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.

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.

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.