American Brachytherapy Society Task Group Report: Combination of brachytherapy and external beam radiation for high-risk prostate cancer.

PURPOSE: To review outcomes for high-risk prostate cancer treated with combined modality radiation therapy (CMRT) utilizing external beam radiation therapy (EBRT) with a brachytherapy boost. METHODS AND MATERIALS: The available literature for high-risk prostate cancer treated with combined modality radiation therapy was reviewed and summarized. RESULTS: At this time, the literature suggests that the majority of high-risk cancers are curable with multimodal treatment. Several large retrospective studies and three prospective randomized trials comparing CMRT to dose-escalated EBRT have demonstrated superior biochemical control with CMRT. Longer followup of the randomized trials will be required to determine if this will translate to a benefit in metastasis-free survival, disease-specific survival, and overall survival. Although greater toxicity has been associated with CMRT compared to EBRT, recent studies suggest that technological advances that allow better definition and sparing of critical adjacent structures as well as increasing experience with brachytherapy have improved implant quality and the toxicity profile of brachytherapy. The role of androgen deprivation therapy is well established in the external beam literature for high-risk disease, but there is controversy regarding the applicability of these data in the setting of dose escalation. At this time, there is not sufficient evidence for the omission of androgen deprivation therapy with dose escalation in this population. Comparisons with surgery remain limited by differences in patient selection, but the evidence would suggest better disease control with CMRT compared to surgery alone. CONCLUSIONS: Due to a series of technological advances, modern combination series have demonstrated unparalleled rates of disease control in the high-risk population. Given the evidence from recent randomized trials, combination therapy may become the standard of care for high-risk cancers.

Fifteen-year biochemical relapse-free survival, cause-specific survival, and overall survival following I(125) prostate brachytherapy in clinically localized prostate cancer: Seattle experience.

PURPOSE: To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I(125) brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience. METHODS AND MATERIALS: Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I(125) monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots. RESULTS: Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups. CONCLUSION: I(125) monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.

Effects of the time interval between prostate brachytherapy and postimplant dosimetric evaluation in community practice: analysis of the Pro-Qura database.

OBJECTIVE: To evaluate the influence of postimplant dosimetric timing on prostate brachytherapy quality in community practice. MATERIALS AND METHODS: The Pro-Qura database was stratified by multiple time intervals between the implant and postimplant dosimetric analysis. Postimplant dosimetry was performed in a standardized fashion. Criteria for implant adequacy included V(100) >80%, D(90) >90%, and V(150) <60% for I-125 and <75% for Pd-103. Implants with V(100) <80% and D(90) <90% were deemed "too cool." Implants were considered "too hot" if D(90) >140% of prescription dose and/or V(150) >150% for I-125 and >75% for Pd-103. RESULTS: For I-125, the average V(100) and D(90) increased from 88.6% to 89.8%, and 102.8% to 103.1% for day 0 and day 30 dosimetry. For Pd-103 implants the change was more pronounced, with V(100) and D(90) increasing from 81.6% to 87.8% (P < 0.001) and 88.7% to 100.0% (P < 0.001) for day 0, and day 30, respectively. The percentage of implants considered too cool based on a V(100) and D(90) criteria decreased from 18.8% and 26.9% on day 0 to 11.0% and 19.7% on day 30, respectively. Implants determined to be too hot based on a V(150) >60% (I-125)/>75% (Pd-103) or D(90) >140% were 16.4% and 2.2% on day 0 and 16.0% and 0.7% on day 30, respectively. CONCLUSION: In community-based brachytherapy programs, postimplant dosimetry performed at day 30 resulted in a statistically and clinically significant improvement in postimplant dosimetry compared with day 0. The influence of timing is substantially greater for Pd-103 than I-125.

Influence of Pro-Qura-generated plans on postimplant dosimetric quality: a review of a multi-institutional database.

