Gleason score and clinical stage. No patient with diabetes died of prostate cancer. Patients with DM were more likely to die of cardiovascular disease (17.8% vs. 12.4%, P=0.007). CONCLUSIONS: DM does not impact CSS or bPFS after brachytherapy. OS is significantly lower in patients with diabetes due to more deaths from cardiovascular disease.

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.

Brachytherapy in men aged < or = 54 years with clinically localized prostate cancer.

OBJECTIVE: To report the biochemical progression-free survival (BPFS) in hormone-naive men aged < or = 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 < or = 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 < or = 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 < or = 54 years have a high probability of a good 8-year BPFS after permanent interstitial brachytherapy with or without supplemental EBRT.

Statins, especially atorvastatin, may improve survival following brachytherapy for clinically localized prostate cancer.

This is the largest and longest clinical study to date to examine statin usage and overall patient survival following clinically localized prostate cancer. In a retrospective examination of 938 consecutive patients with early-stage prostate cancer treated with brachytherapy, 191 patients were documented to be taking statin medications. The patients taking statin medications had significantly lower prostate-specific antigen values, percent positive biopsies, and prostate volume than those patients not taking statin medications. Statin usage resulted in a nonstatistical improvement in all survival parameters with the results most pronounced for atorvastatin. Improving prostate cancer survival with statins could have important treatment implications and could potentially limit or even improve the role of supplemental therapies. A prospective trial of statin medications in conjunction with definitive local treatment for prostate cancer is recommended.

The influence of isotope and prostate volume on urinary morbidity after prostate brachytherapy.

PURPOSE: 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. METHODS AND MATERIALS: 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 cohorts < or = 25 cm3, 25.1-35 cm3, 35.1-45 cm3, and >45 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. RESULTS: 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. CONCLUSIONS: 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.

Severity categories of the International Prostate Symptom Score before, and urinary morbidity after, permanent prostate brachytherapy.

OBJECTIVE: To determine if the International Prostate Symptom Score (IPSS) before seed implantation, stratified into mild (0-7), moderate (8-19) and severe (>20) categories, predicts brachytherapy-related morbidity in terms of IPSS resolution, catheter dependency and the need for surgical intervention after brachytherapy. PATIENTS AND METHODS: From January 1998 to September 2003, 1034 consecutive patients had permanent interstitial brachytherapy for clinical stage T1b-T3a NXM0 (2002 system) prostate cancer. Of the 1034 patients, 739 (71.5%) presented with an IPSS of 0-7, 287 (27.7%) of 8-19, and eight (0.8%) of > or = 20. The IPSS 8-19 cohort was further stratified into 8-14 (237 men) and 15-19 (50 men) subgroups. The median follow-up was 38.2 months. In all patients, an alpha-blocker was initiated before brachytherapy and continued at least until the IPSS normalized, the latter defined as a return to within 1 point of that before implantation. A median of 21 IPSS questionnaires were obtained per patient. Several clinical, treatment and dosimetric variables were evaluated as predictors of urinary morbidity. RESULTS: For the entire cohort, the IPSS peaked at a mean of 0.5 months after implantation and resolved at a mean of 1.7 months. At 5 years after brachytherapy, 90.1% of patients at risk (88.8%, 95.5%, and four of eight patients with a pre-implant IPSS of 0-7, 8-19 and > or = 20, respectively) were within the IPSS 0-7 category. Compared to the pre-implant IPSS, 13 patients (8%) were assigned to a higher IPSS severity category. Neither prolonged urinary catheter dependency (>5 days; 16 patients, 1.5%) or transurethral resection of the prostate (TURP, 17 patients, 1.6%) depended on the pre-implant IPSS subgroup. In Cox regression analysis, IPSS resolution was best predicted by pre-implant IPSS, prolonged catheter dependency by patient age, and TURP by any catheter dependency, the maximum IPSS increase and the maximum urethral dose. CONCLUSIONS: The IPSS before implantation predicted the resolution of IPSS after brachytherapy, but did not correlate with substantial urinary morbidity, including catheter dependency or the need for TURP. At 5 years after brachytherapy, 90.1% of patients at risk were assigned to the IPSS 0-7 category.

