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Purpose: Recently, new approaches have been implemented in treating patients with newly diagnosed metastatic prostate cancer (PCa). An interesting area of study is to determine which risk factors may be used as predictors of more aggressive PCa behavior in patients with biochemical failure. The aim of this study was to determine prognostic factors in patients with prostate-specific antigen (PSA) failure after undergoing brachytherapy., Methods and Materials: Between 1990 and 2015, 2771 patients with localized PCa underwent treatment at our institution treated by a single radiation oncologist with low-dose-rate brachytherapy as a component of definitive radiation therapy. Disease-specific survival (DSS), distant metastases (DM), and overall survival were calculated by the Kaplan-Meier method. Multivariable Cox regression analysis was also performed., Results: In this group, 2126 patients (89%) had no evidence of PSA failure. Of the 251 of patients that did have biochemical failure, 115 (45.8%), 58 (23.1%), 78 (31.1%) had a PSA doubling time (PSADT) of <6 months, 6-12 months, and >12 months, respectively. Doubling time was associated with a statistically significant impact on DSS and DM but not overall survival, which appears to be dominated by initial age at diagnosis as well as stage., Conclusions: We have shown here that PSADT predicts for DSS and freedom from DM in our large prospectively followed cohort. Given the variable trajectory of metastatic and recurrent PCa, strong prognostic factors such as PSADT may be able to select a group of patients who benefit from earlier or escalated systemic therapies such as androgen deprivation or cytotoxic chemotherapy., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We aimed to evaluate the impact of timing of androgen deprivation therapy (ADT) on survival in a cohort of patients with biochemical recurrence (BCR) after brachytherapy treatment for prostate cancer., Methods and Materials: We retrospectively identified 2366 men receiving permanent prostate brachytherapy with or without external beam radiation therapy. Patients experiencing BCR were stratified by receipt of immediate or delayed (≥3 months) ADT and prostate-specific antigen (PSA) failure threshold of 10 ng/mL. Prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) were evaluated using Fine-Gray's competing risks regression and Cox proportional hazard model, respectively., Results: We identified 109 patients in the study cohort treated with ADT for BCR, followed for a median of 11.4 years. Competing risk regression revealed that there was no difference in PCSM for patients receiving delayed vs. immediate ADT (hazard ratio [HR], 0.94; 95% confidence interval [CI]: 0.44-2.00: p = 0.871) or for those initiating hormonal therapy at PSA threshold of 10 vs. <10 ng/mL (HR, 0.85; 95% CI: 0.41-1.75; p = 0.649); similarly, there was no difference in ACM. PSA doubling time <6 months (HR, 2.52; 95% CI: 1.22-5.23; p = 0.013), time to BCR <3 years (HR, 3.27; 95% CI: 1.67-6.42; p = 0.003), and permanent prostate brachytherapy with external beam radiation therapy (HR, 5.21; 95% CI: 2.05-13.26; p = 0.001) were significantly associated with PCSM, as well as ACM., Conclusions: Among a cohort of brachytherapy patients, we identified no significant difference in survival for delayed salvage hormonal therapy. Shorter PSA doubling time and time to BCR are significantly associated with adverse outcomes, and these patients should be considered for immediate salvage therapy., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. A systematic review of randomised controlled trials (RCTs) of radiotherapy and other non-pharmacological management options for localised prostate cancer was undertaken., Methods: A search of thirteen databases was carried out until March 2014. RCTs comparing radiotherapy (brachytherapy (BT) or external beam radiotherapy (EBRT)) to other management options i.e. radical prostatectomy (RP), active surveillance, watchful waiting, high intensity focused ultrasound (HIFU), or cryotherapy; each alone or in combination, e.g. with adjuvant hormone therapy (HT), were included. Methods followed guidance by the Centre for Reviews and Dissemination and the Cochrane Collaboration. Indirect comparisons were calculated using the Bucher method., Results: Thirty-six randomised controlled trials (RCTs, 134 references) were included. EBRT, BT and RP were found to be effective in the management of localised prostate cancer. While higher doses of EBRT seem to be related to favourable survival-related outcomes they might, depending on technique, involve more adverse events, e.g. gastrointestinal and genitourinary toxicity. Combining EBRT with hormone therapy shows a statistically significant advantage regarding overall survival when compared to EBRT alone (Relative risk 1.21, 95% confidence interval 1.12-1.30). Aside from mixed findings regarding urinary function, BT and radical prostatectomy were comparable in terms of quality of life and biochemical progression-free survival while favouring BT regarding patient satisfaction and sexual function. There might be advantages of EBRT (with/without HT) compared to cryoablation (with/without HT). No studies on HIFU were identified., Conclusions: Based on this systematic review, there is no strong evidence to support one therapy over another as EBRT, BT and RP can all be considered as effective monotherapies for localised disease with EBRT also effective for post-operative management. All treatments have unique adverse events profiles. Further large, robust RCTs which report treatment-specific and treatment combination-specific outcomes in defined prostate cancer risk groups following established reporting standards are needed. These will strengthen the evidence base for newer technologies, help reinforce current consensus guidelines and establish greater standardisation across practices., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To identify predictors of metastatic disease after brachytherapy treatment for prostate cancer., Methods and Materials: All patients who received either brachytherapy alone (implant) or brachytherapy in combination with external beam radiation therapy for treatment of localized prostate cancer at The Mount Sinai Hospital between June 1990 and March 2007 with a minimum follow-up of 2 years were included. Univariate and multivariable analyses were performed on the following variables: risk group, Gleason score (GS), clinical T stage, pretreatment prostate-specific antigen level, post-treatment prostate-specific antigen doubling time (PSA-DT), treatment type (implant vs. implant plus external beam radiation therapy), treatment era, total biological effective dose, use of androgen deprivation therapy, age at diagnosis, and race. PSA-DT was analyzed in the following ordinate groups: 0 to 90 days, 91 to 180 days, 180 to 360 days, and greater than 360 days., Results: We included 1,887 patients in this study. Metastases developed in 47 of these patients. The 10-year freedom from distant metastasis (FFDM) rate for the entire population was 95.1%. Median follow-up was 6 years (range, 2-15 years). The only two significant predictors of metastatic disease by multivariable analyses were GS and PSA-DT (p < 0.001 for both variables). Estimated 10-year FFDM rates for GS of 6 or less, GS of 7, and GS of 8 or greater were 97.9%, 94.3%, and 76.1%, respectively (p < 0.001). Estimated FFDM rates for PSA-DT of 0 to 90 days, 91 to 180 days, 181 to 360 days, and greater than 360 days were 17.5%, 67.9%, 74%, and 94.8%, respectively (p < 0.001). Estimated 10-year FFDM rates for the low-, intermediate-, and high-risk groups were 98.6%, 96.2%, and 86.7%, respectively. A demographic shift to patients presenting with higher-grade disease in more recent years was observed., Conclusions: GS and post-treatment PSA-DT are both statistically significant independent predictors of metastatic disease. Patients with a high GS and/or short PSA-DT have a higher likelihood of developing metastatic disease and should be considered for systemic therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To measure the benefits of intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) when used in combination with brachytherapy for the treatment of prostate cancer., Methods and Materials: We conducted a retrospective review of all patients with localized prostate cancer who received external-beam radiotherapy (EBRT) in combination with brachytherapy with at least 1 year follow-up (n = 812). Combination therapy consisted of (103)Pd or (125)I implant, followed by a course of EBRT. From 1993 to March 2003 521 patients were treated with 3D-CRT, and from April 2003 to March 2009 291 patients were treated with IMRT. Urinary symptoms were prospectively measured with the International Prostate Symptom Score questionnaire with a single quality of life (QOL) question; rectal bleeding was assessed per the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. The Pearson χ(2) test was used to compare toxicities experienced by patients who were treated with either IMRT or 3D-CRT. Logistic regression analyses were also performed to rule out possible confounding factors., Results: Within the first 3 months after treatment, patients treated with 3D-CRT scored their urinary symptoms as follows: 19% mild, 44% moderate, and 37% severe; patients treated with IMRT scored their urinary symptoms as follows: 36% mild, 47% moderate, and 17% severe (p < 0.001). The 3D-CRT patients rated their QOL as follows: 35% positive, 20% neutral, and 45% negative; IMRT patients rated their QOL as follows: 51% positive, 18% neutral, and 31% negative (p < 0.001). After 1 year of follow-up there was no longer any difference in urinary morbidity between the two groups. Logistic regression confirmed the differences in International Prostate Symptom Score and QOL in the acute setting (p < 0.001 for both). Grade ≥ 2 rectal bleeding was reported by 11% of 3D-CRT patients and 7% of IMRT patients (p = 0.046); logistic regression analysis also confirmed this observation (p = 0.040)., Conclusions: When used in combination with brachytherapy, IMRT offers less Grade ≥ 2 rectal bleeding, less acute urinary toxicities, and is associated with a higher QOL compared with 3D-CRT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Understanding racial differences in disease presentation and response to therapy is necessary for the effective treatment and control of prostate cancer. In this study, the authors examined the influence of race on biochemical disease-free survival (BDFS) among men who received prostate brachytherapy., Methods: In total, 2301 men were identified who had a minimum follow-up of 24 months and had received low-dose-rate brachytherapy for prostate cancer at the Mount Sinai Medical Center from June 1990 to October 2008. Patient factors, with specific emphasis on patient race, were analyzed with respect to freedom from biochemical failure (FFbF). Kaplan-Meier analyses, life-tables, and log-rank tests were used to identify variables that were predictive of 10-year FFbF., Results: In this series, a total of 2268 patients included 81% Caucasians, 12% African Americans, 6% Hispanics, and 1% Asians. The 10-year actuarial FFbF rate was 70% for AA men and 84% for all others (P = .002). Between Caucasian men and AA men, the 10-year FFbF rate was 83% versus 70%, respectively (P = .001).There was no significant difference in 10-year FFbF between Caucasian men and Hispanic men (83% vs 86%, respectively; P = .6). The 10-year FFbF rate for Hispanic men and AA men was 86% versus 70%, respectively (P = .062). A greater percentage of AA men presented with higher prostate-specific antigen levels (PSA) (>10 ng/mL; 44% vs 21%; P < .001) and, thus, with higher risk disease (24% vs 15%; P < .001) compared with Caucasian men. Among the men with low-risk disease, the 10-year FFbF rate was 90% for Caucasian men and 76% for AA men (P = .041). The 10-year BDFS rate for patients who received brachytherapy alone was 86% for Caucasian men and 61% for AA men (P = .001); however, this difference was not observed when brachytherapy was combined with androgen-deprivation therapy(ADT) with or without supplemental external-beam radiotherapy (EBRT). Multivariate analysis revealed that PSA (P = .024), Gleason score (P < .001), the biologic effective dose (P < .001), EBRT (P = .002), ADT (P = .03), and AA race (P = .037) were significant predictors of 10-year FFbF. No significant differences was observed in overall survival, cause-specific survival, or distant metastasis-free survival between racial groups., Conclusions: AA race appeared to be an independent negative predictor of BDFS after prostate brachytherapy, and this result may highlight the need for more aggressive therapy in this patient population., (Copyright © 2011 American Cancer Society.)

