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Background: Salvage brachytherapy is a treatment option for patients with locally recurrent prostate cancer after primary radiation therapy. We reviewed our experience using low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy to compare the outcome and toxicity profiles of each approach in the salvage brachytherapy setting., Methods and Materials: Ninety-eight patients with biopsy-proven locally recurrent prostate cancer who underwent salvage brachytherapy (LDR = 37; HDR = 61) following an initial course of definitive radiotherapy between 4/2003 and 4/2015 were retrospectively reviewed. All patients underwent salvage brachytherapy using LDR or HDR. Androgen deprivation therapy was used in 45% of the patients. Prostate-specific antigen (PSA) failure was determined using the Phoenix (nadir+2) definition. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4 and patient-reported questionnaires., Results: Median followup was 31 months. The 3-year PSA relapse-free survival (RFS) was 60.1% (95% CI, 49.6-72.5%). There was no difference between LDR and HDR brachytherapy in terms of PSA RFS (p = 0.84 by log-rank test). On multivariate analysis, only prostate-specific antigen doubling time (PSADT) <12 months was significantly associated with PSA relapse. The 3-year PSA RFS for patients with a PSADT <12 months was 39% compared with 73% for PSADT ≥12 months (p = 0.002 by long-rank test). There were no statistically significant differences in toxicity between LDR and HDR brachytherapy. There was a higher peak in urinary symptoms in LDR patients; however by 24-36 months, most patients in both groups returned to baseline., Conclusions: Both LDR and HDR salvage brachytherapy are an excellent treatment options for appropriately selected patients with comparable outcome and toxicity. Patients with a PSADT < 12 months seem to have worse outcomes., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: To evaluate the incidence and predictors of hip toxicity postradiotherapy for localized prostate cancer., Methods and Materials: 4067 prostate cancer patients were treated with external beam radiotherapy (EBRT; n=2569; 63%) or brachytherapy with or without supplemental EBRT (n=1508; 27%). 43% (n=1738) were treated with neo-adjuvant and concurrent ADT and 57% (n=2329) with radiotherapy alone. Hip toxicity was defined as moderate or severe pain upon ambulation with or without the need for hip-revision surgery. Median follow-up was 7years (range, 3-21years)., Results: One hundred twenty-one (2.7%) patients developed moderate-to-severe hip pain after radiotherapy affecting ambulation. Of these, 73 (60%) required hip replacement secondary to persistent hip pain. Among patients with baseline degenerative joint disease (DJD) changes on scans, 10-year incidence of hip-related toxicity was 11% versus 3% for those without such changes (P<.001). The only variables on multivariate analysis associated with hip-related toxicity post-radiotherapy were baseline DJD on imaging (P<.0001) and prolonged ADT for salvage therapy (P<.0001)., Conclusions: Prostate EBRT or brachytherapy is associated with low incidence of long-term hip-related toxicity. The only variables identified associated with hip toxicity posttherapy was the presence of baseline DJD and prolonged salvage ADT posttreatment for patients developing recurrence., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To report the long-term control and toxicity outcomes of patients with clinically localized prostate cancer, who underwent low-dose-rate prostate brachytherapy with magnetic resonance spectroscopic image (MRSI)-directed dose escalation to intraprostatic regions., Methods and Materials: Forty-seven consecutive patients between May 2000 and December 2003 were analyzed retrospectively. Each patient underwent a preprocedural MRSI, and MRS-positive voxels suspicious for malignancy were identified. Intraoperative planning was used to determine the optimal seed distribution to deliver a standard prescription dose to the entire prostate, while escalating the dose to MRS-positive voxels to 150% of prescription. Each patient underwent transperineal implantation of radioactive seeds followed by same-day CT for postimplant dosimetry., Results: The median prostate D90 (minimum dose received by 90% of the prostate) was 125.7% (interquartile range [IQR], 110.3-136.5%) of prescription. The median value for the MRS-positive mean dose was 229.9% (IQR, 200.0-251.9%). Median urethra D30 and rectal D30 values were 142.2% (137.5-168.2%) and 56.1% (40.1-63.4%), respectively. Median followup was 86.4 months (IQR, 49.8-117.6). The 10-year actuarial prostate-specific antigen relapse-free survival was 98% (95% confidence interval, 93-100%). Five patients (11%) experienced late Grade 3 urinary toxicity (e.g., urethral stricture), which improved after operative intervention. Four of these patients had dose-escalated voxels less than 1.0 cm from the urethra., Conclusions: Low-dose-rate brachytherapy with MRSI-directed dose escalation to suspicious intraprostatic regions exhibits excellent long-term biochemical control. Patients with dose-escalated voxels close to the urethra were at higher risk of late urinary stricture., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We provide a comprehensive analysis of anatomical patterns of recurrence following external beam radiotherapy in patients with localized prostate cancer., Materials and Methods: This retrospective analysis included 2,694 patients with localized prostate cancer who received definitive, dose escalated external beam radiotherapy from 1991 to 2008. First recurrence sites were defined as initial sites of clinically detected recurrence and any subsequent clinically detected recurrence within 3 months. Anatomical recurrence patterns were classified as local (prostate/seminal vesicles only), lymphotropic (lymph nodes only) and osteotropic (bones only) in patients with disease confined only to these respective sites for at least 2 years from the initial clinically detected recurrence., Results: Prostate was the most common first recurrence site in the low, intermediate and high risk groups with an 8-year cumulative incidence of 3.5%, 9.8% and 14.6%, respectively. The 8-year risk of isolated pelvic lymph node relapse as the first recurrence site was 0%, 1.0% and 3.3%, respectively. In the 474 patients with clinically detected recurrence the most common first recurrence site was local in 55.3%, bone in 33.5%, pelvic lymph nodes in 21.3% and abdominal lymph nodes in 9.1%. Patients showed unique relapse distributions, including a pattern that was local in 41.6%, lymphotropic in 9.7%, osteotropic in 20.3% and multiorgan/visceral in 28.5%. Anatomical recurrence pattern was the strongest predictor of prostate cancer specific mortality on multivariate analysis of patients with clinically detected recurrence., Conclusions: The most common first recurrence site after dose escalated external beam radiotherapy for prostate cancer is in the prostate and seminal vesicles in all risk groups. In contrast, patients treated without elective pelvic lymph node irradiation are at relatively low risk for isolated pelvic lymph node relapse. Recurrence patterns revealed a tropism for specific anatomical distributions with divergent prognoses, suggesting underlying biological differences among tumors., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The management of biochemical failure (BF) following external beam radiotherapy (EBRT) for prostate cancer is controversial, due to both the heterogeneous disease course following a BF and a lack of clinical trials in this setting., Objective: We sought to characterize the natural history and predictors of outcome for patients experiencing BF in a large cohort of men with localized prostate cancer undergoing definitive dose-escalated EBRT., Design, Setting, and Participants: This retrospective analysis included 2694 patients with localized prostate cancer treated with EBRT at a large academic center. Of these, 609 experienced BF, defined as prostate-specific antigen (PSA) nadir + 2 ng/ml. The median follow-up was 83 mo for all patients and 122 mo for BF patients., Intervention(s): All patients received EBRT at doses of 75.6-86.4 Gy., Outcome Measurements and Statistical Analysis: The primary objective of this study was to determine predictors of distant progression at the time of BF. Cox proportional hazards models were used in univariate and multivariate analyses of distant metastases (DM), and a competing risks method was used to analyze prostate cancer-specific mortality (PCSM)., Results and Limitations: From the date of BF, the median times to DM and PCSM mortality were 5.4 yr and 10.5 yr, respectively. Shorter posttreatment PSA doubling time, a higher initial clinical tumor stage, a higher pretreatment Gleason score, and a shorter interval from the end of radiotherapy to BF were independent predictors for clinical progression following BF. Patients with two of these risk factors had a significantly higher incidence of DM and PCSM following BF than those with zero or one risk factor. The main limitations of this study are its retrospective nature and heterogeneous salvage interventions., Conclusions: Clinical and pathologic factors can help identify patients at high risk of clinical progression following BF., Patient Summary: In this report, we look at predictors of outcome for patients with prostate cancer recurrence, as determined by prostate-specific antigen (PSA) levels, following radiation treatment. We found that the approximate median times to distant metastasis and death from prostate cancer for patients in this situation were 5 yr and 10 yr, respectively. Furthermore, we found that patients with a rapid increase in PSA levels following treatment, a short time to PSA recurrence, invasion of extraprostatic organs, or a high Gleason score had worse outcomes., Competing Interests: Financial disclosures: Michael J. Zelefsky certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the association between statin use and prostate cancer outcomes in intermediate- and high-risk patients treated with brachytherapy for prostate cancer., Methods and Materials: Between 1998 and 2010, 754 men with National Comprehensive Cancer Network intermediate- (n = 627) and high-risk (n = 127) prostate cancer were treated with prostate brachytherapy at our institution. Patients received either low-dose-rate or high-dose-rate brachytherapy as monotherapy or in combination with supplemental external beam radiotherapy. Two hundred eighty-five patients (37.8%) also received androgen-deprivation therapy. Two hundred seventy-three men (36.2%) were identified as taking statin medication before initiating radiation therapy. Prostate-specific antigen relapse-free survival (PSA-RFS), distant metastasis-free survival (DMFS), and overall survival were compared using log-rank tests. Associations of patient and treatment characteristics with outcomes were analyzed with univariate and multivariate regression. The median followup was 48 months., Results: The 8-year PSA-RFS for intermediate-risk, high-risk, and all patients was 92.2%, 64.1%, and 87.7%, respectively. The 8-year DMFS was 97.1%, 82.9%, and 94.9%, respectively. The 8-year overall survival for the entire cohort was 86.6%. There were no significant differences between statin users and nonusers when stratified by risk group, nor when analyzed as a full cohort. On multivariate analysis, Gleason score 4 + 3 = 7 and >7 were significantly associated with worse PSA-RFS (p ≤ 0.003 and <0.001, respectively). Gleason score > 7 (p = 0.008) and the use of neoadjuvant androgen-deprivation therapy (p = 0.03) was associated with worse DMFS. Statin use did not significantly impact PSA-RFS or DMFS., Conclusions: Pretreatment statin use is not associated with improved outcomes in intermediate- and high-risk patients undergoing prostate brachytherapy-based regimens for prostate cancer., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The purpose of this article is to present an updated set of American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of radiation therapy in postprostatectomy prostate cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Recent and relevant literature reviewed by the panel led to establishment of criteria for appropriate use of radiation therapy in postprostatectomy prostate cancer. The discussion includes treatment technique, appropriate dose, field design, and the role of prostate-specific antigen (PSA). Ratings and commentary of the panel on multiple treatment parameters were used to reach consensus. Patients with high-risk pathologic features benefit from postprostatectomy radiation therapy.