Statins, especially atorvastatin, may favorably influence clinical presentation and biochemical progression-free survival after brachytherapy for clinically localized prostate cancer.

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.

Influence of body mass index on biochemical outcome after permanent prostate brachytherapy.

OBJECTIVES: To evaluate the impact of body mass index (BMI) on the 8-year biochemical outcome after permanent prostate brachytherapy with or without the addition of supplemental external beam radiotherapy and/or androgen deprivation therapy (ADT). METHODS: From April 1995 through February 2001, 686 consecutive patients underwent brachytherapy using either palladium-103 or iodine-125 for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 59.5 months. The evaluated BMI subgroups were less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2. Biochemical progression-free survival was defined by a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after a nadir. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included BMI, patient age, clinical T stage, Gleason score, preimplant PSA level, risk group, percentage of positive biopsies, isotope, use of supplemental external beam radiotherapy, use of ADT, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose, minimal percentage of dose covering 90% of the target volume, tobacco use, and the presence of hypertension and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 95.8%, 95.6%, 94.1%, and 100% for patients in BMI categories less than 25, 25.0 to 29.9, 30.0 to 34.9, and 35 or more kg/m2, respectively. In hormone-naive and hormone-manipulated patients free of biochemical progression, the median post-treatment PSA level was less than 0.1 ng/mL. When integrated across risk groups and ADT use, BMI had no statistically significant impact on biochemical progression-free survival. At last follow-up, 5 patients (0.7%) had died of metastatic prostate cancer. In multivariate Cox regression analysis, pretreatment PSA level, Gleason score, clinical stage, percentage of positive biopsies, ADT use, and tobacco status, but not BMI, were statistically significant predictors of 8-year biochemical progression-free survival. CONCLUSIONS: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low, intermediate, and high-risk patients. When integrated across risk groups and hormonal status, BMI had no statistically significant influence on biochemical progression-free survival.

Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy.

PURPOSE: To evaluate the impact of supplemental external beam radiotherapy (EBRT) and/or androgen deprivation therapy (ADT) on 8-year biochemical outcome after permanent prostate brachytherapy. METHODS AND MATERIALS: Between April 1995 and January 2001, 668 consecutive patients underwent brachytherapy using either (103)Pd or (125)I for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) adenocarcinoma of the prostate gland. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 58.6 months. Biochemical progression-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included supplemental EBRT, ADT, patient age, clinical stage, Gleason score, preimplant prostate specific antigen (PSA), risk group, percentage of positive biopsies, isotope used, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of prescribed dose, minimal percentage of dose covering 90% of target volume, tobacco status, hypertension, and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 98.2%, 98.4%, and 88.2% for low-, intermediate-, and high-risk patients, respectively, with a median PSA level of <0.1 ng/mL for all risk groups and ADT and EBRT subgroups. At last follow-up, only 5 patients (0.8%) had died of metastatic prostate cancer. In multivariate analysis, Gleason score, percentage of positive biopsies, and ADT predicted for biochemical outcome in high-risk patients. In low- and intermediate-risk patients, none of the evaluated variables predicted for biochemical outcome. For the entire population, pretreatment PSA level, Gleason score, ADT, and clinical stage predicted for 8-year biochemical progression-free survival, with the percentage of positive biopsies approaching statistical significance. CONCLUSION: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low-, intermediate-, and high-risk patients. Although the role of supplemental EBRT could not be adequately evaluated in high-risk patients, it did not improve biochemical outcome in low- and intermediate-risk patients. However, ADT resulted in a statistically significant improvement in progression-free survival for high-risk patients.

Permanent interstitial brachytherapy in younger patients with clinically organ-confined prostate cancer.