Changes in morphologic patterns over a time course following radiation and their corresponding PSA levels were investigated. A total of 60 patients with prostatic adenocarcinoma treated with brachytherapy between 1993 and 2003, who had at least one positive post-radiation biopsy, were evaluated for their morphologic patterns as well as the associated PSA levels. A total of 86 positive post-radiation biopsies were performed. There were 17 patients with more than 1 positive post-radiation biopsy and 43 patients with single positive biopsy. Among the 17 with more than 1 positive biopsy, the morphologic patterns of treatment effect were commonly followed by patterns without treatment effect on subsequent biopsies. The morphology without treatment effect followed by treatment effect was infrequent. Furthermore, over a time course, the later the positive post-radiation biopsy, the much more common the morphologic pattern without treatment effect was observed. Compared to the morphologic pattern with treatment effect, the morphology without treatment effect was associated with a significantly higher PSA level (mean 0.69 versus 2.78 ng/ml, p<0.05). An increase in the Gleason's score in recurrent carcinoma was also noted in 14% of the cases. Multiple factors were likely involved in the variability of the changes in post-radiation morphologic patterns. A new neoplastic process was particularly considered in some of our cases, which may merit clinical attention. The significant difference in PSA levels between carcinomas without treatment effect and those with treatment effect also suggested a post-radiation variation of tumor biology and a potential role of these patterns in monitoring and managing the patients treated with brachytherapy.

Purpose: We analyzed the risk of urinary morbidity and incontinence in patients undergoing transurethral resection of the prostate (TURP) following prostate brachytherapy., Materials and Methods: A total of 2,050 patients underwent transperineal radioactive seed implantation of the prostate with or without external beam radiation therapy for the diagnosis of prostate cancer between June 1990 and February 2004. Of the 2,050 patients 38 (2%) underwent minimal (channel) TURP due to urinary symptoms or retention. Urinary morbidity was recorded prior to implantation and at followup intervals using the International Prostate Symptom Score and quality of life assessment scores. All patients underwent post-implantation computerized tomography based dosimetry at 1 month. The dose to 90% of prostate volume, prostate volume covered by 15% of the prescription dose and dose to 30% or 5 cm of urethral volume were recorded. Of the 38 patients 11 (29%) underwent Pd implantation alone and 12 (32%) received a partial (67%) Pd implant with external beam radiation therapy to a median dose of 45 Gy (range 41.4 to 59.4), while 15 (39%) underwent I implantation alone. Median followup after implantation was 38 months (range 2 to 97)., Results: Seven of the 38 patients (18%) undergoing TURP had urinary incontinence. Median time to TURP was 11 months (range 1 to 73). 25% Of patients who received an implant and external beam radiotherapy had urinary incontinence following TURP compared with 15% who underwent implantation alone (p = 0.26). There was no significant correlation between incontinence risk based on the dose to 90% of prostate volume (p = 0.32), the dose to 30% or 5 cm of urethral volume (p = 0.30) or prostate volume covered by 15% of the prescription dose (p = 0.36). Two of 24 patients (8%) who had underwent 2 years or less after implantation had urinary incontinence compared with 5 of 14 (36%) who underwent TURP greater than 2 years following implantation (p = 0.04)., Conclusions: Urinary incontinence developed in 18% of patients who underwent TURP following prostate brachytherapy. No significant correlations between radiation dose, preimplant prostate volume or hormonal therapy were identified with regard to this risk. Patients in late retention or with obstructive symptoms (greater than 2 years) following implantation who require TURP are at greater risk for incontinence.

Purpose: A prostate brachytherapy program was initiated in 1990, when comparatively little was known of the relative importance of disease- and treatment-related factors on outcome. Patients treated during the first 6 years of the program were analyzed to determine the value of patient selection and implant quality on biochemical control., Methods and Materials: We treated 243 patients with clinically localized prostate cancer with radioactive seed implantation and underwent 1-month CT-based dosimetric analysis. Follow-up ranged from 61 to 135 months (median 75). The Gleason score was < or =6 in 78% (n = 189), 7 in 14% (n = 35), and 8-10 in 8% (n = 19). The initial prostate-specific antigen (PSA) level was < or =10 ng/mL in 61% (n = 149), 10.1-20 ng/mL in 26% (n = 63), and >20 ng/mL in 13% (n = 31). The disease stage was T2a or less in 49% (n = 120), and Stage T2b-T2c in 51% (n = 123). A real-time ultrasound-guided technique was used with (125)I (n = 138) and (103)Pd (n = 105) isotopes. No patient underwent external beam radiotherapy as part of their primary treatment. Of the 243 patients, 60% also received hormonal ablation for at least 3 months before and 2-3 months after seed implantation. All patients included underwent a 1-month CT-based dosimetric analysis. The implant dose was defined as the dose delivered to 90% of the prostate volume on postimplant dosimetry (D(90)). On the basis of prior dose-response analyses, patients were retrospectively grouped into optimal D(90) ((125)I > or =140 Gy Task Group 43 or (103)Pd >/=100 Gy) and suboptimal D(90) ( (125)I <140 Gy or (103)Pd <100 Gy) dose groups. Biochemical failure was defined using the American Society for Therapeutic Radiology Oncology definition., Results: Disease-related factors, including initial PSA level, Gleason score, and stage, were significant predictors of biochemical failure. The actuarial 8-year freedom from biochemical failure (bFFF) rate was 80% for those with a PSA level < or =10 ng/mL, 86% for PSA 10.1-20 ng/mL, and 45% for PSA >20 ng/mL (p = 0.0019). Patients with a Gleason score of < or =6 had an 8-year bFFF rate of 81% vs. 67% for those with Gleason score 7 and 53% for those with Gleason score 8-10 (p = 0.0003). Patients with Stage T2a or less had an 8-year bFFF rate of 85% compared with 69% for those with Stage T2b-T2c (p = 0.013). The 8-year bFFF rate was 88% for low-risk patients (Stage T2a or less, Gleason score < or =6, and initial PSA level < or =10 ng/mL; n = 75), 81% for moderate-risk patients (Stage T2b or Gleason score 7 or initial PSA level >10.1-20 ng/mL; n = 70), and 65% for high-risk patients (two or more moderate-risk features or Gleason score > or =8 or initial PSA level >20 ng/mL; n = 98; p = 0.0009). Patients with optimal dose implants (n = 145) had an 8-year bFFF rate of 82% compared with 68% for those with suboptimal dose implants (n = 98; p = 0.007). Hormonal therapy did not significantly affect biochemical failure (p = 0.27). In multivariate analysis, the statistically significant variables included initial PSA level (p <0.0001), Gleason score (p = 0.024), and dose group (p = 0.046). Because our current practice limits implantation alone to low-risk patients, an analysis of this subgroup was undertaken to validate the importance of dose. In the optimal dose group, low-risk patients had an 8-year bFFF rate of 94% vs. 75% for the low-risk patients in the suboptimal dose group (p = 0.02)., Conclusion: With minimal follow-up of 5 years, these data continue to support the use of implantation alone in low-risk prostate cancer patients and demonstrate the importance of implant quality (dose) in achieving optimal outcomes. Low-risk patients who receive an optimal dose implant have a 94% bFFF rate at 8 years.