The influence of Pro-Qura-generated plans vs. community-generated plans on postprostate brachytherapy dosimetric quality was compared. In the Pro-Qura database, 2933 postplans were evaluated from 57 institutions. A total of 1803 plans were generated by Pro-Qura and 1130 by community institutions. Iodine-125 (125I) plans outnumbered Palladium 103 (103Pd) plans by a ratio of 3:1. Postimplant dosimetry was performed in a standardized fashion by overlapping the preimplant ultrasound and the postimplant computed tomography (CT). In this analysis, adequacy was defined as a V100 > 80% and a D90 of 90% to 140% for both isotopes along with a V150 < 60% for 125I and < 75% for 103Pd. The mean postimplant V100 and D90 were 88.6% and 101.6% vs. 89.3% and 102.3% for Pro-Qura and community plans, respectively. When analyzed in terms of the first 8 sequence groups (10 patients/sequence group) for each institution, Pro-Qura planning resulted in less postimplant variability for V100 (86.2-89.5%) and for D90 (97.4-103.2%) while community-generated plans had greater V100 (85.3-91.2%) and D90 (95.9-105.2%) ranges. In terms of sequence groups, postimplant dosimetry was deemed "too cool" in 11% to 30% of cases and "too hot" in 12% to 27%. On average, no clinically significant postimplant dosimetric differences were discerned between Pro-Qura and community-based planning. However, substantially greater variability was identified in the community-based plan cohort. It is possible that the Pro-Qura plan and/or the routine postimplant dosimetric evaluation may have influenced dosimetric outcomes at community-based centers.

Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States.

PURPOSE: This study is aimed at understanding and defining the current patterns of care with respect to prostate brachytherapy for patients with intermediate-risk localized disease in the combined academic and community setting. METHODS AND MATERIALS: A nomogram-based survey was developed at the Seattle Prostate Institute defining the accepted criteria for intermediate-risk prostate cancer. Patients were defined as having intermediate-risk prostate cancer if they met one of the following criteria: prostate-specific antigen (PSA) >10 ng/dL, Gleason score (GS) > or = 7, or cT2b or cT2c disease. Additional potential predictive factors including perineural invasion (PNI), GS 3+4 vs. 4+3, and high-volume disease were included. RESULTS: In the absence of PNI, all of those surveyed would perform monotherapy for intermediate-risk patients, GS 7 (3+4) or PSA 10-20, with cT1c and <30% cores +. Up to 80% would perform monotherapy for patients with cT1c, GS 7 (4+3), and <30% cores +. Eighty to 90% of physicians would perform an implant alone with cT2a and either a PSA of 10-20 or GS of 7 (3+4) and <30% cores +. Fifty to 60% of those surveyed stated that they would treat a patient with cT2b disease, GS 7 (3+4), or PSA 11-20, with less than two-thirds of the biopsy cores positive in the absence of PNI. CONCLUSIONS: This Patterns of Care (POC) study reveals that certain subsets of intermediate-risk localized prostate cancer patients are considered appropriate candidates for an interstitial implant alone.

Initial analysis of Pro-Qura: a multi-institutional database of prostate brachytherapy dosimetry.

PURPOSE: The study aimed to analyze the Pro-Qura database in terms of patient implant sequence number for each institution to determine evidence for a dosimetric learning curve. METHODS AND MATERIALS: In the Pro-Qura database, 2833 of a total of 4614 postplans from 57 brachytherapists were analyzed for evidence of a dosimetric learning curve. The median time between implant and postimplant CT scan was 30 days. I-125 was used in 2123 patients (1687 monotherapy and 536 boost) and Pd-103 in 710 patients (367 monotherapy and 343 boost). Preimplant prostate volume was 35.3 and 32.9 cm3 in the I-125 and Pd-103 cohorts, respectively. The mean I-125 seed activity was 0.32 and 0.26 mCi for monotherapy and boost, whereas for Pd-103 the mean seed activity was 1.59 and 1.27 mCi, respectively. Postimplant dosimetry was performed in a standardized fashion by overlaying the preimplant ultrasound and the postimplant CT scan. Criteria for implant adequacy included a D90 >90% and a V100 >80% for both isotopes. An adequate V150 was defined as <60% for I-125 and <75% for Pd-103. RESULTS: The mean V100 and D90 were 88.9% and 101.9% of prescription dose, respectively. When analyzed in terms of patient sequence number for each institution, the mean V100 for the first 10 patients was 87.4% and increased to 88.6% for patients 11-20 (p = 0.036). Similarly, the mean D90 for the first 10 patients was 98.9%, whereas for the second cohort of 10 patients the mean D90 increased to 102.2% (p = 0.001). In terms of mean V100 and D90, there was minimal further change for subsequent 10 patient institutional groupings of patient sequence numbers. For the first 10 cases, 27.2% were deemed "too cool" (V100 <80% and/or D90 <90%). Approximately 16% of all implants were deemed "too hot" (D90 >140% or V150 >60% for I-125 or >75% for Pd-103). CONCLUSIONS: Although a learning curve exists for prostate brachytherapy, high-quality brachytherapy is achievable in approximately 75-80% of patients treated at community centers.