Study Design: A total of 40 patients with spinal metastases from renal cell carcinomas (RCCs) or prostate carcinomas (PCs) were studied using DCE-MRI (dynamic contrast-enhanced magnetic resonance imaging)., Objective: To evaluate spinal metastases from RCC and PC to assess the sensitivity and specificity of perfusion parameters obtained by quantitative and semiquantitative methods, which would allow for noninvasive discrimination between hypovascular and hypervascular lesions., Summary of Background Data: Conventional MRI can be inconclusive in assessing diagnostically complex spinal lesions in patients with cancer in whom fibrosis, infarction, edema related to compression fractures, and infection may simulate malignant neoplasm. Conventional MRI is also of limited value in assessing tumor vascularity and identifying hypervascular tumors. DCE-MRI offers an advantage over conventional MRI in that it provides anatomical, physiological, and hemodynamic information about neoplastic lesions., Methods: DCE perfusion parameters: vascular permeability, plasma volume (V(p)), wash-in slope, and peak-enhancement parameter were measured to assess their potential as discriminators of tumor vascularity. A Mann-Whitney U test (at P ≤ 0.01), was performed to quantify and compare significance of perfusion parameters between the 2 groups., Results: Of the 4 perfusion parameters studied, V(p) was observed to have the largest difference in mean (μ) between PC (μ = 3.29/s) and RCC metastases (μ = 5.92/s). This was followed by the peak-enhancement, vascular permeability, and wash-in parameters. A Mann-Whitney U test showed a significant difference between V(p) values for PC and RCC lesions (P ≤ 0.001). Similarly, peak-enhancement parameter showed a significant difference between the 2 histologies (P ≤ 0.001), as did vascular permeability (P ≤ 0.01). The receiver operating characteristic curve showed that V(p) recorded the highest area under the curve (0.867)., Conclusion: V(p) was shown to be the best discriminator between spinal metastases from PC and RCC with the mean V(p) of RCC metastasis being 1.8 times that of the PC lesions, thus discriminating between hyper- and hypovascular metastases, which has important clinical implications.

Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT)., Methods and Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC)., Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001)., Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To compare tumour control and toxicity outcomes with the use of high-dose intensity-modulated radiation therapy (IMRT) alone or brachytherapy combined with IMRT (combo-RT) for patients with intermediate-risk prostate cancer., Patients and Methods: Between 1997 and 2010, 870 consecutive patients with intermediate-risk prostate cancer were treated at our institution with either 86.4 Gy of IMRT alone (n = 470) or combo-RT consisting of brachytherapy combined with 50.4 Gy of IMRT (n = 400). Brachytherapy consisted of low-dose-rate permanent interstitial implantation in 260 patients and high-dose-rate temporary implantation in 140 patients. The median (range) follow-up for the entire cohort was 5.3 (1-14) years., Results: For IMRT alone vs combo-RT, 7-year actuarial prostate-specific antigen (PSA)-relapse-free survival (PSA-RFS) rates were 81.4 vs 92.0% (P < 0.001), and distant metastases-free survival (DMFS) rates were 93.0 vs 97.2% (P = 0.04), respectively. Multivariate analysis showed that combo-RT was associated with better PSA-RFS (hazard ratio [HR], 0.40 [95% confidence interval, 0.24-0.66], P < 0.001), and better DMFS (HR, 0.41 [0.18-0.92], P = 0.03). A higher incidence of acute genitourinary (GU) grade 2 (35.8 vs 18.9%; P < 0.01) and acute GU grade 3 (2.3 vs 0.4%; P = 0.03) toxicities occurred in the combo-RT group than in the IMRT-alone group. Most acute toxicity resolved. Late toxicity outcomes were similar between the treatment groups. The 7-year actuarial late toxicity rates for grade 2 gastrointestinal (GI) toxicity were 4.6 vs 4.1% (P = 0.89), for grade 3 GI toxicity 0.4 vs 1.4% (P = 0.36), for grade 2 GU toxicity 19.4 vs 21.2% (P = 0.14), and grade 3 GU toxicity 3.1 vs 1.4% (P = 0.74) for the IMRT vs the combo-RT group, respectively., Conclusions: Enhanced dose escalation using combo-RT was associated with superior PSA-RFS and DMFS outcomes for patients with intermediate-risk prostate cancer compared with high-dose IMRT alone at a dose of 86.4 Gy. While acute GU toxicities were more prevalent in the combo-RT group, the incidence of late GI and GU toxicities was similar between the treatment groups., (© 2013 The Authors. BJU International © 2013 BJU International.)

Purpose: To present the most updated American College of Radiology consensus guidelines formed from an expert panel on the appropriate use of external-beam radiation to manage stage T1 and T2 prostate cancer., Methods: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., Results: The panel summarized the most recent and relevant literature on the topic and voted on 3 clinical variants illustrating the appropriate dose, techniques, and use of adjuvant hormone therapy with external-beam radiation for low-risk, intermediate-risk, and high-risk prostate cancer. Numerical rating and commentary reflecting the panel consensus was given for each treatment approach in each variant., Conclusions: External-beam radiation is a key component of the curative management of T1 and T2 prostate cancer. By combining the most recent medical literature and expert opinion, this guideline can aid clinicians in the appropriate use of external-beam radiation for prostate cancer.