Objectives: The acute and chronic complications of permanent prostate brachytherapy are discussed., Materials and Methods: Review of literature for the complications associated with iodine-125 (125I) and palladium-103 (103Pd) prostate brachytherapy. Acute complications included urinary retention, changes in the International Prostate Symptom Score (IPSS) and need for TURP. Chronic morbidity included permanent urinary symptoms, incontinence, radiation proctitis and erectile dysfunction., Results: Urinary retention occurred in 1.5-22% of the patients postimplant. Acute urinary symptoms increased by over 100% 1 month after the procedure. By 12 months, the symptoms were either back to baseline or slightly elevated in over 90% of the patients. Significant obstructive symptoms or persistent urinary retention necessitating TURP occurred in 0-8.7%. Urinary incontinence was found in 0-19% treated by implant without associated TURP, in 0-85% for those who had a TURP prior to the implant and in 0-17% for those who had the TURP subsequent to the implant. Potency rates ranged from 34% to 86% 1-6 years postimplant. Radiation proctitis was found in 0.5-21.4%, with significant injury (fistula) occurring in 1-2.4%., Conclusions: The data from this report suggests that permanent prostate brachytherapy can be accomplished with minimal short- and long-term morbidity. Attention to detail as well as an appreciation to the causative factors for the morbidity will help reduce treatment-related side effects.

Purpose: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP)., Methods and Materials: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique., Results: The ABS proposes the following terminology in regard to prostate planning process: *Preplanning--Creation of a plan a few days or weeks before the implant procedure. *Intraoperative planning--Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. * Intraoperative preplanning--Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. *Interactive planning--Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. *Dynamic dose calculation--Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints., Conclusion: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.

Objective: To determine the rectal tolerance for developing Grade 2 radiation proctitis after 125I prostate implantation based on the rectal dose-volume histogram., Methods and Materials: Two hundred twelve patients with T1-T2 prostate cancer underwent 125I implantation without external beam irradiation. One month after the procedure, all patients underwent CT-based postimplant dosimetry (3-mm abutting slices). The rectal volumes, defined by an inner and outer wall, were determined from 9 mm above the seminal vesicles to 9 mm below the prostate apex. All doses were calculated by TG43 formalism. The prostate prescription dose was 160 Gy. A dose response analysis was undertaken for volumes of rectal tissue receiving a given dose. Dose levels examined were 80 Gy, 100 Gy, 120 Gy, 140 Gy, 160 Gy, 180 Gy, 200 Gy, 220 Gy, and 240 Gy. Grade 2 proctitis was defined as rectal bleeding occurring at least once a week for a minimum period of one month. The risk of proctitis was calculated using actuarial methods. For each dose level, a critical volume cutpoint was chosen to define a low and high volume group of patients. The cutpoint was determined based on two goals: minimizing thep value and finding a < or =5% risk of proctitis in the low volume group. Patients were followed from 12 to 61 months (median: 28 months) after implantation., Results: Twenty-two patients developed Grade 2 proctitis: 14% within the first year, 72% between the first and second year, and 14% during the third year after the implant date. After the third year postimplantation, no cases of proctitis were reported. Proctitis was found to be significantly volume dependent for a given dose. The prescription dose (160 Gy) delivered to < or =1.3 cc of rectal tissue resulted in a 5% rate of proctitis at 5 years vs. 18% for volumes >1.3 cc (p = 0.001). Similar results were found for all doses examined. As the rectal volume receiving the prescription dose (160 Gy) increased, so did the proctitis rate: 0% for < or =0.8 cc, 7% for >0.8-1.3 cc, 8% for >1.3-1.8 cc, 24% for >1.8-2.3 cc, and 25.5% for >2.3cc (p = 0.002)., Conclusions: Rectal dose-volume histogram analysis is a practical and predictive method of assessing the risk of developing Grade 2 proctitis after 125I prostate implantation. Delivered dose should be kept below defined rectal volume thresholds to minimize this risk. This information can allow one to decrease rectal morbidity by modifying prostate implant technique.

Purpose: We assess erectile function after prostate brachytherapy and analyze those factors affecting potency preservation., Materials and Methods: A total of 416 patients treated from October 1990 to September 1998 with permanent radioactive seed implantation for T1 to T2 prostate cancer had erectile function assessed before and after treatment. Erectile function was assessed using the scoring system of 0-complete inability to have erections, 1-able to have erections but insufficient for intercourse, 2-can have erections sufficient for intercourse but considered suboptimal and 3-has normal erectile function. Implant dose was defined as the D90, which was the dose delivered to 90% of the gland on a dose volume histogram from the 1-month computerized tomography based dosimetric analysis., Results: Pretreatment erectile function assessment revealed scores of 0 in 57 (14%), 1 in 46 (11%), 2 in 77 (18%) and 3 in 236 (57%) patients. In 313 patients who were potent with a score 2 or greater before therapy the actuarial freedom from any decrease in erectile function score was 64% and 30% at 3 and 6 years, respectively. The actuarial preservation of potency, with a score 2 or greater, was 79% and 59% at 3 and 6 years, respectively. The 2 factors found to have a significant negative effect on potency in univariate and multivariate analyses were high implant dose (D90 greater than 160 Gy. for I-125 and D90 greater than 100 Gy. for Pd-103) and a pretreatment erectile function score of 2 versus 3., Conclusions: The rate of potency preservation after brachytherapy is high, although a decrease occurs from 3 to 6 years. Pretreatment erectile dysfunction as well as higher implant dose are associated with greater impotency.

Background: Posttreatment prostate biopsy is a method of assessing local control after irradiation for prostate carcinoma. An analysis of the effect of disease- and treatment-related factors on biopsy results after prostate brachytherapy was performed to aid in patient selection and treatment optimization., Methods: Two hundred sixty-eight patients underwent posttreatment prostate biopsy (6-8 cores) 2 years after brachytherapy alone without external beam irradiation. Follow-up ranged from 24 to 111 months (median, 43 months). Implants were performed using a real-time ultrasound guided technique with the isotopes (125)I in 186 and (103)Pd in 82 patients. Ninety-eight patients underwent hormonal therapy (HT) 3 months before and 2-3 months after implant. Implant dose was defined as the D90 (dose delivered to 90% of the gland from the dose volume histogram generated using 1-month computed tomography-based dosimetry)., Results: Overall, 89% of patients (238 of 268) had negative biopsies. A positive biopsy was a predictor of biochemical failure. Patients with a positive biopsy had a 5-year freedom from biochemical failure of 40% versus 76% for patients with a negative biopsy (P = 0.0003). Univariate and multivariate analysis found that risk group, HT, and implant dose significantly affected biopsy outcome. Patients with low risk features (prostate specific antigen [PSA] 10 ng/mL or Gleason score >/= 7 or classification T2b or higher) (n = 164) (P = 0.008). Hormonal therapy was associated with a negative biopsy rate of 98% versus 84% for implant alone (P = 0.003). Patients receiving a high implant dose (D90 >/= 140 grays [Gy] for (125)I or >/= 100 Gy for (103)Pd) (n = 174) had a negative biopsy rate of 95% versus 77% for those receiving a low dose (D90 < 140 Gy for (125)I or < 100 Gy for (103)Pd) (n = 87; P < 0.001)., Conclusions: Biopsy results support the use of brachytherapy without external beam irradiation for patients with low risk features and highlight the importance of achieving an adequate implant dose., (Copyright 2000 American Cancer Society.)