15-Year biochemical relapse free survival in clinical Stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience.

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

Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation.

PURPOSE: To assess long-term prostate-specific antigen (PSA) outcome after permanent prostate brachytherapy (BT) and identify predictors of improved disease-free survival. METHODS AND MATERIALS: Eleven institutions combined data on 2,693 patients treated with permanent interstitial BT monotherapy for T1-T2 prostate cancer. Of these patients, 1,831 (68%) were treated with I-125 (median dose, 144 Gy) and 862 (32%) were treated with Pd-103 (median dose, 130 Gy). Criteria for inclusion were: available pre-BT PSA, BT > or =5 years before data submission, BT between 1988-1998, and no androgen deprivation before failure. The median follow-up was 63 months. RESULTS: Among patients where the I-125 dose to 90% of the prostate (D90) was > or =130 Gy, the 8-year PSA relapse-free survival (PRFS) was 93% compared with 76% for those with lower D90 dose levels (p < 0.001). A multivariable analysis identified tumor stage (p = 0.002), Gleason score (p < 0.001), pretreatment PSA level (p < 0.001), treatment year (p = 0.001), and the isotope used (p = 0.004) as pretreatment and treatment variables associated with PRFS. When restricted to patients with available postimplantation dosimetric information, D90 emerged as a significant predictor of biochemical outcome (p = 0.01), and isotope was not significant. The 8-year PRFS was 92%, 86%, 79%, and 67%, respectively, for patients with PSA nadir values of 0-0.49, 0.5-0.99, 1.0-1.99, and >2.0 ng/mL (p < 0.001). Among patients free of biochemical relapse at 8 years, the median nadir level was 0.1 ng/mL, and 90% of these patients achieved a nadir PSA level <0.6 ng/mL. CONCLUSIONS: Outcome after permanent BT for prostatic cancer relates to tumor stage, Gleason score, pretreatment PSA, BT year, and post-BT dosimetric quality. PSA nadir < or =0.5 ng/mL was particularly associated with durable long-term PSA disease-free survival. The only controllable factor to impact on long-term outcome was the D90 which is a reflection of implant quality.

Second malignancies after prostate brachytherapy: incidence of bladder and colorectal cancers in patients with 15 years of potential follow-up.

PURPOSE: To report the incidence of second bladder and colorectal cancers after prostate brachytherapy. METHODS AND MATERIALS: This review included 125 patients treated with I-125 brachytherapy alone, and 223 patients who received supplemental external beam radiation therapy. Median follow-up was 10.5 years. Patients were followed for the development of lower genitourinary and colorectal cancers. Second malignancies arising five years after radiation therapy were defined as being potentially associated with treatment; observed rates were then compared with age-matched expected rates according to Surveillance, Epidemiology, and End Results data. RESULTS: Five years out of treatment, there were 15 patients with a second solid tumor, including bladder cancer (n = 11), colorectal cancer (n = 3), and prostatic urethra cancer (n = 1). The incidence of second malignancy was no different in patients treated with brachytherapy alone (1.6%) vs. those receiving external beam radiotherapy (5.8%, p = 0.0623). There were more observed bladder cancers compared with those expected (relative risk, 2.34, 95% confidence interval 0.96-3.72; absolute excess risk 35 cancers per 10,000 patients). Relative risk did not significantly change over increasing follow-up intervals up to 20 years after treatment. CONCLUSIONS: There may be an increased but small risk of developing a second malignancy after radiation therapy for prostate cancer. This outcome could be related to radiation carcinogenesis, but more vigilant screening and thorough workup as a result of radiation side effects and predisposing conditions (e.g., genetic and environmental factors) in many of the patients found to have second malignancies likely contributed to the higher number of observed malignancies than expected.