Purpose: We report the toxicity and biochemical tumor control outcome of a prospective Phase II study using high-dose-rate brachytherapy (HDR) alone as a salvage therapy for recurrent disease after external beam radiotherapy (EBRT)., Methods: Forty-two patients with biopsy-proven recurrence were enrolled on a Phase II study of salvage HDR monotherapy using iridium-192. Median pretreatment EBRT dose was 8100 cGy (6840-8640 cGy) and the median time from completion of EBRT to salvage HDR was 73 months. The protocol prescription dose of 3200 cGy was delivered in four fractions over 30 hours in a single insertion. Median followup after salvage HDR was 36 months (6-67 months)., Results: The actuarial prostate-specific antigen biochemical relapse-free survival and distant metastases-free survival rates at 5 years were 68.5% and 81.5%, respectively. Cause-specific survival was 90.3%. Late genitourinary Grade 1and 2 toxicities were found in 38% and 48%, respectively, and one patient developed Grade 3 urinary incontinence. Late Grade 1 and 2 gastrointestinal toxicity was noted in 17% and 8% of patients, respectively. Three patients (7%) developed Grade 2 late urinary toxicity (urethral stricture), which were corrected with urethral dilatation, and one patient developed Grade 3 urinary incontinence. No Grade 4 toxicities were observed., Conclusions: Genitourinary toxicity was the most commonly encountered toxicity observed after salvage HDR but severe toxicities were uncommon. Salvage HDR is an effective and well-tolerated modality for locally recurrent prostate cancer and should be considered even for patients who have previously been treated with ultra-high dose levels of EBRT., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: The management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification., Objective: We propose a new risk stratification system for intermediate-risk PCa to aid in prognosis and therapeutic decision making., Design, Setting, and Participants: Between 1992 and 2007, 1024 patients with National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy information were treated with definitive external-beam radiation therapy (EBRT) utilizing doses ≥ 81 Gy. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥ 50%, or multiple intermediate-risk factors (IRFs; cT2b-c, prostate-specific antigen [PSA] 10-20, or Gleason score 7)., Intervention: All patients received EBRT with ≥ 81 Gy with or without neoadjuvant and concurrent androgen-deprivation therapy (ADT)., Outcome Measurements and Statistical Analysis: Univariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a competing-risk method., Results and Limitations: Median follow-up was 71 mo. Primary Gleason pattern 4 (hazard ratio [HR]: 3.26; p<0.0001), PPBC ≥ 50% (HR: 2.72; p=0.0007), and multiple IRFs (HR: 2.20; p=0.008) all were significant predictors of increased DM in multivariate analyses. Primary Gleason pattern 4 (HR: 5.23; p<0.0001) and PPBC ≥ 50% (HR: 4.08; p=0.002) but not multiple IRFs (HR: 1.74; p=0.21) independently predicted for increased PCSM. Patients with UIR disease had inferior PSA-RFS (HR: 2.37; p<0.0001), DM (HR: 4.34; p=0.0003), and PCSM (HR: 7.39; p=0.007) compared with those with favorable intermediate-risk disease, despite being more likely to receive neoadjuvant ADT. Short follow-up and retrospective study design are the primary limitations., Conclusions: Intermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Stereotactic body radiotherapy (SBRT) is being used with increasing frequency as definitive treatment of early stage prostate cancer. Much of the justification for its adoption was derived from earlier clinical results using high-dose-rate (HDR) brachytherapy. We determine whether HDR's dosimetry can be achieved by virtual SBRT., Methods and Materials: Patients with intermediate-risk prostate cancer on a prospective trial evaluating the efficacy of HDR monotherapy treated to dose of 9.5Gy×4 fractions were used for this study. A total of 5 patients were used in this analysis. Virtual SBRT plans were developed to reproduce the planning target volume (PTV) HDR dose distributions. Both normal tissue- and PTV-prioritized plans were generated., Results: From the normal tissue-prioritized plan, HDR and virtual SBRT achieved similar PTV V100 (93.8% vs. 93.1%, p=0.20) and V150 (40.3% vs. 42.9%, p=0.69) coverage. However, the PTV V200 was not attainable with SBRT (15.2% vs. 0.0%, p<0.001). The rectal Dmax was significantly lower with HDR (94.2% vs. 99.42%, p=0.05). The rectal D2 cc was also lower (60.8% vs. 71.1%, p=0.07). Difference in D1 cc urethral dose was not significantly different (87.7% vs. 75.2%, p=0.33). Comparing the PTV-prioritized plans, the rectal Dmax (94.2% vs. 111.1%, p=0.05) and mean dose (27.1% vs. 33.3%, p=0.03) were significantly higher using SBRT, and the rectal D2 cc was higher using SBRT (60.8% vs. 81.8%, p=0.07)., Conclusions: HDR achieves significantly higher intraprostatic doses while achieving a lower maximum rectal dose compared with our virtual SBRT treatment planning. Future studies should compare clinical outcomes and toxicity between these modalities., (Copyright © 2013 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: To report long-term outcomes of men ≤60 years treated with brachytherapy (BT) for low- and intermediate-risk prostate cancer., Patients and Methods: Of 1655 patients treated with BT for clinically localized prostate cancer between January 1998 and May 2008 at Memorial Sloan-Kettering Cancer Center, 236 patients with National Comprehensive Cancer Network low- (n = 178) or intermediate-risk (n = 58) prostate cancer were ≤60 years old with a 3-year minimum follow-up, and represent the subjects of this report. Brachytherapy was given either as monotherapy (n = 169) or with external beam radiation therapy (EBRT; n = 67). Forty-four patients (19%) received neoadjuvant cytoreductive hormone therapy. The 'nadir+2' definition was used for prostate-specific antigen (PSA) recurrence. Common Terminology Criteria for Acute Events (CTCAE) v 3.0 was used to grade genitourinary (GU) and gastrointestinal (GI) toxicity. Potency was defined as the ability to obtain an erection suitable for intercourse or an International Index of Erectile Function score ≥ 22. The Kaplan-Meier method and Cox regression were used for statistical analysis. The median follow-up was 83 months., Results: The 8-year PSA relapse-free survival (RFS), cancer-specific and overall survival rates for the entire cohort were 96, 99 and 96%, respectively. For patients with low-risk disease, the 8-year PSA RFS rate was 97% and for intermediate-risk patients it was 94% (P = 0.34). There was no difference in PSA RFS between BT alone and combined therapy (P = 0.17). Late grade ≥ 2 GU and GI toxicity was 14 and 3%, respectively. Of 150 patients potent before treatment, 76 (51%) were potent at last follow-up, with 50/76 (66%) using no medication. There was no significant difference in post-treatment potency between BT alone and BT with EBRT (P = 0.74)., Conclusions: Brachytherapy provides patients aged ≤ 60 years with low- and intermediate-risk prostate cancer with excellent outcomes and has a low risk of significant long-term GU or GI morbidity. Erectile function is preserved in >50% of patients and the majority do not require erectile dysfunction medication., (© 2013 BJU International.)