OBJECTIVES: To evaluate biochemical progression-free survival in hormone-naive men 62 years of age or younger with clinically organ-confined prostate cancer who underwent brachytherapy with or without supplemental external beam radiotherapy. METHODS: From April 1995 through December 2000, 119 hormone-naive patients 62 years of age or younger underwent permanent interstitial brachytherapy for clinical T1b-T2cNxM0 (2002 American Joint Committee on Cancer) prostate cancer. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 5.4 years. Biochemical progression-free survival was defined by either a prostate-specific antigen (PSA) level of 0.4 ng/mL or less after a nadir or by the American Society for Therapeutic Radiology and Oncology consensus definition. No patient was lost to follow-up. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included age, clinical T stage, Gleason score, pretreatment PSA level, risk group, percentage of positive biopsies, isotope, supplemental external beam radiotherapy, prostate volume, brachytherapy planning volume, percentage of the target volume receiving 100%, 150%, and 200% of the prescribed dose, minimal percentage of the prescribed dose covering 90% of the target volume, and tobacco status. RESULTS: For the entire group, the actuarial 7-year biochemical progression-free survival rate was 96.1% and 98.3% for a PSA cutpoint of 0.4 ng/mL or less and for the American Society for Therapeutic Radiology and Oncology consensus definition, respectively. Using a PSA biochemical control definition of 0.4 ng/mL or less, 93.1%, 100%, and 95.2% of the low-risk, intermediate-risk, and high-risk hormone-naive patients were free of biochemical progression. The median post-treatment PSA level for the biochemically disease-free group was less than 0.1 ng/mL. In multivariate analysis, only the pretreatment PSA level predicted the biochemical outcome. CONCLUSIONS: Hormone-naive patients 62 years of age or younger have a high probability of 7-year biochemical progression-free survival after permanent interstitial brachytherapy with or without supplemental external beam radiotherapy.

Androgen deprivation-induced changes in prostate anatomy predict urinary morbidity after permanent interstitial brachytherapy.

PURPOSE: To evaluate the cytoreductive consequences of neoadjuvant androgen deprivation therapy on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after permanent interstitial brachytherapy. METHODS AND MATERIALS: A total of 116 patients (median follow-up, 30 months) with preandrogen and postandrogen deprivation therapy ultrasound studies and no history of preimplant transurethral resection of the prostate were evaluated. Androgen deprivation-induced changes in prostate volume, transition zone (TZ) volume, and urethral location were correlated with IPSS resolution, catheter dependency, and the need for postimplant surgical intervention. Prostate gland and TZ dimensions and volumes were measured by prolate ellipsoid calculation from the static ultrasound images. The urethral location was determined by identification of a urinary catheter. Additional clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment prostate-specific antigen, Gleason score, clinical T stage, preimplant IPSS, pre- and postandrogen deprivation ultrasound studies, treatment planning volume, supplemental external beam RT, isotope, total implant activity, Day 0 maximal dose received by 90% of the prostate gland, Day 0 percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose, and urethral dose. RESULTS: For hormonally manipulated patients, the prostate volume at implantation did not have a statistical influence on the percentage of patients returning to IPSS baseline, the time for IPSS normalization, the incidence of catheter dependency, the catheter-dependency time, or the need for postimplant surgical intervention. However, when compared with the hormone-naive cohort, hormonally manipulated patients were more likely to undergo postimplant surgical intervention (5.2% vs. 0.3%, p = 0.001). Greater androgen deprivation-induced reductions in prostate and TZ volumes, along with movement of the urethra closer to the posterior border of the prostate gland, resulted in a decreased incidence of postimplant urinary morbidity. Using Cox regression analysis, the time to IPSS resolution was best predicted by the percentage of TZ volume reduction. Stepwise linear regression analysis demonstrated that the catheter-dependency time was best predicted by the prehormonal therapy prostate volume, posthormonal therapy TZ volume, and the change in the urethral position; prolonged catheter dependency by the percentage of TZ volume reduction, prehormonal therapy TZ index, and the change in the urethral position; and the need for postimplant surgical intervention by the posthormonal therapy TZ index and the change in the urethral location. CONCLUSION: After neoadjuvant androgen deprivation therapy for volume reduction, some brachytherapy-related urinary morbidity parameters are highly related to the preandrogen deprivation prostate volume, variants in the TZ volume, and changes in the urethral location.