Permanent prostate brachytherapy: is supplemental external-beam radiation therapy necessary?

Permanent prostate brachytherapy with or without supplemental therapies is a highly effective treatment for clinically localized prostate cancer, with biochemical outcomes and morbidity profiles comparing favorably with competing local modalities. However, the absence of prospective randomized brachytherapy trials evaluating the role of supplemental external-beam radiation therapy (XRT) has precluded the development of evidence-based treatment algorithms for the appropriate inclusion of such treatment. Some groups advocate supplemental XRT for all patients, but the usefulness of this technology remains largely unproven and has been questioned by recent reports of favorable biochemical outcomes following brachytherapy used alone in patients at higher risk. Given that brachytherapy can be used at high intraprostatic doses and can obtain generous periprostatic treatment margins, the use of supplemental XRT may be relegated to patients with a high risk of seminal vesicle and/or pelvic lymph node involvement. Although morbidity following brachytherapy has been acceptable, supplemental XRT has shown an adverse impact on long-term quality of life. The completion of ongoing prospective randomized trials will help define the role of XRT as a supplement to permanent prostate brachytherapy.

Comparison of biochemical failure definitions for permanent prostate brachytherapy.

PURPOSE: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1-T2 prostate cancer treated by permanent prostate brachytherapy. METHODS AND MATERIALS: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1-T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure. RESULTS: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1-3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit. CONCLUSIONS: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable.

Factors that predict treatment choice and satisfaction with the decision in men with localized prostate cancer.

PURPOSE: Men diagnosed with localized prostate cancer (LPC) often have the opportunity to participate in the treatment choice. The purpose of this study was to evaluate relationships between influential factors on treatment choice and the decision-related outcomes of decisional conflict and satisfaction. PATIENTS AND METHODS: This report presents data from 260 men diagnosed with LPC who were identified by their clinicians as having a choice of treatments. Men completed questionnaires at home within 2 weeks of the informational clinic visit with the clinician, but before treatment. The respondent sample had a mean age of 63.2 years (standard deviation, 8.1 years); the majority were married/partnered (82.7%), working (51.5%), white (93.8%), and educated at the collegiate level (83.8%). Personal factors (information, influential people, and outcomes), treatment choice, and decisional conflict and satisfaction with the decision (SWD) were queried. Relationships between all variables and the outcomes, SWD, and treatment choice were explored using exhaustive chi(2) automatic interaction detector. RESULTS: The strongest predictor partition variable for SWD was the subscale "factors contributing to uncertainty" (adjusted P < 0.0001) followed by the Trait Anxiety score (adjusted P = 0.0388). The strongest predictive partition for the actual treatment choice was age group (adjusted P < 0.0001), followed by interacting marital status (adjusted P = 0.0003), influence of the urologist (adjusted P = 0.0008), and use of the Internet (adjusted P = 0.0479). Men with LPC were more satisfied with their treatment choice when they reported fewer uncertainty factors; these are factors mainly relevant to information needed to understand the pros and cons and to make a decision. Consistent with this finding for treatment choice is the use of the Internet, though this factor interacted with age, the influence of their surgeon, and marital status. CONCLUSION: This study suggests that personally meaningful information communicated between patients and clinicians is paramount.

Variability of prostate brachytherapy pre-implant dosimetry: a multi-institutional analysis.