Purpose: To analyze the effect of primary Gleason (pG) grade among a large cohort of Gleason 7 prostate cancer patients treated with external beam radiation therapy (EBRT)., Methods and Materials: From May 1989 to January 2011, 1190 Gleason 7 patients with localized prostate cancer were treated with EBRT at a single institution. Of these patients, 613 had a Gleason 7 with a minimum of a sextant biopsy with nonfragmented cores and full biopsy core details available, including number of cores of cancer involved, percentage individual core involvement, location of disease, bilaterality, and presence of perineural invasion. Median follow-up was 6 years (range, 1-16 years). The prognostic implication for the following outcomes was analyzed: biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM)., Results: The 8-year bRFS rate for pG3 versus pG4 was 77.6% versus 61.3% (P<.0001), DMFS was 96.8% versus 84.3% (P<.0001), and PCSM was 3.7% versus 8.1% (P=.002). On multivariate analysis, pG4 predicted for significantly worse outcome in all parameters. Location of disease (apex, base, mid-gland), perineural involvement, maximum individual core involvement, and the number of Gleason 3+3, 3+4, or 4+3 cores did not predict for distant metastases., Conclusions: Primary Gleason grade 4 independently predicts for worse bRFS, DMFS, and PCSM among Gleason 7 patients. Using complete core information can allow clinicians to utilize pG grade as a prognostic factor, despite not having the full pathologic details from a prostatectomy specimen. Future staging and risk grouping should investigate the incorporation of primary Gleason grade when complete biopsy core information is used., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy., Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis., Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM., Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To report prostate-specific antigen (PSA) relapse-free survival and treatment-related toxicity outcomes after combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for patients with clinically localized prostate cancer., Methods and Materials: Between 1998 and 2009, 229 patients were treated with HDR brachytherapy followed 3 weeks later by supplemental EBRT. The HDR brachytherapy boost consisted of three fractions of (192)Ir (5.5-7.5Gy per fraction), and EBRT consisted of intensity-modulated radiotherapy delivering an additional 45.0-50.4Gy directed to the prostate gland and seminal vesicles. Median follow-up was 61 months., Results: Seven-year PSA relapse-free survival for low-, intermediate-, and high-risk patients were 95%, 90%, and 57%, respectively (p<0.001). Among high-risk patients treated with biological equivalent doses in excess of 190Gy, 7-year PSA relapse-free survival was 81%. In multivariate analysis, Gleason scores of ≥8 predicted for increased risk of biochemical failure, whereas the use of short-term neoadjuvant androgen deprivation therapy did not influence tumor-control outcomes even among intermediate- or high-risk patients. Seven-year incidence of distant metastases for low-, intermediate-, and high-risk patients were 5%, 3%, and 17%, respectively. Seven-year incidence of late Grade 2 and 3 genitourinary toxicities were 22.1% and 4.9%, respectively and the 7-year incidence of Grade 2 and 3 gastrointestinal toxicities were 1% and 0.4%, respectively., Conclusion: HDR prostate brachytherapy in conjunction with supplemental EBRT results in excellent biochemical relapse-free survival rates with a low incidence of severe late genitourinary or gastrointestinal toxicities. The use of short-term neoadjuvant androgen deprivation did not influence long-term biochemical tumor control in this cohort., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: To report the incidence and excess risk of second malignancy (SM) development compared with the general population after external beam radiotherapy (EBRT) and brachytherapy to treat prostate cancer., Methods and Materials: Between 1998 and 2001, 1,310 patients with localized prostate cancer were treated with EBRT (n = 897) or brachytherapy (n = 413). We compared the incidence of SMs in our patients with that of the general population extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results data set combined with the 2000 census data., Results: The 10-year likelihood of SM development was 25% after EBRT and 15% after brachytherapy (p = .02). The corresponding 10-year likelihood for in-field SM development in these groups was 4.9% and 1.6% (p = .24). Multivariate analysis showed that EBRT vs. brachytherapy and older age were the only significant predictors for the development of all SMs (p = .037 and p = .030), with a trend for older patients to develop a SM. The increased incidence of SM for EBRT patients was explained by the greater incidence of skin cancer outside the radiation field compared with that after brachytherapy (10.6% and 3.3%, respectively, p = .004). For the EBRT group, the 5- and 10-year mortality rate was 1.96% and 5.1% from out-of field cancer, respectively; for in-field SM, the corresponding mortality rates were 0.1% and 0.7%. Among the brachytherapy group, the 5- and 10-year mortality rate related to out-of field SM was 0.8% and 2.7%, respectively. Our observed SM rates after prostate RT were not significantly different from the cancer incidence rates in the general population., Conclusions: Using modern sophisticated treatment techniques, we report low rates of in-field bladder and rectal SM risks after prostate cancer RT. Furthermore, the likelihood of mortality secondary to a SM was unusual. The greater rate of SM observed with EBRT vs. brachytherapy was related to a small, but significantly increased, number of skin cancers in the EBRT patients compared with that of the general population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To identify predictors of biochemical tumor control and present an updated prognostic nomogram for patients with clinically localized prostate cancer treated with brachytherapy., Methods and Materials: One thousand four hundred sixty-six patients with clinically localized prostate cancer were treated with brachytherapy alone or along with supplemental conformal radiotherapy. Nine hundred one patients (61%) were treated with Iodine-125 ((125)I) monotherapy to a prescribed dose of 144Gy, and 41 (4.5%) were treated with Palladium-103 ((103)Pd) monotherapy to a prescribed dose of 125Gy. In patients with higher risk features (n=715), a combined modality approach was used, which comprised (125)I or (103)Pd seed implantation or Iridium-192 high-dose rate brachytherapy followed 1-2 months later by supplemental intensity-modulated image-guided radiotherapy to the prostate., Results: The 5-year prostate-specific antigen relapse-free survival (PSA-RFS) outcomes for favorable-, intermediate-, and high-risk patients were 98%, 95%, and 80%, respectively (p<0.001). Multivariate Cox regression analysis identified Gleason score (p<0.001) and pretreatment PSA (p=0.04) as predictors for PSA tumor control. In this cohort of patients, the use of neoadjuvant and concurrent androgen deprivation therapy did not influence biochemical tumor control outcomes. In the subset of patients treated with (125)I monotherapy, D(90)>140Gy compared with lower doses was associated with improved PSA-RFS. A nomogram predicting PSA-RFS was developed based on these predictors and had a concordance index of 0.70., Conclusions: Results with brachytherapy for all treatment groups were excellent. D(90) higher than 140Gy was associated with improved biochemical tumor control compared with lower doses. Androgen deprivation therapy use did not impact on tumor control outcomes in these patients., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare biochemical outcomes and morbidity associated with iodine-125 ((125)I) and palladium-103 ((103)Pd) brachytherapy as part of combined modality therapy for clinically localized prostate cancer., Methods and Materials: Between October 2002 and December 2008, 259 patients underwent prostate brachytherapy ((125)I prescription dose, 110Gy: n=199; (103)Pd prescription dose, 100Gy: n=60) followed by external beam radiotherapy (median dose, 50.4Gy). Eighty-seven patients also received neoadjuvant androgen deprivation therapy. Toxicities were recorded with CTCAE v 3.0, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function questionnaires., Results: Overall, acute Grade ≥2 genitourinary toxicity occurred in 21% and 30% of patients treated with (125)I and (103)Pd, respectively (p=0.16). There were no significant differences in IPSS change or urinary quality-of-life scores between the isotopes at 4, 6, or 12 months (p=0.20, 0.21, and 1.0, respectively). IPSS resolution occurred at a median of 11 and 6 months for (125)I and (103)Pd patients, respectively (p=0.03). On multivariate analysis, only the use of neoadjuvant androgen deprivation therapy was predictive of time to IPSS resolution (p=0.046). Late Grade ≥2 gastrointestinal toxicity occurred in 7% of (125)I patients and 6% of patients treated with (103)Pd. Of 129 potent patients at baseline, there was better erectile function in patients who received (103)Pd (p=0.02); however, the followup was shorter for these patients. The 5-year prostate-specific antigen relapse-free survival for (125)I and (103)Pd patients was 95.2% and 98.2% (p=0.73), respectively., Conclusion: There were no differences in acute or long-term genitourinary or gastrointestinal toxicity between (125)I and (103)Pd in combined modality therapy for prostate cancer. There may be less erectile toxicity with the use of (103)Pd; however, additional followup of these patients is needed. There was no significant difference in 5-year prostate-specific antigen relapse-free survival between (103)Pd and (125)I., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Image-based radiation treatment planning and localization have contributed to better targeting of the prostate and sparing of normal tissues. Guidelines are needed to address radiation dose delivery, including patient setup and immobilization, target volume definition, treatment planning, treatment delivery methods, and target localization. Guidelines for external-beam radiation treatment planning have been updated and are presented here. The use of appropriate doses, simulation techniques, and verification of field setup are essential for the accurate delivery of radiation therapy. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., (Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: A well-established body of literature supports the use of high-dose-rate (HDR) brachytherapy as definitive treatment for localized prostate cancer. Most of the articles describe HDR as a boost with adjuvant external beam radiation, but there is a growing experience with HDR monotherapy., Methods and Materials: The American Brachytherapy Society has convened a group of expert practitioners and physicists to develop guidelines for the use of HDR in the management of prostate cancer. This involved an extensive literature review and input from an expert panel., Results: Despite a wide variation in doses and fractionation reported, HDR brachytherapy provides biochemical control rates of 85-100%, 81-100%, and 43-93% for low-, intermediate-, and high-risk prostate cancers, respectively. Severe toxicity is rare, with most authors reporting less than 5% Grade 3 or higher toxicity. Careful attention to patient evaluation for appropriate patient selection, meticulous technique, treatment planning, and delivery are essential for successful treatment., Conclusion: The clinical outcomes for HDR are excellent, with high rates of biochemical control, even for high-risk disease, with low morbidity. HDR monotherapy, both for primary treatment and salvage, are promising treatment modalities., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients., Objective: Identify predictors of biochemical tumor control and distant metastases-free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT., Design, Setting, and Participants: This retrospective analysis comprised 2551 patients with clinical stages T1-T3 PCa. Median follow-up was 8 yr, extending >20 yr., Intervention: Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo., Measurements: A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed., Results and Limitations: Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels < 70.2 Gy and 70.2-79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse-free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes., Conclusions: Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: : External beam radiation therapy is a standard of care treatment for men who present with clinically localized (T1-T2) prostate cancer. The purpose of this review was to provide clarification on the appropriateness criteria and management considerations for the treatment of prostate cancer with external beam radiation therapy., Methods: : A panel consisting of physicians with expertise on prostate cancer was assembled and provided with a number of clinical scenarios for consensus treatment and management guidelines. Prostate cancer patient vignettes were presented along with specific management recommendations based on an extensive review of the modern external beam radiotherapy literature. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances, where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment., Results: : Modern external beam radiation therapy series demonstrate favorable biochemical control rates for patients with localized prostate cancer. Morbidity profiles are also favorable and it is clear that this is enhanced by modern techniques like 3-dimensional conformal radiation therapy and intensity-modulated radiation therapy. An active area of investigation is evaluating the use of hypofractionated dosing., Conclusions: : Continued investigation to refine patient selection, external beam radiation technology application, and alternative dosing schedules should result in further improvements in biochemical outcome and decreased morbidity with external beam radiation treatment for localized prostate cancer.