The effect of hormonal manipulation on urinary function following permanent prostate brachytherapy.

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 naïve, 227 received short-course cytoreductive (< or = 6 months) hormonal therapy, and 89 received extended (>6 months) hormonal therapy. An alpha-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 (#10878;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.

Effect of cigarette smoking on biochemical outcome after permanent prostate brachytherapy.

PURPOSE: Recent studies have suggested that cigarette smoking may be associated with an increased risk of death from prostate cancer. In this study, we evaluated the effect of cigarette smoking on the presentation and biochemical outcome after permanent prostate brachytherapy for prostate cancer. METHODS AND MATERIALS: A total of 582 patients underwent brachytherapy with generous periprostatic margins using either (103)Pd or (125)I with or without supplemental external beam radiotherapy between April 1995 and September 2000. Of the 582 patients, 178 (30.6%) had never smoked, 306 (52.6%) were former smokers, and 98 (16.8%) were current smokers. The median patient age was 67.9 years, and the median follow-up was 54.5 months. No patient was lost to follow-up. No patient underwent routine seminal vesicle biopsy or pathologic lymph node staging. The clinical, treatment, and dosimetric parameters evaluated included tobacco status, age, clinical stage, Gleason score, pretreatment prostate-specific antigen level, risk group, percentage of positive biopsies, ultrasound volume, isotope used, planning volume, hormonal status, use of external beam radiotherapy, and postimplant dosimetry (percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose and percentage of prescribed dose covering 90% of the target volume). Biochemical outcome was determined using the American Society for Therapeutic Radiology and Oncology consensus definition. RESULTS: No differences in the clinical, treatment, or dosimetric parameters were identified, except that current smokers were statistically younger than those who had never smoked or former smokers (65.9 vs. 67.8 vs. 68.3 years, respectively, p = 0.016). Specifically, no relationship was discerned between tobacco history and risk group, supplemental external beam radiotherapy, choice of isotope, or use of hormonal therapy. The overall biochemical freedom from progression survival rate at 7 years was 96.2%, 95.6%, and 91.6% for patients who had never smoked, former smokers, and current smokers, respectively (p = 0.126). When stratified by risk group and hormonal status, tobacco consumption did not predict outcome, although a trend for poorer biochemical progression-free survival was noted in current smokers. The median prostate-specific antigen level for hormone-naive and hormonally manipulated disease-free patients was <0.1 ng/mL. In multivariate Cox regression analysis, Gleason score, pretreatment prostate-specific antigen level, risk group, and hormonal status were predictors of biochemical outcome. CONCLUSION: In this prostate brachytherapy cohort, tobacco consumption did not predict for risk group stratification or treatment approach. Although no statistically significant difference was found in biochemical progression-free survival, a trend for poorer biochemical outcome was demonstrated in current smokers.

Effect of transurethral resection on urinary quality of life after permanent prostate brachytherapy.

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.

Extracapsular radiation dose distribution after permanent prostate brachytherapy.

The physical extent of the radiation therapy dose delivered to the periprostatic region was evaluated in 26 consecutive patients with low-risk prostate cancer (prostate-specific antigen or=5.0 mm for all slices evaluated. The utilization of preplanning periprostatic margins is strongly correlated with the administration of prescription radiation doses to the periprostatic region. The extent of the postimplant periprostatic margin (6.5 +/- 1.8 mm) satisfies the preplanning margin criterion of >5 mm.

Long-term urinary quality of life after permanent prostate brachytherapy.