PURPOSE: To conduct a multi-institutional comparison of prostate brachytherapy pre-implant dosimetry of Pd-103 and I-125. METHODS AND MATERIALS: Eight experienced brachytherapists submitted Pd-103 and I-125 monotherapeutic and boost pre-implant dosimetry plans for central review. All 32 plans were calculated using the same transrectal ultrasound volumetric study. Seeds of any strength were acceptable, but were restricted to Theraseed Model 200 (Theragenics Inc., Buford, GA) and Oncura Oncoseed Model 6711 (Oncura, Plymouth Meeting, PA). The dosimetric analysis included evaluation of target volume, target to prostate ratio, target length, number of needles, seed activity, number of seeds, total activity, total activity divided by treatment planning volume, the use of extracapsular seeds, and average treatment margins (defined as the perpendicular distance between the prostate capsule and the 100% isodose line). Prostate coverage was defined in terms of V(100)/V(150)/V(200)/V(300) and D(100)/D(90)/D(50), whereas urethral dosimetry consisted of UV(100)/UV(150)/UV(200) and UD(90)/UD(50). RESULTS: The mean planning target volume to prostate volume ratio varied dramatically (mean 1.29, range 0.99-1.76) with the target length ranging from 3.5 to 4.5 cm. Although the prostate V(100) was >95% in all cases, the V(150) ranged from 29.9% to 92.1% and the V(200) from 6.72% to 52.5%. The urethral V(100) was 100% in all cases with six of the eight brachytherapists limiting the UV(150) to <3%. However, the median urethral dose varied by up to 50%. Treatment margins also varied significantly (average 3.98 mm, range 0.32-7.68 mm). All brachytherapists used extracapsular seeds with five implanting >25% of the seeds in extracapsular locations (range 6.4-58.2%). In addition, significant variability existed in the number of needles, number of seeds, and seed strength. CONCLUSIONS: This study highlights the substantial variability that exists regarding target volume, seed strength, dose homogeneity, treatment margins, and extracapsular seed placement, although prostate brachytherapy prescription doses are uniform. The standardization of pre-implant dosimetry is essential for meaningful multi-institutional comparisons of biochemical outcomes and morbidity.

Technical improvement in permanent seed implantation: a two-stage brachytherapy system. Description and comparison with current technique.

PURPOSE: Permanent seed implantation by available techniques has modest limitations. A new, two-stage needle design and technique is described and evaluated in comparison to a conventional permanent seed technique. METHODS AND MATERIALS: The technique involves placing a stylet and sleeve initially into the all target coordinates prior to seed placement similar to temporary seed technique. The second stage involves consecutively removing the stylet from each sleeve and inserting a clear, plastic needle containing preloaded seeds into the sleeve and implanting the seeds. Fifty-six (125)I patients were treated with the two-stage technique. Comparisons were made with a cohort of 71 patients implanted using a conventional technique at the Seattle Prostate Institute. Prostate movement, surgical time, catheterization rate, and DVH postop dosimetry were analyzed. RESULTS: After an initial learning curve, the two-stage technique had surgical times similar to conventional techniques. Cephalad movement of 3-10 mm was noted in 4 (8%) patients vs. 71 (100%) patients with our conventional technique. Of the 6 (10%) patients who required Foley catheterization, 3 (5%) did so for 1 day and 3 (5%) did so for less than 3 weeks. Day 1 CT scan based dosimetry was calculated on all patients. The V100 ranged from 80-100% with a median of 92.5%. For primary cases, the V100 (<85%) was 14% for the conventional vs. 7% for the two-stage technique. No two-stage patient had a V100 <80%. The V100 values for the two-stage and conventional techniques demonstrated a possible advantage with the two-stage technique (mean V100 92.6% vs. 90.7%, [p=0.051]). The D90 for the two-stage technique ranged from 123-190 Gy with a median of 151.5 Gy for implant only and a median of 127 Gy for boost cases. The D90 values for the two-stage patients were slightly but not statistically better than the conventional technique (p=0.232). Thirty-one percent of conventional technique patients had a D90 <140 Gy vs. 22% for two-stage technique. CONCLUSION: This new two-stage brachytherapy technique may offer some advantages over conventional techniques including: simple and improved needle loading verification, less complicated and better visualization of needle placement, improved stabilization of the gland, and more consistent postoperative dosimetry.

Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: the Seattle experience.

