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OBJECTIVES To determine the location and grade of prostate cancer diagnosed by transperineal template-guided mapping (TTMB) after negative transrectal ultrasound-guided (TRUS) biopsy. MATERIALS AND METHODS This analysis consisted of 1118 consecutive patients who underwent TTMB from January 2005 to August 2015. Eight hundred thirty-five underwent TTMB after at least 1 negative TRUS biopsy and 283 underwent TTMB as the first biopsy procedure. The study population was divided into cohorts based on the number of prior TRUS biopsy sessions (0, 1, 2, and ≥3). No patient underwent multiparametric magnetic resonance imaging. Differences in location and cancer grade detected on TTMB were evaluated as a function of the number of prior TRUS biopsies. RESULTS Of the 1118 patients, 679 were diagnosed with prostate cancer. This included 208, 325, 104, and 42 patients who underwent 0, 1, 2, and ≥3 prior TRUS biopsies. The incidence of cancer detection on TTMB decreased as the number of prior TRUS biopsies increased (73.5% vs. 62.4% vs. 51.7% vs. 37.2%, P

Brachytherapy is a radiation therapy method in which radionuclide sources are used to deliver a radiation dose at a distance of up to a few centimeters by surface, intracavitary, intraluminal, or interstitial application. This practice parameter refers only to the use of radionuclides for brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer. High-dose-rate (HDR) brachytherapy uses radionuclides such as iridium-192 at dose rates of 20 cGy per minute (12 Gy per hour) or more to a designated target point or volume. High-dose-rate (HDR) brachytherapy is indicated for treating malignant or benign tumors where the treatment volume or targeted points are defined and accessible.

We determined the incidence of cancer detection by transperineal template guided mapping biopsy of the prostate in patients with at least 1 previously negative transrectal ultrasound guided biopsy.From January 2005 to January 2012 at least 1 negative transrectal ultrasound guided biopsy was done in 485 patients in our clinical database before proceeding with transperineal template guided mapping biopsy. No study patient had a previous prostate cancer diagnosis. The incidence of patients with 1, 2, or 3 or greater previous transrectal ultrasound guided biopsies was 55.3%, 25.9% and 18.8%, respectively. Transperineal template guided mapping biopsy was done in 74.8% of patients for increasing or occasionally persistently increased prostate specific antigen, in 19.4% for atypical small acinar proliferation and in 5.8% for high grade prostatic intraepithelial neoplasia.For the entire study population a median of 59 cores was submitted at transperineal template guided mapping biopsy. Cancer was ultimately detected in 226 patients (46.6%) using the transperineal template guided method, including 196 (86.7%) with clinically significant disease according to the Epstein criteria. The most common cancer detection site on transperineal template guided mapping biopsy was the anterior apex.Transperineal template guided mapping biopsy detected clinically significant prostate cancer in a substantial proportion of patients with negative transrectal ultrasound guided biopsy. This technique should be strongly considered in the context of increasing prostate specific antigen with failed confirmation of the tissue diagnosis.

Purpose To evaluate the effect of primary Gleason pattern on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) in Gleason 7 prostate cancer patients treated with low-dose-rate (LDR) interstitial brachytherapy with or without supplemental external beam radiation therapy and androgen deprivation therapy. Methods and Materials We retrospectively reviewed the medical records of 932 consecutive patients with biopsy-confirmed Gleason 7 prostate cancer who received LDR interstitial brachytherapy as a component of their definitive treatment regimen. Treatment outcomes were compared between patients with primary Gleason pattern 3 and 4. Results With a median followup of 7.4 years, the 10- and 14-year bPFS, CSS, and OS for the entire Gleason 7 study group were 95.7/95.7%, 98.6/98.6% and 77.2/64.3%, respectively. When biochemical control was evaluated as a function of primary Gleason pattern, the primary pattern 3 had a statistically higher 10- and 14-year bPFS (97.8/97.8% vs. 93.1/93.1%, p = 0.006). The Gleason pattern 3 patients also trended toward a higher 10- and 14-year CSS (99.3/99.3% vs. 96.9/96.9%, p = 0.058). OS was not statistically different between the two Gleason 7 cohorts. Conclusions Gleason 7 prostate cancer patients treated with LDR interstitial brachytherapy have an excellent long-term outcome. There was a small but statistically significant advantage in bPFS and a trend toward improved CSS in patients with a primary Gleason pattern of 3.