Objective: An analysis of CT-based dosimetry was performed to assess the efficacy of the real time method of prostate implantation, explore the relationship of various dose descriptions and determine implant factors affecting outcome., Methods and Materials: Between 7/95 and 8/99, 297 patients underwent (125)I implants for T1-T2 prostate cancer and had CT-based dosimetry performed (TG43 formalism). Dosimetry was performed 1 month postimplant. Using a dose-volume histogram, doses delivered to 100%, 95%, 90%, and 80% of the prostate (D100, D95, D90, D80, respectively) as well as percentages of the gland receiving 240 Gy, 160 Gy, 140 Gy (V240, V160, V140, respectively) were reported. Correlations between the various dose parameters and D90 were generated. The effect of the number of seeds implanted, seeds/volume, prostate volume, experience as assessed by time (8/01/99-date of implant), ultrasound probe (mechanical sector vs. dual phased electronic), and the ratio of the CT dosimetry prostate volume/ultrasound implant volume (CT/US vol) were analyzed., Results: The median D100, D95, D90, and D80 values were 10,200 cGy, 15,655 cGy, 17,578 cGy, and 19,873 cGy, respectively. The median V240, V160, and V140 were 56%, 94%, and 98%, respectively. Correlations of dose descriptions found a close relationship of D95, D80, V240, V160, and V140 with D90 with r values of 0.928, 0.973, 0.911, 0.816, and 0.733, respectively. D100 correlated poorly with D90 (r = 0.099). Using a stepwise regression analysis, CT/US vol ratio, prostate volume, and seed number were the only significant factors affecting D90 with CT/US vol ratio having the greatest effect. The dual-phased electronic probe was associated with fewer D90 values of less than 140 Gy (2%) compared to the mechanical sector probe (14%) (p = 0.02)., Conclusion: CT-based dosimetry results reveal the real-time implant technique to be an effective method of prostate implantation. Factors associated with more precise implantation, such as decreased postimplant edema, new technology, and increased number of seeds will lead to higher D90 values.

Background: Androgen ablation may improve the efficacy of radiation therapy., Patients and Methods: A total of 296 patients who had either (125)I (206; 70%) or (103)Pd (90; 30%) transperineal prostate brachytherapy (no external-beam radiation) had routine transrectal ultrasound-guided needle biopsy (minimum six cores) 2 years after treatment without regard to disease status. Neoadjuvant hormonal therapy (NHT: leuprolide acetate and flutamide) was used in 115 patients (39%) for 3 months prior to and 3 months after the implant., Results: Of the 296 patients, 30 (10%) had positive prostate biopsies. Biopsies were positive in 4 of 115 (3.5%) v 26 of 181 (14%) of those who received or had not received NHT, respectively (P = 0.002). When patients were separated into low risk (PSA < or = 10 ng/mL, stage < or = T(2a), and Gleason score < or = 6) and high risk (all others), it was seen that low-risk patients did not benefit from NHT (3.8 v 7.7% positive biopsy rate; P = 0.5) whereas high-risk patients did (3.4% v 21.1%; P = 0.003)., Conclusion: Prostate brachytherapy yields high negative biopsy rates (90%) 2 years after treatment. Neoadjuvant hormonal therapy can improve the local control rates (as determined by biopsy) in patients undergoing (125)I or (103)Pd seed implantation. These results are most significant for patients who present with PSA >10 ng/mL, stage > or = T(2b) diseases, or Gleason score > or = 7 (high-risk status).

Purpose: Indium 111 capromab pendetide radioimmunoscintigraphy (ProstaScint) has been used to detect occult recurrent carcinoma after radical prostatectomy., Materials and Methods: We evaluated the role of ProstaScint in 24 men with rising prostate-specific antigen (PSA) level following definitive radiation therapy to differentiate between local and distant recurrence in this patient population., Results: ProstaScint scan detected prostatic uptake only in 16 patients, extraprostatic uptake in 5, both prostatic and extraprostatic uptake in 1, and no uptake in 2. Ten of 21 patients with prostatic uptake had positive biopsies, 5 had negative biopsies, and 6 were not biopsied. Two of the three patients with negative scans had positive biopsies, and the third patient was not biopsied. Three patients had evidence of osseous metastasis on radionuclide bone scan, two corresponding to the sites detected on ProstaScint. All three patients had abnormal uptake beyond the prostatic fossa with (n =2) or without (n = 1) prostatic uptake. There were no positive bone scans in patients without extraprostatic uptake on ProstaScint., Conclusions: ProstaScint scan is useful in detecting occult recurrence outside the prostate in patients with rising PSA following radiation therapy. Compared to data from radical prostatectomy, ProstaScint scans in these patients reveal a higher prevalence of abnormal uptake in the prostate and less frequent extraprostatic uptake.

Purpose: Patients with localized prostate cancer who had a prior open prostatectomy or transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) may be at risk for greater morbidity when treated with brachytherapy. This analysis examines the morbidity following brachytherapy using the real-time method to determine if patients with a history of TURP are at increase risk for developing complications., Materials and Methods: An ultrasound-guided transperineal interactive prostate seed was implanted in 419 patients with T1-T2 prostate cancer. All patients were implanted using a peripheral weighting of sources (75%) with the interior sources placed at least 5 mm from the urethra. The patients were divided into two groups: group 1 consisted of 376 patients (89.7%) without a prior TURP, and group 2 consisted of 43 patients (10.3%) who had a TURP prior to their implant. The mean age, prostate-specific antigen level, Gleason score, clinical stage, prostate volume, isotope implanted, and number of patients treated with neoadjuvant hormone therapy were comparable for both groups., Results: Median follow-up for group 1 was 12 months and for group 2 was 18 months. No patients suffered from radiation-related proctitis or cystitis in either group of patients. Two patients in group 2 implanted with iodine 125 and who had a history of two prior TURPs developed mild superficial urethral necrosis (SUN). The actuarial freedom from developing superficial urethral necrosis at 4 years was 84% in patients with a history of prior TURP. There were no episodes of SUN in group 1 and no cases of incontinence reported in either group of patients. The actuarial rate of potency was 78% at 2 years., Conclusion: Whereas other techniques of seed implantation report incontinence in patients who had a prior open prostatectomy or TURP, the real-time method combined with peripheral loading avoids this complication.

Purpose: This review describes two studies to evaluate artificial neural networks (ANNs) in prostate cancer staging. In the first study, an ANN was trained to identify prostate cancer patients at low risk of lymph node spread (LNS). The second study evaluated an ANN to predict capsular penetration (CP) in men with clinically localized prostate cancer. An accurate assessment of lymph node status will help identify those brachytherapy patients in whom lymphadenectomy can be avoided. The accurate prediction of CP can help determine the appropriateness of brachytherapy as a treatment option., Materials and Methods: An ANN to predict LNS was trained and tested using a database from one institution (n = 4,133) and validated using two databases (n = 330 and n = 227) from different institutions. The clinical variables used were clinical stage (cTNM), Gleason sum, and prostate-specific antigen concentration (PSA). The ANN to predict CP was trained and validated with data from a single institution (n = 409). The variables used were age, race, PSA, PSA velocity, Gleason sum, and cTNM., Results: The LNS ANN was able classify 76%, 75%, and 30% of the patients in each database as being at low risk of LNS with 98% accuracy. The CP ANN correctly identified CP in 25 (84%) of patients and produced 5 (16%) false-negative predictions., Conclusions: These preliminary results suggest that ANNs can be useful in staging prostate cancer. If sufficiently accurate ANNs can be developed and tested, they have the potential to increase the accuracy of clinical staging and thus improve treatment decisions.