PURPOSE: The role of external beam radiation therapy in addition to brachytherapy continues to be scrutinized for long term control of PSA levels after prostate cancer diagnosis. METHODS AND MATERIALS: We report 10-year biochemical relapse-free survival (BRFS) on 232 patients presenting with localized prostate cancer and consecutively treated with iodine(125) (I(125)) or palladium(103) (Pd(103)) brachytherapy and neoadjuvant external beam radiation therapy. Multivariate regression analysis was used to create a pretreatment clinical prognostic risk model using a modified ASTRO consensus definition (two consecutive rises in serum PSA) as the outcome. Gleason scoring was performed by pathologists at a small community hospital. Derived risk categories are the following: low = PSA 10 ng/mL or Gleason Score >or=7 or stage >or=T2c (1 intermediate risk factor); and high = 2 or more intermediate risk factors. Time to PSA failure (local, distant, or biochemical) was calculated and compared using Kaplan-Meier plots. RESULTS: Ten-year BRFS for the entire treatment group was 70%. Biochemical control rates by risk cohort analysis (95% confidence interval): low risk, 85% (83.3-90.7%); intermediate risk, 77% (73.0-84.5%); and high risk, 45% (45.4-57.2%). Using a risk grouping proposed by the Mt. Sinai group, the BRFS was: low risk, 84%; intermediate risk, 93%; and high risk, 57%. Grouping by the risk classification used by D'Amico, the BRFS was: low risk, 86%; intermediate risk, 90%; and high risk, 48%. CONCLUSIONS: I(125) or Pd(103) brachytherapy, as a boost combined with EBRT, continues to result in high rates of biochemical control at 10 years. Different risk group classification schemes lead to different BRFS results.

Adjuvant chemohormonal therapy of high risk prostate carcinoma. Ten year results.

BACKGROUND: Patients with T3 and/or N1 prostate carcinoma have poor cure rates. The authors sought to improve the relapse free, cancer specific survival of these patients by adding chemohormonal therapy to radiation. METHODS: Twenty-five men with clinical Stage III positive seminal vesicles or positive nodes received six courses of vinblastine, doxorubicin, and mitomycin with simultaneous radiation and permanent androgen deprivation. Prostate specific antigen (PSA) testing was the sole criterion for relapse. Median followup was 10.5 years. RESULTS: Treatment was well tolerated. Patients received 91-95% of each drug and all planned radiation. At 10 years the cumulative relapse free rate determined by continuously undetectable PSA levels was 73%, and the cumulative cancer specific survival was 81%. Of node-positive patients, 82% were relapse-free at 10 years. CONCLUSIONS: The addition of chemotherapy to hormonal and radiation therapy is feasible and is accepted by most men when they are openly informed of their prognosis with conventional therapy. Results in the current small series appear excellent and may be superior to radiation plus hormones alone. Larger randomized studies are warranted.

Risk factors for acute urinary retention requiring temporary intermittent catheterization after prostate brachytherapy: a prospective study.

PURPOSE: We prospectively investigated prognostic factors for men undergoing transperineal radioactive seed implantation for prostate cancer at the University of Washington. METHODS AND MATERIALS: Between February and April, 1998, 62 consecutive unselected patients were prospectively followed after brachytherapy for early-stage prostate adenocarcinoma. Pretreatment variables included age, American Urological Association (AUA) score, uroflowimetry, and prostate volume by ultrasound. Nonrandomized variables included hormonal therapy, seed type, and use of pelvic radiotherapy. Patients were contacted by phone at one week postoperatively and at one-month intervals thereafter. Follow-up continued until all patients provided the date of last catheterization. RESULTS: Urinary retention rate at one week was 34% (21 of 63 patients). At one month, 29%; at three months, 18%; and at six months, 10%. Preoperative flow rate and post-void residual did not predict for retention (p =.48 and p =.58). Use of alpha blockers, hormonal therapy, type of seed (103Pd or 1251), or external beam radiotherapy had no impact on risk of retention at any followup point. Preimplant volume and AUA score predicted for retention on univariate analysis, but on multivariate analysis only postimplant volume remained significant (p =.02) for predicting retention risk and duration. CONCLUSION: Patients with large prostate size (>36 g) and higher AUA score (>10) appear to be at greater risk of risk of retention as well as duration of retention as defined in our study. Further investigation will be needed to clarify the risk of urinary retention for men undergoing brachytherapy.