Purpose: Permanent prostate brachytherapy has emerged as a standard of care treatment for approximately 50,000 men annually who present with clinically localized prostate cancer. The purpose of this review was to provide clarification on the appropriateness criteria and management considerations for the treatment of prostate cancer with permanent prostate brachytherapy., Methods: Panel members with expertise on prostate cancer were assembled and provided several clinical scenarios for consensus treatment and management guidelines. Prostate cancer patient vignettes were presented along with specific management recommendations based on an extensive review of the modern brachytherapy literature. The brachytherapy topic development and review consists of two parts which require extensive participation by the expert panel. The American College of Radiology (ACR) Appropriateness Criteria (AC) are derived from a multidisciplinary panel of experts from both the academic and private practice settings. The first activity is a review of the current literature with development of an evidence table, referenced narrative, and ratings table of treatments. The second activity is the consensus-building process using a modified Delphi technique via an anonymous voting process., Results: Most brachytherapy series have demonstrated favorable morbidity profiles and durable biochemical control rates for patients with low-, intermediate-, and high-risk features. However, as brachytherapy followups have matured, it has become increasingly apparent that efficacy and morbidity are highly dependent on implant quality., Conclusion: Continued attempts to refine patient selection, brachytherapy treatment planning philosophy, technique, and postimplant management should result in further improvements in biochemical outcome and decreased brachytherapy-related morbidity., (Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: The authors investigated long-term tumor control and toxicity outcomes after high-dose, intensity-modulated radiation therapy (IMRT) in patients who had clinically localized prostate cancer., Methods: Between April 1996 and January 1998, 170 patients received 81 gray (Gy) using a 5-field IMRT technique. Patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse, distant metastases, and cause-specific survival outcomes were calculated. The median follow-up was 99 months., Results: The 10-year actuarial prostate-specific antigen relapse-free survival rates were 81% for the low-risk group, 78% for the intermediate-risk group, and 62% for the high-risk group; the 10-year distant metastases-free rates were 100%, 94%, and 90%, respectively; and the 10-year cause-specific mortality rates were 0%, 3%, and 14%, respectively. The 10-year likelihood of developing grade 2 and 3 late genitourinary toxicity was 11% and 5%, respectively; and the 10-year likelihood of developing grade 2 and 3 late gastrointestinal toxicity was 2% and 1%, respectively. No grade 4 toxicities were observed., Conclusions: To the authors' knowledge, this report represents the longest followed cohort of patients who received high-dose radiation levels of 81 Gy using IMRT for localized prostate cancer. The findings indicated that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized prostate cancer., (Copyright © 2010 American Cancer Society.)

Objectives: To compare the long-term, prostate-specific antigen relapse-free survival outcome and incidence of toxicity for patients with low-risk prostate cancer who underwent brachytherapy or intensity-modulated radiotherapy (RT)., Methods: A total of 729 consecutive patients underwent brachytherapy (n = 448; prescription dose 144 Gy) or intensity-modulated RT alone (n = 281; prescription dose 81 Gy). The prostate-specific antigen relapse-free survival using the nadir plus 2 ng/mL definition and late toxicity using the National Cancer Institute's Common Terminology Criteria for Adverse Events were determined., Results: The 7-year prostate-specific antigen relapse-free survival rate for the brachytherapy and intensity-modulated RT groups was 95% and 89% for low-risk patients, respectively (P = .004). Cox regression analysis demonstrated that brachytherapy was associated with improved prostate-specific antigen relapse-free survival, even after adjustment for other variables. The incidence of metastatic disease between treatment sessions was low for both treatment groups. Late grade 2 gastrointestinal toxicity was observed in 5.1% and 1.4% of the brachytherapy and intensity-modulated RT groups, respectively (P = .02). No significant differences were seen between treatment groups for late grade 3 or greater rectal complications (brachytherapy 1.1% and intensity-modulated RT 0%; P = .19). Late grade 2 urinary toxicity occurred more often in the brachytherapy group than in the intensity-modulated RT group (15.6% and 4.3%, respectively; P < .0001). No significant differences were seen between the 2 treatment groups for late grade 3 urinary toxicity (brachytherapy 2.2% and intensity-modulated RT 1.4%; P = .62)., Conclusions: Among low-risk prostate cancer patients, the 7-year biochemical tumor control was superior for intraoperatively planned brachytherapy compared with high-dose intensity-modulated RT. Although significant toxicities were minimal for both groups, modest, but significant, increases in grade 2 urinary and rectal symptoms were noted for brachytherapy compared with intensity-modulated RT., (Published by Elsevier Inc.)

Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer., Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years., Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p=0.002). In a multivariate analysis, statin use (hazard ratio [HR] 0.69, p=0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p=0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p=0.51). On multivariate analysis, lower NCCN risk group (p=0.01) and ADT use (p=0.005) predicted improved DMFS., Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: We report on a retrospective comparison of biochemical outcomes using an ultra-high dose of conventionally fractionated intensity-modulated radiation therapy (IMRT) vs. a lower dose of IMRT combined with high-dose-rate (HDR) brachytherapy to increase the biologically effective dose of IMRT., Methods: Patients received IMRT of 86.4Gy (n=470) or HDR brachytherapy (21Gy in three fractions) followed by IMRT of 50.4Gy (n=160). Prostate-specific antigen (PSA) relapse was defined as PSA nadir+2. Median followup was 53 months for IMRT alone and 47 months for HDR., Results: The 5-year actuarial PSA relapse-free survival (PRFS) for HDR plus IMRT vs. ultra-high-dose IMRT were 100% vs. 98%, 98% vs. 84%, and 93% vs. 71%, for National Comprehensive Cancer Network low- (p=0.71), intermediate- (p<0.001), and high-risk (p=0.23) groups, respectively. Treatment (p=0.0006), T stage (p<0.0001), Gleason score (p<0.0001), pretreatment PSA (p=0.0037), risk group (p<0.0001), and lack of androgen-deprivation therapy (p=0.0005) were significantly associated with improved PRFS on univariate analysis. HDR plus IMRT vs. ultra-high-dose IMRT (p=0.0012, hazard ratio [HR]=0.184); age (p=0.0222, HR=0.965); and risk group (p<0.0001, HR=2.683) were associated with improved PRFS on multivariate analysis., Conclusion: Dose escalation of IMRT by adding HDR brachytherapy provided improved PRFS in the treatment of prostate cancer compared with ultra-high-dose IMRT, independent of risk group on multivariate analysis, with the most significant benefit for intermediate-risk patients., (Copyright © 2010 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To use radiation exposure rate measurements to determine patient-specific radiation safety instructions with the aim of reducing unnecessary precaution times and to evaluate potential doses to members of the public., Methods and Materials: Radiation exposure rate measurements were obtained from 1279 patients with Stage T1-2 prostate cancer who underwent transperineal (125)I or (103)Pd seed implantation from January 1995 through July 2008. An algorithm was developed from these measurements to determine the required precaution times to maintain public effective doses below 50% of the limits for specific exposure situations., Results: The median air kerma rates at 30 cm from the anterior skin surface were 4.9 microGy/h (range: 0.1-31.5) for (125)I and 1.5 microGy/h (range: 0.02-14.9) for (103)Pd. The derived algorithms depended primarily on the half-life T(p), the measured exposure rate at 30 cm, and specific exposure situation factors. For the typical (103)Pd patient, no radiation safety precautions are required. For the typical (125)I patient, no precautions are required for coworkers, nonpregnant adults who do not sleep with the patient, or nonpregnant adults who sleep with the patient. Typical (125)I patients should only avoid sleeping in the "spoon" position (i.e., in contact) with pregnant adults and avoid holding a child for long periods of time in the lap for about 2 months., Conclusions: The large number of cases available for this study permitted the development of an algorithm to simply determine patient-specific radiation safety instructions. The resulting precaution times are significantly less restrictive than those generally prescribed currently., ((c) 2010 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We assessed the effect of radical prostatectomy (RP) and external beam radiotherapy (EBRT) on distant metastases (DM) rates in patients with localized prostate cancer treated with RP or EBRT at a single specialized cancer center., Patients and Methods: Patients with clinical stages T1c-T3b prostate cancer were treated with intensity-modulated EBRT (> or = 81 Gy) or RP. Both cohorts included patients treated with salvage radiotherapy or androgen-deprivation therapy for biochemical failure. Salvage therapy for patients with RP was delivered a median of 13 months after biochemical failure compared with 69 months for EBRT patients. DM was compared controlling for patient age, clinical stage, serum prostate-specific antigen level, biopsy Gleason score, and year of treatment., Results: The 8-year probability of freedom from metastatic progression was 97% for RP patients and 93% for EBRT patients. After adjustment for case mix, surgery was associated with a reduced risk of metastasis (hazard ratio, 0.35; 95% CI, 0.19 to 0.65; P < .001). Results were similar for prostate cancer-specific mortality (hazard ratio, 0.32; 95% CI, 0.13 to 0.80; P = .015). Rates of metastatic progression were similar for favorable-risk disease (1.9% difference in 8-year metastasis-free survival), somewhat reduced for intermediate-risk disease (3.3%), and more substantially reduced in unfavorable-risk disease (7.8% in 8-year metastatic progression)., Conclusion: Metastatic progression is infrequent in men with low-risk prostate cancer treated with either RP or EBRT. RP patients with higher-risk disease treated had a lower risk of metastatic progression and prostate cancer-specific death than EBRT patients. These results may be confounded by differences in the use and timing of salvage therapy.

Purpose: To report the influence of posttreatment prostate-specific antigen (PSA) nadir response at 2 years after external beam radiotherapy (RT) on distant metastases (DM) and cause-specific mortality (CSM)., Methods and Materials: Eight hundred forty-four patients with localized prostate cancer were treated with conformal RT. The median duration of follow-up was 9.1 years. A fixed landmark time point at 2 years was used to assess the influence of nadir PSA value as a time-dependent variable on long-term outcomes., Results: Multivariate analysis demonstrated that nadir PSA

Purpose: To report prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival (DMFS) outcomes for patients with clinically localized prostate cancer treated with high-dose conformal radiotherapy., Methods and Materials: Between 1988 and 2004, a total of 2,047 patients with clinically localized prostate cancer were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Prescribed dose levels ranged from 66-86.4 Gy. Median follow-up was 6.6 years (range, 3-18 years)., Results: Although no differences were noted among low-risk patients for the various dose groups, significant improvements were observed with higher doses for patients with intermediate- and high-risk features. In patients with intermediate-risk features, multivariate analysis showed that radiation dose was an important predictor for improved PSA relapse-free survival (p < 0.0001) and improved DMFS (p = 0.04). In patients with high-risk features, multivariate analysis showed that the following variables predict for improved PSA relapse-free survival: dose (p < 0.0001); age (p = 0.0005), and neoadjuvant-concurrent androgen deprivation therapy (ADT; p = 0.01). In this risk group, only higher radiation dose was an important predictor for improved DMFS (p = 0.04)., Conclusions: High radiation dose levels were associated with improved biochemical tumor control and decreased risk of distant metastases. For high-risk patients, despite the delivery of high radiation dose levels, the use of ADT conferred an additional benefit for improved tumor control outcomes. We observed a benefit for ADT in high-risk patients who received higher doses.

Objective: To report the long-term tumor control and survival outcomes after conformal external-beam radiotherapy for patients with clinical stage T3 prostate cancer., Methods: Between 1988 and 2000, 296 patients with clinical stage T3 prostate cancer were treated with three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Of these, 130 patients (44%) had stage T3a (extracapsular extension without seminal vesicle involvement [SVI]) and 166 patients (56%) had stage T3b disease (SVI). Prior to radiotherapy, 189 patients (43%) were treated with short-course androgen-deprivation therapy (ADT). The median follow-up time was 8 yr., Results: The 5- and 10-yr prostate-specific antigen (PSA) relapse-free survival (PRFS) outcomes for stage T3a tumors were 69% and 44%, respectively. The corresponding PRFS outcomes for T3b tumors were 49% and 32% (p=0.005). Despite the presence of locally advanced disease, the 5- and 10-yr local progression-free survival (LPFS) outcomes for all patients were 87% and 83%. Among patients who received > or =8100 cGy and ADT, the 5- and 10-yr local control rates were 96% and 88%. The 5- and 10-yr distant metastases-free survival (DMFS) outcomes for stage T3a tumors were 85% and 73%. The corresponding DMFS outcomes for T3b tumors were 49% and 32% (p=0.005). Multivariate analysis demonstrated that ADT conferred a 7-fold risk reduction for local failure. Pretreatment PSA levels and the presence of SVI on clinical staging were important predictors of distant metastases., Conclusions: Conformal radiotherapy for T3 prostate cancer is associated with excellent tumor control and survival outcomes. These results are at least comparable to reported outcomes from surgical series for T3 disease and substantiate the role of radiotherapy as the standard management option for locally advanced stage prostate cancer.

Purpose: To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy (IMRT) to a dose of 86.4 Gy for localized prostate cancer., Methods and Materials: Between August 1997 and March 2004, 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique. To adhere to normal tissue constraints, the mean D95 and V100 for the planning target volume were 83 Gy and 87%, respectively. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse was calculated. The median follow-up was 53 months., Results: Thirty-seven patients (8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. There was no acute Grade 3 or 4 GI toxicity. One hundred and five patients (22%) experienced acute Grade 2 genitourinary (GU) toxicity and three patients (0.6%) had Grade 3 GU toxicity. There was no acute Grade 4 GU toxicity. Sixteen patients (3%) developed late Grade 2 GI toxicity and two patients (<1%) developed late Grade 3 GI toxicity. Sixty patients (13%) had late Grade 2 GU toxicity and 12 (<3%) experienced late Grade 3 GU toxicity. The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98%, 85% and 70% for the low, intermediate, and high risk NCCN prognostic groups., Conclusion: This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.