Purpose: To describe a method of creating an intraoperative dosimetric representation of the real-time ultrasound-guided prostate implant., Materials and Methods: An intraoperative dosimetry system (Multi Media Systems [MMS]) captures transverse ultrasound images after peripheral needles have been implanted in the prostate. The prostate contour and needle positions are outlined on the system. The volume of the prostate with needles in place is calculated. As seeds are deposited in the actual implant, the positions of the seeds are marked on the intraoperative system. Following implantation of the peripheral needles, the resulting isodose lines are displayed. The interior needles are inserted into the prostate, and these positions are captured on the system. As seeds are deposited through these needles into the prostate, their positions are captured on the planning system. When the implant is complete, the final dose coverage and dose volume histogram can be visualized., Results: Ten consecutive patients underwent iodine 125 implants using real-time intraoperative isodose generation. The ratio of the preneedle prostate volume to postneedle prostate volume ranged from 0.89 to 1.0 (median 0.97). The calculated dose delivered to 90% of the prostate volume from the dose volume histogram (D90) ranged from 146.5 to 194 Gy (median 174.75 Gy). The percentage of the prostate covered by 240 Gy ranged from 14.6% to 59% (median 40.75%)., Conclusion: Dosimetric representation of the real-time ultrasound-guided prostate implant can be achieved and demonstrates the efficacy of this brachytherapy technique.

Purpose: To determine if dynamic cystography can replace cystoscopy following prostate seed implantation., Materials and Methods: Three hundred three consecutive patients underwent prostate seed implantation using the real-time method. Following implantation, 60 cc of contrast media was injected into the bladder using continuous fluoroscopy. If any seed motion was detected, cystoscopy was performed and any seeds encountered were removed. Patients were followed after discharge for any seeds passed in the urine., Results: Of the 303 patients, 3 (1%) were found to have one or more seeds in the bladder. No patients passed seeds following discharge. There were no adverse events associated with the cystography., Conclusion: Dynamic cystography can replace cystoscopy as the postimplant study to evaluated misplaced intravesical or urethral seeds.

Purpose: To analyze the results of ultrasound-guided brachytherapy for stage T1-T2 prostate cancer, as shown by biopsy results., Patients and Methods: The 268 patients (mean age 66 years; range 41-83 years) underwent real-time ultrasound-guided implantation of either iodine-125 (N = 186) or palladium-103 (N = 82) seeds. Of these patients, 96 (36%) received total androgen suppression for 3 months prior to and 3 months after implantation. Prostate biopsy was performed 24 months later, with the six to eight cores all being interpreted by the same pathologist. Each specimen was rated either positive or negative for cancer., Results: Of the 268 patients, 238 (89%) had a negative biopsy at 24 months. Among the patients receiving androgen suppression, 2% were found to have positive biopsies compared with 16% of those not given hormones (P = 0.004). Of the 155 patients with stage T1-T(2a) cancer, 6% had a positive biopsy compared with 19% of patients with stage T(2b) or T(2c) cancer (P = 0.001). In the entire series, the pretreatment serum concentration of prostate specific antigen, Gleason score, and isotope (I v Pd) were not significant predictors of a positive biopsy. However, among the 172 patients who did not receive androgen suppression, all three factors were predictive: 42% for Gleason score of 7 to 10 v 13% for Gleason score < or =6 (P = 0.001): 25% for pretreatment PSA concentration >10 ng/mL v 13% for PSA < or = 10 ng/mL (P = 0.05); and 27% for stage T(2b) or T(2c) v 9% for stage T1 or T(2a) (P = 0.001). The isotope used and the last PSA value were not significant predictors., Conclusion: Brachytherapy provides excellent local control of prostate cancer, with 89% of patients having negative biopsies 2 years after treatment. High-risk patients may benefit from the addition of androgen suppression.

Objectives: Permanent implantation with (125)I in patients with localized prostate cancer who have prostate volumes >/= 50 cm(3) is often technically difficult owing to pubic arch interference. The objective of this study was to describe dosimetry outcomes in a group of patients who were implanted using the real-time ultrasound-guided technique who had prostate volumes >/= 50 cm(3)., Materials and Methods: A total of 331 patients received an (125)I prostate seed implant from January 1, 1995, to June 1, 1999, of whom 66 (20%) had prostate volumes >/= 50 cm(3) at the time of the procedure. The real-time seed implant method was used in all patients and consisted of intraoperative planning and real-time seed placement using a combination of axial and sagittal ultrasound imaging. Pubic arch interference was managed using an extended lithotomy position or by angling the tip of the ultrasound probe in an anterior direction. No preimplant pubic arch CT scan study was performed and no patients were excluded from treatment because of prostate size. Implant quality was assessed using CT-based dosimetry performed 1 month postimplant. Dose-volume histograms for the prostate, bladder, rectum, and urethra volumes were generated. The target dose for these implants was 160 Gy and an adequate implant was defined as the dose delivered to 90% of the prostate (D90) >/= 140 Gy. The dose delivered to 95% of the prostate (D95) and doses to 30% of the rectal (DRECT30) and urethral (DURE30) volumes were also calculated., Results: Prostate volumes in the 66 patients ranged from 50 to 93 cm(3) (median 57, mean 61 cm(3)). Total activity implanted was 27.8-89.1 mCi (median 57 mCi), with a range in activity per seed of 0.36-0.56 mCi (median 0.4 mCi). The prostate D90s and D95s ranged from 13,245 to 22,637 cGy (median 18,750) and 11,856 to 20,853 cGy (median 16,725), respectively. Only one patient (1.5%) had a D90 < 140 Gy. The DURE30 values ranged from 15,014 to 27,800 cGy (median 20,410) and the DRECT30 values were 3137-9910 cGy (median 5515)., Conclusion: Implantation of the large prostate can be accomplished using the real-time method. A total of 98.5% of the patients receive a high-quality implant. In addition, these implants should not put patients at increased risk for significant urinary and bowel complications because urethral and rectal doses can be kept at acceptable levels.

Purpose: Combined brachytherapy of the prostate and external beam irradiation (EBRT) of the prostate and seminal vesicles (SV) is becoming a popular treatment for high-risk prostate cancer. Dose-volume histogram (DVH) analysis of the SV in patients undergoing this treatment was performed to determine the dose distribution to the SV and the adequacy of this treatment in patients with potential SV involvement., Methods and Materials: Twenty-five consecutive patients were treated with a Pd-103 implant of the prostate alone and 45 Gy of EBRT to the prostate and SV. Attempts were not made to implant the SV but seeds were routinely placed at the junction of the prostate and SV. All patients underwent CT-based postimplant dosimetric analysis 1 month after implantation. As part of this analysis, DVH were generated for the prostate and total SV volume (SVT). In addition, the SV was divided into 6-mm-thick volumes identified as SV1, SV2, SV3, SV4, and SV5 starting from the junction of the prostate and SV and extending distally. DVH were also generated for these structures. Delivered dose was defined as the D90 (dose delivered to 90% of the organ on DVH)., Results: The median volumes in cc of the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 34.33, 9.75, 2.7, 3.48, 2.92, 3.18, and 1.96 respectively. The SVT contained from 0-9 seeds (median 2). There was little dose delivered to the SVT and SV volumes from the implanted prostate. The median D90 values for the prostate, SVT, SV1, SV2, SV3, SV4, and SV5 were 8615 cGy, 675 cGy, 3100 cGy, 1329 cGy, 553 cGy, 246 cGy, and 67 cGy, respectively. The dose delivered to the prostate covered small percentages of SV. The percents of SV volumes covered by the prostate D90 were 11, 35, 3.3, 0, 0, and 0 for SVT, SV1, SV2, SV3, SV4, and SV5, respectively., Conclusions: DVH analysis of the SV reveals that dose generated from an implanted prostate contributes little to the SV. Those patients at high risk for SV involvement may be undertreated with combined EBRT to prophylactic doses and prostate implantation.