Transperineal permanent brachytherapy is a safe and effective treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and the American Brachytherapy Society (ABS) has produced practice parameters for LDR prostate brachytherapy. These practice parameters define the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrist. Factors with respect to patient selection and appropriate use of supplemental treatment modalities such as external beam radiation and androgen suppression therapy are discussed. Logistics with respect to the brachytherapy implant procedure, the importance of dosimetric guidelines, and attention to radiation safety procedures and documentation are presented. Adherence to these parameters can be part of ensuring quality and safety in a successful prostate brachytherapy program.

Purpose To evaluate outcome in the most unfavorable subset of high-risk prostate cancer patients treated with a combination of supplemental external beam radiation therapy (EBRT) and brachytherapy. Methods and Materials Very high-risk prostate cancer was defined as follows: any Gleason score 10, Gleason score 8–9 with >50% of the biopsy cores positive for malignancy, Gleason score 8–9 with a prostate-specific antigen (PSA) >20 ng/mL, any clinical stage T3, or any PSA >40 ng/mL. One hundred thirty-one patients were identified who met the aforementioned criteria. The median followup was 6.6 years. One hundred twenty (91.6%) patients received supplemental EBRT and 100 (76.4%) received androgen deprivation therapy (median duration, 19.5 months; range, 4–36 months). The median postimplant day 0 D90 (i.e., the minimum percentage of the prescription dose that covers the planning target volume) was 121.9% of prescription dose. Multiple clinical treatment and dosimetric parameters were evaluated for impact on the evaluated survival parameters. Results The median pretreatment PSA and Gleason score were 11.0 ng/mL and 8. One hundred ten (84%) patients had a Gleason score ≥8. At 9 and 12 years, the cause-specific survival, biochemical progression-free survival, and overall survival were 91.0% and 86.5%, 87.3% and 87.3%, and 70.5% and 60.5%, respectively. The most common cause of death was heart disease (22.2%) with deaths from nonprostate cancer (12.7%) and prostate cancer (8.3%) being less likely. Conclusions Permanent interstitial brachytherapy usually with supplemental EBRT and androgen deprivation therapy results in excellent biochemical control and cause-specific survival in the most unfavorable subset of high-risk prostate cancer patients. Death from diseases of the heart was more than twice as likely as death from prostate cancer.

Purpose To determine whether adverse pathologic features, including tumor grade and percent positive biopsy (PPB) cores, predict for prostate size reduction after neoadjuvant cytoreductive therapy. Methods and Materials Eighty-two consecutive patients who were diagnosed with prostate cancer by transperineal template–guided mapping biopsy (TTMB) received neoadjuvant cytoreductive therapy. The median number of biopsy cores was 59. Thirty patients received a leutinizing hormone–releasing hormone agonist and bicalutamide, whereas 52 patients received bicalutamide (50 mg daily) and dutasteride (0.5 mg daily). A transrectal ultrasound volumetric study of the prostate gland and ellipsoid volume determinations of the prostate gland and transition zone (TZ) were obtained immediately before TTMB and at 90 days (±7 days) after the initiation of neoadjuvant medical therapy. Univariate and multivariate regression analyses were performed to identify predictors of prostate gland and TZ volume reduction. Results At TTMB, the mean prostate volumetric and ellipsoid volumes were 55.4 cm3 and 49.0 cm3, respectively. After neoadjuvant medical therapy, the mean volumetric and ellipsoid prostate volumes were 30.8 cm3 and 28.5 cm3, respectively. On average, the prostate volume decreased by 43.9% and 41.0% on volumetric and ellipsoid measurements, respectively. The TZ volume decreased from 19.8 cm3 to 10.1 cm3 (mean volume reduction of 47.7%). In multivariate analysis, prostate volume cytoreduction was most closely associated with PPB (p = 0.014), TTMB prostate volume (p = 0.01), and drug regimen (p = 0.001). Conclusions The degree of prostate volume cytoreduction was positively associated with higher Gleason score and PPBs. Greater reductions in prostate volume may be an indicator of more aggressive cancer.