PURPOSE: To evaluate late urinary function after permanent prostate brachytherapy using a validated, patient-administered quality-of-life instrument. METHODS AND MATERIALS: A total of 225 consecutive patients underwent prostate brachytherapy between April 1995 and March 1998. Of the 225 patients, 17 had died and 3 had been institutionalized secondary to Alzheimer's disease. Of the remaining 205 patients, each was mailed a self-administered questionnaire (the urinary function component of the Expanded Prostate Cancer Index [EPIC] and the International Prostate Symptom Score [IPSS]). Of the 205 surveys mailed, 195 (95.1%) were returned. The mean and median follow-up was 66.3 and 64.0 months, respectively. The clinical parameters evaluated included age, pretreatment prostate-specific antigen level, Gleason score, stage, risk group, prostate volume, presence of diabetes and hypertension, and tobacco consumption. The treatment parameters included the ultrasound planning volume, hormonal status, use of supplemental external beam radiotherapy, isotope, and follow-up. The dosimetric parameters included values of the minimal dose received by 90% of the prostate gland and the percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose. Because detailed baseline urinary function was not available, a cross-sectional survey was performed in which 51 newly diagnosed prostate cancer patients of comparable demographics served as controls. RESULTS: When the survey scores for the implant patients were compared with the control group, no significant differences in either the IPSS or function, bother, incontinence, or irritation/obstruction subscales of the urinary EPIC were discernible. In addition, no significant difference was observed between the implant and control groups when the EPIC and IPSS surveys were evaluated by each individual question. Of all the evaluated parameters, the use of tobacco was the best predictive variable for diminished quality of life. CONCLUSION: No significant difference was noted in the overall long-term urinary quality of life when brachytherapy patients were compared with a group of newly diagnosed prostate cancer patients of comparable demographics. Of all parameters evaluated, tobacco consumption was the single strongest predictor of late urinary function.

Prophylactic versus therapeutic alpha-blockers after permanent prostate brachytherapy.

OBJECTIVES: To evaluate the influence of prophylactic versus therapeutic alpha-blockers on urinary morbidity after permanent prostate brachytherapy. Multiple clinical and treatment parameters were evaluated to identify the factors associated with acute urinary morbidity. METHODS: A total of 234 consecutive patients underwent permanent prostate brachytherapy in one of two prospective randomized studies from October 1999 through February 2001 using either palladium-103 or iodine-125 for clinical Stage T1b-T2b (1997 American Joint Commission on Cancer staging system) prostate cancer at either the Schiffler Cancer Center or Puget Sound Health Care System. The mean and median follow-up was 8.8 +/- 4.6 months and 6 months, respectively. In 142 patients, an alpha-blocker was initiated before implantation and continued at least until the International Prostate Symptom Score (IPSS) returned to baseline levels; 92 patients either did not receive an alpha-blocker or received a therapeutic alpha-blocker after implantation because of urinary obstructive symptoms. The clinical and treatment parameters evaluated for urinary morbidity included prophylactic versus therapeutic alpha-blockers, age, preimplant IPSS, ultrasound volume, use of neoadjuvant hormones, use of supplemental external beam radiotherapy, isotope, urethral dose, and multiple dosimetric quality indicators (minimal dose received by 90% of the prostate gland and percentage of prostate volume receiving 100% or 200% of the prescribed minimal peripheral dose). Catheter dependency and the duration of alpha-blocker dependency were also evaluated. RESULTS: In both the prophylactic and the therapeutic cohorts, the IPSS peaked 1 month after implantation. Patients receiving a prophylactic alpha-blocker returned to baseline at a mean of 4 months and a median of 3 months postoperatively. For those patients not receiving prophylactic alpha-blockers, the IPSS returned to the antecedent value at a mean and median of 10 months and 6 months, respectively. Of the 125 patients receiving prophylactic alpha-blockers, 102 (81.2%) remained medication dependent at the conclusion of the study, and 140 (78.2%) of 179 patients receiving alpha-blockers other than for hypertensive purposes did so. The incidence of prolonged urinary catheter dependency (greater than 3 days) and the need for postimplant transuretheral incision of the prostate/transurethral resection of the prostate were not affected by alpha-blocker use. Cox regression analysis revealed that only the prophylactic use of alpha-blockers and the difference between the preimplant IPSS and the 1-month IPSS were predictive of the time to return to the referent zone. CONCLUSIONS: Prophylactic use of alpha-blockers results in significantly less urinary morbidity than either the absence or therapeutic use of alpha-blockers. In patients receiving prophylactic alpha-blockers, the IPSS normalized significantly faster but had no impact on urinary retention or the ultimate need for postimplant surgical intervention.