Purpose: Patients who present with localized and locally advanced prostate cancer may be candidates for prostate brachytherapy. We evaluated the treatment outcomes in a diverse group of prostate cancer patients who presented with low, moderate and high risk features., Materials and Methods: A total of 301 patients who presented with T1 to T3 prostate cancer were treated with brachytherapy alone or combined with hormonal therapy and/or external beam irradiation. Of these patients 109 at low risk with prostate specific antigen (PSA) 10 ng./ml. or less, Gleason score 6 or less and clinical stage T2a or less were treated with 125iodine alone, 152 at moderate risk with PSA greater than 10 ng./ml., Gleason score greater than 6 or stage T2b or greater were treated with 125iodine or 103palladium or combined implant alone with 5 months of hormonal therapy, and 40 at high risk with PSA greater than 15 ng./ml., Gleason 8 or greater, clinical stage T2c to T3 or positive seminal vesicle biopsy (20) were treated with combination brachytherapy, external beam irradiation and 9 months of hormonal therapy. Patients with a positive seminal vesicle biopsy (T3c disease) and negative pelvic lymph nodes were included in the high risk group, and the walls of the seminal vesicles were also treated with implantation. Followup was performed every 6 months with digital rectal examination and ultrasound evaluation. Prostate biopsy was routinely recommended 2 years after completion of the radiation. Failure was defined as PSA increase on 2 consecutive determinations above 1 ng./ml. or evidence of local recurrence on digital rectal examination, transrectal ultrasound or biopsy. Kaplan-Meier projections were used to calculate progression-free survival rates., Results: Of the 109 patients at low risk followed from 1 to 7 years (median 18 months) 91% were free of PSA failure at 4 years. No patient experienced urinary incontinence following implantation, although grade 1 to 2 radiation proctitis occurred in 5 (4.5%). Of the 152 patients at moderate risk 73 received implantation and 79 received implantation combined with hormonal therapy. The 4-year biochemical freedom from failure rate for the hormone group was 85% versus 58% for the no hormone group (p = 0.08). The difference was more significant for those with Gleason score 7 or greater (90 versus 43%, p = 0.01) and for those with PSA greater than 10 ng./ml. (87 versus 59%, p = 0.04). Grade 1 to 2 radiation proctitis occurred in 1 of the 79 patients (1.3%) receiving hormonal therapy and in 3 (4%) treated with implantation only. There were no cases of urinary incontinence. Of the 40 patients at high risk 71% were free of biochemical failure at 3 years. Of the 4 patients with failure (10%) 3 (75%) originally had positive seminal vesicle biopsies. Five patients experienced gastrointestinal complications, although none was grade 3 or 4. The actuarial freedom from grade 2 proctitis was 82%. No patient experienced urinary incontinence. Prostate biopsies were negative in 87% of the low risk, 96.8 (hormone group) versus 68.6% (no hormone group) of the moderate risk (p = 0.0023) and 86% of the high risk patients., Conclusions: Brachytherapy appears to offer comparable results to external beam irradiation and radical prostatectomy when patients are stratified by disease extent. Adopting a strategy of implant alone, implant with hormonal therapy or implant with hormonal therapy and external beam irradiation in patients who present with low to high risk features can improve the overall results in the more advanced cases.

Prostate brachytherapy has come a long way in the last 15 years, from an open free-hand technique with which seed placement was often inaccurate to the highly technical and accurate procedure of today. It has become a viable treatment option for low-risk patients along with EBRT and prostatectomy. Its most promising use may be in combination with hormonal therapy and EBRT in moderate- to high-risk patients, for whom it may offer improved outcomes over standard single-modality therapies.

Although there is renewed interest in prostate brachytherapy, little information is available on the effect of the procedure on prostate-specific antigen (PSA) changes over time. This study describes PSA kinetics after iodine-125 (I-125) transrectal ultrasound-guided transperineal implantation of the prostate. From February 1991-September 1997, 207 patients were treated with an I-125 prostate implant alone for T1-T2 prostate cancer. PSA values were obtained prior to treatment and at 1-73 months (median, 24 months). The change in PSA after implantation of the prostate was measured as a fraction of the pretreatment PSA (PSA at follow-up/pretreatment PSA). PSA failure was defined as two elevations in PSA or PSA > 1 ng/ml. One hundred fifty-five patients had PSA values recorded at the 1-month time period. A PSA value greater than the pretreatment PSA at 1 month was found in 27% (42/155). This had no significant effect on future PSA failure. The median percentage change in PSA after implantation for all patients were as follows: 1 month, 0.73; 3 months, 0.30; 6 months, 0.18; 12 months, 0.12; 18 months, 0.12; 24 months, 0.08; 30 months, 0.07; 36 months, 0.08; 42 months, 0.08; and 48 months, 0.05. The most significant decline occurred in the first 12 months. This was followed by a more gradual decline between 12-24 months. There was little change in PSA values after 24 months. The 1-year PSA value had a significant effect on PSA failure. Patients with a 1-year PSA <1 ng/ml (66) had an actuarial 4-year freedom-from-failure rate of 90%, compared to a rate of 62% for those with values >1 ng/ml (69) (P = 0.002). Twenty-seven patients developed PSA failure. The time to PSA failure ranged from 12-48 months (median, 24 months), but most (20/27) failures occurred after 18 months. We conclude that the greatest decline in PSA after I-125 implantation of the prostate occurs during the first year, and little change occurs after 2 years. A 1-year PSA value > 1 ng/ml is highly predictive of eventual PSA failure, which occurs in most patients after 18 months posttreatment.

Purpose: Urinary retention is a frequently reported complication following radioactive seed implantation of the prostate. If retention is refractory, a post-implant transurethral prostatic resection may ultimately be required to relieve obstruction, leading to an increased risk of urinary incontinence. In this series the incidence of prolonged urinary retention was determined, and the effect of pretreatment and treatment related factors was analyzed to identify high risk patients., Materials and Methods: A total of 251 patients with organ confined prostate carcinoma underwent transperineal prostate seed implantation. Of the patients 114 were implanted with 103palladium (103Pd) and 137 with 125iodine seeds. Of the patients who were implanted with 103Pd 90 received 3 months of neoadjuvant hormonal therapy. All patients had International Prostate Symptom Scores (I-PSS) recorded before implantation to assess the degree of urinary symptoms. In the patients receiving neoadjuvant hormones prostate volumes and I-PSS were recorded before initiation of hormone treatment and 3 months later at the time of implant., Results: Urinary retention developed in 14 patients requiring catheterization for more than 48 hours. Median time to onset was 1 day after implant. Of these patients 6 ultimately required transurethral prostatic resection to relieve urinary obstruction. No patient had urinary incontinence following implantation or transurethral prostatic resection. Multivariate analysis revealed that pretreatment I-PSS, and combined treatment with hormonal therapy and 103Pd predicted for the development of retention. Patients with I-PSS 20 or greater had a 29% risk, I-PSS 10 to 19, 11% risk and I-PSS less than 10, 2% risk of retention. Neither patient age, clinical stage, prostate specific antigen, Gleason score, use of 125I nor prostate volume was significant. A subgroup analysis of patients receiving hormonal therapy and 103Pd revealed that those with persistent urinary symptoms (I-PSS 10 or greater) following 3 months of hormonal therapy had the greatest risk of prolonged retention (37%)., Conclusions: The overall risk of prolonged urinary retention following prostate implantation was low in our series. Using the I-PSS questionnaire, high risk patients can be identified before treatment. Patients with significant pretreatment urinary symptoms or persistent urinary symptoms following 3 months of hormonal therapy and then implantation with 103Pd have the greatest risk.