Purpose: To report the incidence and predictors of treatment-related toxicity at 10 years after three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for localized prostate cancer., Methods and Materials: Between 1988 and 2000, 1571 patients with stages T1-T3 prostate cancer were treated with 3D-CRT/IMRT with doses ranging from 66 to 81 Gy. The median follow-up was 10 years. Posttreatment toxicities were all graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events., Results: The actuarial likelihood at 10 years for the development of Grade>or=2 GI toxicities was 9%. The use of IMRT significantly reduced the risk of gastrointestinal (GI) toxicities compared with patients treated with conventional 3D-CRT (13% to 5%; p<0.001). Among patients who experienced acute symptoms the 10-year incidence of late toxicity was 42%, compared with 9% for those who did not experience acute symptoms (p<0.0001). The 10-year incidence of late Grade>or=2 genitourinary (GU) toxicity was 15%. Patients treated with 81 Gy (IMRT) had a 20% incidence of GU symptoms at 10 years, compared with a 12% for patient treated to lower doses (p=0.01). Among patients who had developed acute symptoms during treatment, the incidence of late toxicity at 10 years was 35%, compared with 12% (p<0.001). The incidence of Grade 3 GI and GU toxicities was 1% and 3%, respectively., Conclusions: Serious late toxicity was unusual despite the delivery of high radiation dose levels in these patients. Higher doses were associated with increased GI and GU Grade 2 toxicities, but the risk of proctitis was significantly reduced with IMRT. Acute symptoms were a precursor of late toxicities in these patients.

Purpose: To report the acute and late treatment-related toxicities of combined permanent interstitial (125)I implantation delivered via real-time intraoperative planning and supplemental intensity-modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer., Methods and Materials: One hundred twenty-seven patients were treated with a combined modality (CM) regimen consisting of (125)I implantation (110Gy) using a transrectal ultrasound-guided approach followed 2 months later by 50.4Gy of IMRT directed to the prostate and seminal vesicles. Late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events toxicity scale. The acute and late toxicities were compared to a contemporaneously treated cohort of 216 patients treated with (125)I alone to a prescribed dose of 144Gy., Results: The incidence of Grade 2 acute rectal and urinary side effects was 1% and 10%, respectively, and 2 patients developed Grade 3 acute urinary toxicities. The 4-year incidence of late Grade 2 gastrointestinal toxicity was 9%, and no Grade 3 or 4 complications have been observed. The 4-year incidence of late Grade 2 gastrourinary toxicities was 15% and 1 patient developed a Grade 3 urethral stricture, which was corrected with urethral dilatation. The percentage of patients who experienced resolution of late rectal and urinary symptoms was 92% and 65%, respectively. Multivariate analysis revealed that in addition to higher baseline International Prostate Symptom Score, those patients treated with implant alone compared to CM were more likely to experience Grade 2 acute urinary symptoms. Increased Grade 2 late rectal toxicities were noted for CM patients (9% vs. 1%; p=0.001) as well as a significant increase for late Grade 2 urinary toxicities (15% vs. 9%; p=0.004)., Conclusions: Adherence to dose constraints with combination real-time brachytherapy using real-time intraoperative planning and IMRT is associated with a low incidence of acute and late toxicities. Acute urinary side effects were significantly less common for CM patients compared to those treated with implantation alone. Late Grade 2 rectal and urinary toxicities were more common for patients treated with CM compared to implant alone.

Purpose: To report the dosimetric outcome of patients with clinically localized prostate cancer treated with I-125 permanent implantation using an intraoperative real-time conformal planning technique., Methods and Materials: Five hundred and sixty-two patients with prostate cancer were treated with I-125 permanent interstitial implantation using a transrectal ultrasound-guided approach. Real-time intraoperative treatment planning software that incorporates inverse planning optimization was used. Dose-volume constraints for this inverse-planning system included: prostate V100 >or=95%, maximal urethral dose or=140 Gy was achieved. In these patients, the V100 and D90 values did not have a significant influence on PSA relapse-free survival outcomes. The median maximum rectal dose and urethral doses were 104 Gy (72% of the prescription dose) and 187 Gy (130% of the prescription dose). The average and maximum rectal doses exceeding 100% of the prescription dose were less than 1% and 10% of patients, respectively. Average and maximum urethral doses exceeding 150% of the prescription dose were noted in 3% and 24% of patients, respectively. Average and maximum urethral doses exceeded 120% of the prescription dose in 21% and 58% of patients, respectively. Among patients where >or=2.5 cm(3) of the rectum was exposed to the prescription dose, the incidence of late grade 2 toxicity rectal toxicity was 9% compared to 4% for smaller volumes of the rectum exposed to similar doses (p=0.003). No dosimetric parameter in these patients with tight dose confines for the urethra influenced acute or late urinary toxicity., Conclusion: Real-time intraoperative planning was associated with a 90% consistency of achieving the planned intraoperative dose constraints for target coverage and maintaining planned urethral and rectal constraints in a high percentage of implants. Rectal volumes of >or=2.5 cm(3) exposed to the prescription doses were associated with an increased incidence of grade 2 rectal bleeding. Further enhancements in imaging guidance for optimal seed deposition are needed to guarantee optimal dose distribution for all patients. Whether such improvements lead to further reduction in acute and late morbidities associated with therapy requires further study.

Purpose: To report the 5-year tumor control and toxicity outcomes for patients with localized prostate treated with I-125 permanent implantation using an intraoperative real-time conformal planning technique., Methods and Materials: Between January 1998 and June 2002, 367 patients with prostate cancer were treated with I-125 permanent interstitial implantation using a transrectal ultrasound-guided approach. Real-time intraoperative treatment planning which incorporated inverse planning optimization was used. The median follow-up time was 63 months., Results: The median V100 and D90 were 96% and 173 Gy, respectively. In 96% of cases a D90 of >140 Gy was achieved. The median urethral and rectal doses were 100% and 33% of the prescription doses, respectively. The 5-year PSA relapse-free survival outcomes for favorable and intermediate risk patients according to the ASTRO definition were 96% and 89%, respectively. In these patients no dosimetric parameter was identified which influenced the biochemical outcome. Of 38% who developed acute Grade 2 urinary symptoms, 63% had resolution of their symptoms within a median time of 6 months. The incidence of late rectal and urinary Grade 3 or higher toxicities were 1% and 4%, respectively. Seven percent (n = 27) developed late rectal bleeding (Grade 2) and 19% experienced late Grade 2 urinary symptoms., Conclusion: Real-time intraoperative planning consistently achieved optimal coverage of the prostate with the prescription dose with concomitant low doses delivered to the urethra and rectum. Biochemical control outcomes were excellent at 5 years and late toxicity was unusual. These data demonstrate that real-time planning methods can consistently and reliably deliver the intended dose distribution to achieve an optimal therapeutic ratio between the target and normal tissue structures.

Purpose: We report on the long-term results and late toxicity outcomes of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer., Materials and Methods: Between 1996 and 2000 a total of 561 patients with clinically localized prostate cancer were treated with intensity modulated radiation therapy. All patients were treated to a dose of 81 Gy prescribed to the planning target volume. Prostate specific antigen relapse was defined according to the American Society for Therapeutic Radiology and Oncology consensus and Houston definitions (absolute nadir plus 2 ng/ml dated at the call). Median followup was 7 years (range 5 to 9)., Results: The 8-year actuarial PSA relapse-free survival rates for patients in favorable, intermediate and unfavorable risk groups according to the American Society for Therapeutic Radiology and Oncology definition were 85%, 76% and 72%, respectively (p <0.025). The 8-year actuarial prostate specific antigen relapse-free survival rates for patients in favorable, intermediate and unfavorable risk groups according to the Houston definition were 89%, 78% and 67%, respectively (p = 0.0004). The 8-year actuarial likelihood of grade 2 rectal bleeding was 1.6%. Three patients (0.1%) experienced grade 3 rectal toxicity requiring either 1 or more transfusions or a laser cauterization procedure. No grade 4 rectal complications have been observed. The 8-year likelihood of late grade 2 and 3 (urethral strictures) urinary toxicities were 9% and 3%, respectively. Among patients who were potent before intensity modulated radiation therapy, erectile dysfunction developed in 49%. The cause specific survival outcomes for favorable, intermediate and unfavorable risk cases were 100%, 96% and 84%, respectively., Conclusions: These long-term results confirm our previous observations regarding the safety of high dose intensity modulated radiation therapy for clinically localized prostate cancer. Despite the application of high radiation doses, the incidence of rectal bleeding at 8 years was less than 2%. Despite the increased conformality of the dose distribution associated with intensity modulated radiation therapy, excellent long-term tumor control outcomes were achieved.