Purpose: No dose-response study has ever been performed for I-125 prostate implants using modern techniques of implant evaluation and modern treatment outcome end points. The amount of activity per volume implanted was increased over time based on review of postimplant dosimetry. This resulted in different delivered dose levels. This study explores the relationship between dose, biochemical failure, and biopsy results., Materials and Methods: 134 patients with T1-T2 prostate cancer were implanted with I-125 radioactive seeds and followed from 12 to 74 months (median: 32) postimplant. No patient received external beam irradiation or hormonal therapy. All patients implanted with I-125 had Gleason scores < or =6. One month postimplant, a CT-based three-dimensional dosimetric evaluation was performed on all patients. Using TG43 guidelines, dose-volume histograms were calculated. The dose delivered to the gland was defined as the D90 (dose delivered to 90% of prostate tissue as defined by CT). The D90s ranged from 26.8 to 256.3 Gy (median: 140.8 Gy). Biochemical failure was defined as two consecutive rises in prostate specific antigen (PSA) or a nadir level above 1.0 ng/ml. Posttreatment prostate biopsies (six to eight core samples) were routinely performed at 2 years postimplant., Results: Improvements in freedom from biochemical failure (FFBF) rates were seen with increasing D90 levels. The 4-year FFBF rates for patients with D90 values < 100 Gy, 100-119.9 Gy, 120-13.9 Gy, 140-159.9 Gy, and > or =160 Gy were 53, 82, 80, 95, and 89%, respectively (p = 0.02). Patients receiving a D90 < 140 Gy (65 patients) were similar with respect to presenting disease prognostic factors to those receiving a D90 > or =140 Gy (69 patients). Patients receiving a D90 < 140 Gy had a 4-year FFBF rate of 68% compared to a rate of 92% for those receiving a D90 > or =140 Gy (p = 0.02). Two-year posttreatment biopsies were negative in 70% (33 of 47) of patients with a D90 < 140 Gy compared to a rate of 83% (24 of 29) in patients with a D90 > or =140 Gy (p = 0.2). A multivariate analysis using dose, PSA, score, and stage revealed that dose was the most significant predictor of biochemical failure (p = 0.001). This dose response was more pronounced in patients presenting with PSA levels > 10 ng/ml. In these patients, the 4-year FFBF rates were 51 and 100% for the low and high dose groups, respectively (p = 0.009) and the negative biopsy rates were 64% (14 of 22) and 100% (8 of 8), respectively (p = 0.05). In patients with presenting PSA <10 ng/ml, the 4-year FFBF rates were 82 and 88% for the low and high dose groups, respectively (p = 0.29)., Conclusion: A dose response was observed at a level of 140 Gy. Adequate I-125 implants should deliver a dose of 140-160 Gy using TG43 guidelines.

The objective of this paper was to evaluate the acute urinary morbidity associated with I-125 interstitial implantation of the prostate gland. From 1991-1995, 117 patients underwent ultrasound (U/S)-guided implantation of the prostate gland. Median dose to 90% of the gland (d90) was 14.68 Gy (range = 1.65-21.75 Gy). The patients' urinary symptoms were recorded pre-implantation and at regular intervals after implantation using the International Prostate Symptom Score (IPSS), a self-assessment questionnaire in which patients scored 7 symptoms: incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Median follow-up was 12 months. The natural history of implant-related urinary symptoms was assessed in this manner. In addition, dosimetric factors including U/S prostate volume, total activity, activity per seed, dose volume histogram (DVH) values for dose to gland, and dose area histogram (DAH) values for dose to urethra and bladder were examined for correlation to the severity of each symptom as well as to total IPSS (sum of the individual symptom scores). Total IPSS peaked at 1 month post-implant and gradually returned to approximately baseline at 24 months. Total IPSS directly correlated with total activity and DVH for the prostate. Total IPSS, however, did not correlate with bladder or urethral DAH. With the exception of frequency, individual symptoms did not correlate with dose to gland, bladder, or urethra. Frequency scores did, however, correlate not only with dose to prostate gland but also dose to urethra. The acute urinary side effects of I-125 prostate implantation are transient and peak at 1 month post-implant. The severity of the urinary irritative symptoms developed are closely related to total dose to the gland. Urethral dose appears to affect frequency most significantly. Urinary symptoms, therefore, may be a limiting factor when considering dose escalation with I-125.

The objectives of this study were to examine the effect of both disease and treatment related prognostic factors on biochemical control and post-treatment biopsy. Two-hundred fifty-eight patients underwent interactive ultrasound guided transperineal prostate implantation for T1-T2 prostate cancer using Iodine-125 (139 patients) and Palladium-103 (119 patients) and were followed from 6-67 months (median, 19). Hormonal therapy with 3 months of leuprolide and flutamide prior to implantation and two months given after the implant was used in 96 patients. Pre-treatment prostate-specific antigen (PSA) had the most significant effect on biochemical failure. Freedom from biochemical failure (FFBF) rates at 4 years were 75% for patients with PSA 1.3-10 ng/ml (144), 74% for patients with PSA 10.1-20 ng/ml (73), and 34% for patients with PSA > 20 ng/ml (41) (P = 0.0004). Gleason score also had a significant effect on FFBF rates. Four-year rates were 81%, 65% and 47% for patients with scores of 2-4 (68), 5-6 (130), and > or = 7 respectively (60) (P = 0.01). These two factors were also significant in multivariate analysis (P = 0.002, 0.007, respectively). Gleason score was the only factor to significantly affect post-treatment biopsy results. Patients with scores of 2-6 had 85% (63/ 74) negative 2-year biopsies versus 62% (13/21) for patients with scores > or = 7 (P = 0.02). Low-risk patients (PSA < or = 10 ng/ml, scores < 7 and stage < T2a) had a 4-year FFBF rate of 88% as compared to 60% for high-risk patients (PSA > 10 ng/ml, score > 6 or stage > or = T2b) (P = 0.02) and had a 95% negative biopsy rate versus 76% for high-risk patients (P = 0.06). Low-risk patients demonstrate high FFBF and negative biopsy rates following implantation. Patients presenting with higher risk prognostic factors such as PSA > 20 ng/ml or Gleason scores > or = 7 may require more aggressive treatment regimens.

Purpose: Interstitial brachytherapy plays an important role in the treatment of advanced and recurrent gynecologic malignancies. Unfortunately, the inability to visualize the tumor and surrounding normal structures during the implant has hampered the accuracy and safety of the implant. Transrectal ultrasound guided Syed-Neblett template implantation is a new technique for performing interstitial implants under direct visualization. The details of the technique are presented to demonstrate the ability to accurately guide needle placement into tumor and avoid needle insertion into critical surrounding normal structures., Methods and Materials: The transrectal ultrasound is positioned so that it can visualize the tumor, and normal surrounding structures in both transverse and longitudinal planes. The Syed-Neblett template is positioned and sutured into the perineum. Needles are inserted into the target area under direct visualization through transverse imaging. The bladder and rectum can be directly imaged and thus avoided. Longitudinal imaging is then used to guide the needles to the appropriate depth. In addition, it can be used to assess the length of the target volume and aid in determining the active length of the sources., Results: A total of 12 procedures have been performed on seven patients from August 30, 1995 to April 12, 1996. The presenting diseases included: Stage IIIb cervical cancer in four cases, recurrent endometrial cancer in two cases, and Stage III vaginal cancer in one case. The total length of time for implantation of the needles ranged from 45 to 165 min (median--130 min)., Conclusion: Transrectal ultrasound guidance provides real-time visualization of the target volume and normal tissues during interstitial implantation of gynecologic malignancies and allows for accurate needle placement.

Background: Interactive, transrectal, ultrasound-guided transperineal implantation is a new technique for performing permanent brachytherapy implants of the prostate. Prostate specific antigen (PSA) findings, biopsy results, and morbidity are examined to demonstrate its efficacy and safety in treating early stage prostate carcinoma., Methods: Ninety-seven patients underwent permanent implants for classifications T1 to T2 adenocarcinoma of the prostate gland with a median follow-up of 18 months (range: 6-51 months). Seventy-nine patients had negative laparoscopic pelvic lymph node dissections prior to implantation. Patients with positive lymph nodes were not implanted. The radioactive isotope used was I-125 in 71 patients and Pd-103 in 26 patients., Results: PSA failure was defined as two consecutive increases in PSA above the nadir level. The actuarial freedom from PSA failure (FFPF) at 2 years was 76% for the entire group. Stage significantly affected FFPF. Patients classified as T1b to T2a (35) had a FFPF of 91% at 2 years compared with 68.5% for patients classified as T2b to T2c (62) (P = 0.04). The pre-treatment PSA also significantly affected FFPF. Patients with PSA values of < or = 10 ng/mL (44) had a FFPF of 83% at 2 years. A similar rate of 82% was found in patients with PSA values of 10.1 to 20 ng/mL (29). Patients with PSA values > 20 ng/mL (24) had a significantly poorer FFPF at 2 years of 58% (P = 0.02). The PSA values of patients free from a PSA failure (82) ranged from 0.1 to 12.9 ng/mL with a median of 0.8 ng/mL. Transrectal prostate biopsies were performed 18 to 36 months posttreatment in 39 patients. Negative biopsies were found in 74% (29/39) of cases. The procedure was associated with an actuarial preservation of erectile function rate and sexual potency at 2 years of 96% and 79%, respectively. There were no cases of urinary incontinence or radiation cystitis. Associated morbidity included urinary retention requiring catheterization in 4% of the patients, outlet obstruction requiring a transurethral resection of the prostate in 2% and Grade 2 rectal complications in 1%., Conclusions: Interactive, ultrasound-guided transperineal brachytherapy results in a low PSA failure rate, high negative biopsy rate, and is associated with low morbidity and preservation of erectile function.

Objective: The purpose of this paper is to describe the CT findings in patients undergoing transperineal sonographically guided radioactive seed implantation with and without laparoscopic lymph node dissection for treatment of carcinoma of the prostate gland., Materials and Methods: Ninety-six CT scans of the pelvis were retrospectively reviewed in patients who had undergone radioactive seed implantation of the prostate gland. The CT readings were correlated with the type of procedure each patient had and the pathologic results of laparoscopic lymph node dissection., Results: Of 73 patients who underwent laparoscopic lymph node dissection, 42 were found at CT to have low-attenuation masses along lymph node chains. These masses resembled necrotic nodes. Only one patient who did not undergo laparoscopic lymph node dissection had similar findings. Fourteen patients had fluid collections within the pelvis, 13 of whom had undergone laparoscopic lymph node dissection. Other imaging findings included ectopic seeds (10 patients) and subcutaneous and intrapelvic air (11 patients). All except two patients had negative pathology reports for the removed lymph nodes., Conclusion: A wide variety of imaging findings may be seen after radioactive seed implantation and laparoscopic lymph node dissection, including masses that resemble necrotic lymph nodes. Radiologists should be aware of these findings in asymptomatic patients.

Purpose: The effect of a therapeutic modality on sexual potency is often an important consideration for patients choosing a treatment for prostate cancer. We prospectively assessed patients' penile erectile function before and following interactive ultrasound-guided transperineal permanent radioactive seed implantation to determine its effect on sexual function., Methods and Materials: Eighty-nine patients underwent permanent radioactive seed implantation from June 1990 to April 1994 for localized prostate cancer (T1-T2) and were followed for a median of 15 months (1.5-52 months). 125I seeds were implanted in 73 patients with a combined Gleason grade of 2-6, and 103Pd seeds were implanted in 16 patients with higher grade lesions. The sexual potency of these patients was assessed prior to, at 3 and 6 months, and every 6 months after implantation. Erectile function was graded using a numerical score of 0 to 3 (0 = impotent (no erections), 1 = ability to have erections but insufficient for vaginal penetration, 2 = erectile function sufficient for vaginal penetration but suboptimal, 3 = normal erectile function). The pretreatment potency scores were as follows: 0 in 24 patients, 1 in 6 patients, 2 in 22 patients, and 3 in 37 patients., Results: The actuarial impotency rates (score = 0) following implantation for those patients possessing some degree of erectile function prior to implantation (65 patients) were 2.5% at 1 year and 6% at 2 years. The actuarial decrease in sexual function rates (a drop in score of at least one point) were 29% at 1 year and 39% at 2 years. Only two patients became impotent following treatment and this occurred at 1 year and 16 months. The time period for a decrease in erectile function to occur ranged from 1.8 months to 32.7 months, with a median of 6.8 months. Patients with higher grade tumors showed a greater decrease in potency score compared to patients with lower grade tumors., Conclusion: Interactive ultrasound-guided transperineal brachytherapy for the treatment of localized prostate cancer is associated with preservation of erectile function in the vast majority of patients, although a minor decrease in potency is not uncommon.

A total of 71 men with clinical T1b-T2c carcinoma of the prostate underwent ultrasound-guided interactive seed implantation of the prostate. Sixty received 125I and II 103Pd implants. A laparoscopic lymph node dissection was performed in 58 patients. The patients have been followed a mean of 2 years (1-4.2 years). With use of a prostate specific antigen (PSA) value of 1 ng/ml, patients (n = 8) who presented with an initial PSA of < or = 4.0 ng/ml were all free from failure. This compared with those who presented with an initial PSA of 4.1-10, 10.1-20, and > or = 20 ng/ml, in whom the freedom from failure rates were 52, 32, and 22%, respectively. Patients (n = 49) who presented with an initial PSA of less than or equal to 15 ng/ml had a median PSA of 0.88 ng/ml at last follow-up compared with 2.25 ng/ml for those with an initial PSA of > 15 ng/ml. Prostate biopsies performed 18-24 months after implantation were negative in 82%. The median PSA for those with a negative biopsy was 0.7 ng/ml vs. 4.9 ng/ml for those with a positive biopsy. There were no long-term persistent urinary complaints. Grade 2 radiation proctitis occurred in three (4.2%). No cases of severe radiation proctitis or cystitis occurred. Urinary retention occurred in four patients (5.6%), one of whom required a transurethral resection of the prostate. No patients developed urinary incontinence. Potency was preserved in 94%. We conclude that the real-time ultrasound-guided transperineal seed implantation technique is an effective and safe method of treating prostate cancer. Longer follow-up is needed to substantiate these early encouraging results.

Laparoscopic pelvic lymph node dissection with real-time interactive transrectal ultrasound guided transperineal radioactive seed implantation is a new method of treatment for localized carcinoma of the prostate. A total of 58 patients with clinically confined prostate cancer and negative seminal vesicle biopsies underwent staging laparoscopic pelvic lymph node dissection immediately followed by prostate implantation: 50 had 125iodine and 8 had 103palladium implants. Mean operating time was 226 minutes (range 120 to 475), mean blood loss was 57 cc (range 5 to 400) and average hospital stay was 2.2 days (range 0.5 to 8). At a mean followup of 12 months (range 6 to 24), complications included proctitis in 1.7% of the cases, dysuria in 24%, nocturia in 21% and outlet obstruction in 17%. Erectile function remained unchanged. Prostate volume decreased to 58.9% of the pretreatment value by 12 months and to 44.3% by 24 months. Mean prostate specific antigen level was 18.4 +/- 26.3 ng./ml. before treatment, 3.4 +/- 3.9 ng./ml. at 6 months, 2.3 +/- 2.3 ng./ml. at 12 months and 4.9 +/- 6.0 ng./ml. at 24 months (1.2 +/- 1.0 ng./ml. for patients with no evidence of disease). Of the patients 15.8% had local failure at 18 to 24 months as determined by positive transrectal ultrasound guided biopsy. Five of 58 patients (8.6%) had persistently elevated prostate specific antigen levels, only 1 of whom had a positive biopsy. Laparoscopic pelvic lymph node dissection with transrectal ultrasound guided implantation is a safe and promising mode of therapy for patients with localized prostate cancer.

Purpose: Ultrasound-guided transperineal prostate implantation is a new technique for performing permanent isotope implants of the prostate. The details of the technique are presented to demonstrate its ability to place radioactive seeds three-dimensionally within the prostate gland to achieve uniform dose distribution without the need for complicated preplanning., Methods and Materials: An accurate measurement of the prostate volume is made using biplanar transrectal ultrasound. The total activity to be implanted is derived from a look-up table based on prostate volume. The basic plan is to implant 60-70% of the total activity in the periphery of the gland and the remaining activity in the interior of the gland. The ultrasound transducer provides visualization of the prostate through transverse, longitudinal and oblique cuts and allows for accurate placement of implant needles, approximately 1 cm apart. In addition, these needles can be moved through the prostate under constant visualization, thus allowing for precise seed placement., Results: The setup of the transrectal ultrasound device as well as prostate volume measurements are performed in 10 to 15 min. The actual placement of the needles and seed implantation takes 1 to 1.5 h to perform. Postimplantation dosimetric evaluation is performed using orthogonal x-ray films and 3 mm thick CT slices taken at 3 mm intervals. This evaluation has confirmed accurate seed placement within the prostate gland., Conclusion: Interactive ultrasound guided transperineal prostate implantation is a fast and accurate method of performing permanent radioactive isotope prostate implants.

Abstract Background Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required. Methods/Design This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (125I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with 125I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during 125I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB. The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events. Discussion To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa. Trial registration UMIN000003992