Purpose: To report PSA relapse-free survival and toxicity outcomes of prostate cancer patients who have undergone three-dimensional computer-optimized high-dose-rate (HDR) brachytherapy with external beam radiotherapy as definitive treatment., Methods and Materials: One hundred five patients consecutively treated between 1998 and 2004 are reported. All patients were treated with HDR boost with lr 192 (5.5-7.0 Gy), based upon postimplant CT three-dimensional treatment planning using an in-house treatment plan optimization algorithm. Three-dimensional conformal external beam radiotherapy (45-50.4 Gy) was also administered 3 weeks after the HDR procedure. Toxicity was measured using National Cancer Institutes Common Toxicity Criteria and International Prostate Symptom Score indices., Results: With a median followup of 44 months (8-79 months), the 5-year PSA relapse-free survival outcomes for low, intermediate and high-risk patients were 100%, 98%, and 92%, respectively, Median urinary toxicity, and 93% of patients denied rectal problems at the time of last followup. Erectile dysfunction was noted in 47% patients at the time of last followup, but overall 80% were able to achieve vaginal penetration when those who responded to sildenafil were included., Conclusion: Computer-optimized three-dimensional HDR prostate brachytherapy provides excellent disease control for even high risk localized prostate cancer. Significant toxicity has been minimal.

Purpose: To validate radiation safety instructions to patients and to evaluate the potential radiation doses to members of the public after (125)I or (103)Pd prostate implantation., Methods and Materials: Radiation dose rate measurements were made in the immediate postoperative period on 636 consecutive patients with stage T1-T2 prostate cancer who underwent transperineal (125)I or (103)Pd implantation at Memorial Sloan-Kettering Cancer Center during the period from August 1995 through January 2003., Results: The mean radiation dose rate at the anterior skin surface following a prostate implant was 37 microSv/hr for (125)I and 8 microSv/hr for (103)Pd. At 30 cm from the anterior skin surface, these dose rates were reduced to 6 microSv/hr for (125)I and 3 microSv/hr for (103)Pd. At 1 m from the anterior skin surface the dose rates from both types of implants were reduced to less than 1 microSv/hr. The effect of body weight on dose rates from (125)I sources was examined for a select sub-group of patients and the measured dose rate was found to decrease with increasing body weight. In another group of patients, dose rate measurements were made on both lateral skin surfaces and were less than 16.8 microSv/hr in all cases. Assuming a 33% occupancy factor and utilizing the mean measured dose rate for (125)I, the time required to reach an effective dose equivalent limit of 5 mSv for caregivers was estimated to be 19 days on contact with the skin surface. Using a similar calculation, the lifetime doses for (125)I at a distance of 30 cm from the anterior skin surface, as well as the lifetime doses for (103)Pd on contact with the skin surface and at 30 cm from the anterior skin surface can be shown to be less than 5 mSv., Conclusions: The large number of cases available for this study permits a validation of radiation safety recommendations and provides concrete information from which the permitted exposure times following implantation can be estimated. The data support the conclusion that patients treated with these implants do not represent a radiation risk to members of the public.

The purpose of this study was to prospectively evaluate intraoperative prostatic edema during prostate brachytherapy with real-time ultrasound imaging and assess its impact upon the postimplant dosimetry of computer-optimized intraoperatively planned patients. Fifty consecutive patients with early-stage favorable risk adenocarcinoma of the prostate underwent transperineal ultrasound-guided I125 brachytherapy. Ultrasound volume studies of the prostate were performed immediately before and after placement of brachytherapy needles in the operating room. Twenty-five patients underwent intraoperative computer-optimized treatment planning using a genetic algorithm. Twenty-five patients underwent preimplant ultrasound studies for preimplant treatment planning. Postimplant dosimetry was performed on computed tomography scans obtained after the implant. Statistical analysis was performed taking into account patient age, preneedle volume, increase in intraoperative edema, use of hormonal therapy, type of isotope, number of needles or seeds used, and seed activity. For the intraoperatively planned patients, a median increase of 30% in intraoperative volume was found for the entire group. No correlation between the extent of intraoperative edema and %D90 (percentage of prescribed dose that covers 90% of the target volume) was found. None of the other analyzed variables correlated with %D90. Patients whose treatment was planned preoperatively experienced a median increase of 18.4% in target volume. A negative correlation between the amount of edema and the %D90 was found to be statistically significant (-0.55, P = 0.0047). All patients who underwent prostate brachytherapy experienced intraoperative prostatic edema. When planned intraoperatively, the amount of edema had no impact on the %D90. This may be because of the ability of intraoperative computer-optimized treatment planning to account for edema related to the procedure. Preplanned patients who encountered a greater degree of intraoperative edema had less %D90 target coverage.

Purpose: We have developed an intraoperative three-dimensional (3D) conformal treatment planning system for permanent prostate implantation in an effort to reduce toxicity further and improve the accuracy of this procedure. We report the preliminary outcome of patients with localized prostate cancer treated with this approach., Methods and Materials: Two hundred forty-eight patients with clinically localized prostate cancer were treated with transperineal ultrasound-guided permanent prostate implantation using a real-time intraoperative 3D conformal technique (I-3D) between 1997 and 2001. A genetic algorithm optimization program intraoperatively evaluated the dose deposited throughout the entire 3D volume for multiple seed configurations to identify which seed-loading pattern adhered best to the predetermined target, urethral and rectal dose constraints. The median follow-up time in these patients was 27 months (range 12-51). The dosimetric outcome and acute toxicity profile of these 248 patients were compared with those of patients who were treated between 1988 and 1996 at our institution with a preplanned transperineal implantation technique (PP)., Results: Postimplantation dosimetric analysis of the I-3D group demonstrated that the median value of the percentage of the target volume treated to at least the prescription dose (V(100)) was 96%, and the target coverage with the prescription dose (PD) was

Purpose: To report the acute and late toxicity and preliminary biochemical outcomes in 772 patients with clinically localized prostate cancer treated with high-dose intensity-modulated radiotherapy (IMRT)., Methods and Materials: Between April 1996 and January 2001, 772 patients with clinically localized prostate cancer were treated with IMRT. Treatment was planned using an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. A total of 698 patients (90%) were treated to 81.0 Gy, and 74 patients (10%) were treated to 86.4 Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined according to The American Society of Therapeutic Radiation Oncology Consensus Statement. The median follow-up time was 24 months (range: 6-60 months)., Results: Thirty-five patients (4.5%) developed acute Grade 2 rectal toxicity, and no patient experienced acute Grade 3 or higher rectal symptoms. Two hundred seventeen patients (28%) developed acute Grade 2 urinary symptoms, and one experienced urinary retention (Grade 3). Eleven patients (1.5%) developed late Grade 2 rectal bleeding. Four patients (0.1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 3-year actuarial likelihood of >/= late Grade 2 rectal toxicity was 4%. Seventy-two patients (9%) experienced late Grade 2 urinary toxicity, and five (0.5%) developed Grade 3 urinary toxicity (urethral stricture). The 3-year actuarial likelihood of >/= late Grade 2 urinary toxicity was 15%. The 3-year actuarial PSA relapse-free survival rates for favorable, intermediate, and unfavorable risk group patients were 92%, 86%, and 81%, respectively., Conclusions: These data demonstrate the feasibility of high-dose IMRT in a large number of patients. Acute and late rectal toxicities seem to be significantly reduced compared with what has been observed with conventional three-dimensional conformal radiotherapy techniques. Short-term PSA control rates seem to be at least comparable to those achieved with three-dimensional conformal radiotherapy at similar dose levels. Based on this favorable risk:benefit ratio, IMRT has become the standard mode of conformal treatment delivery for localized prostate cancer at our institution.