Purpose The management of patients diagnosed with thymoma remains unclear. This report attempts to identify the impact of adjuvant radiotherapy on overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with thymoma. Methods and Materials Patients diagnosed with thymic malignancy between 1973 and 2003 were retrospectively identified from centers participating in the Surveillance, Epidemiology, and End Results (SEER) program. Those patients classified as having thymic carcinoma were excluded from this analysis. OS and CSS were estimated by the Kaplan-Meier method. Outcomes for patients treated with and without radiation therapy were compared using the log-rank test. Multivariate analysis was performed with the Cox proportional hazards model to analyze factors predictive of OS and CSS. Results A total of 1,464 patients were identified as having thymic malignancy, and of these, 1,254 patients were identified as having malignant thymoma. The median follow-up time was 41 months (range, 4–337 months). Among patients who did not receive radiotherapy (RT), the 10-year rate of OS was 41% compared to 42% for those who did receive RT ( p = 0.06). The median OS for the patients who did not receive RT was 80 months compared to 97 months for those who did receive RT. In patients with Masaoka stage II–III malignancy, OS was significantly improved with RT ( p = 0.002), and a trend in improved CSS was observed ( p = 0.1). Patients were also analyzed based on resection status. For those patients who had an incomplete excision, the 10-year OS was 63% with RT and 46% without RT ( p = 0.38). On multivariate analysis, factors predictive of OS included age, extent of surgery, stage, and number of lymph nodes examined. Conclusions This study reports treatment results of a large cohort of patients who were diagnosed with malignant thymoma. This study demonstrates that the use of RT following resection for thymoma significantly improves OS for those with regional disease and marginally improves CSS.

Purpose To determine whether periprostatic treatment margins correlate with biochemical control in prostate brachytherapy patients with optimized intraprostatic dosimetry. Methods and Materials Nineteen biochemically failed brachytherapy patients were matched to 74 dosimetric and clinically equivalent nonfailures. The median followup time for the entire study population was 9.4 years. Eligibility requirements included a Day 0 intraprostatic D 90 of 100% or greater and V 100 of 90% or greater, absence of androgen deprivation therapy, and no evidence of distant metastasis in biochemically failed patients. A 5-mm annulus was constructed around the perimeter of each prostate. D 90 and V 100 at the anterior, posterior, superior, inferior, right lateral, and left lateral aspects of the annulus were evaluated for patients with biochemically controlled and failed disease. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen level of 0.40 ng/mL or less after nadir. D 90 and V 100 parameters were compared between the controlled and failed groups using logistic regression. Predictors of biochemical failure were identified using Cox regression. Results No statistically significant differences in prostate-specific antigen level, Gleason score, percent positive biopsies, or intraprostatic dosimetry were observed between the controlled and failed patients. The D 90 and V 100 at the anterior, posterior, superior, inferior, right lateral, and left lateral aspects of the annulus were not statistically different between biochemically controlled and failed groups. Conclusion In this study, there was no relationship observed between annular dosimetry and biochemical control. It is unlikely that further radial dose intensification would have altered treatment outcome in this population of patients with optimized intraprostatic dosimetry.

Study Type – Prognosis (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Cardiovascular disease is a leading cause of death in prostate cancer patients. Pretreatment ED is a surrogate for vascular pathology. Aggressive treatment of medical co-morbidity in prostate cancer patients may positively impact overall survival. OBJECTIVE • To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy. PATIENTS AND METHODS • In all, 1279 consecutive patients with clinically localized prostate cancer and pre-implant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) underwent brachytherapy. • Potency was defined as an IIEF-6 score of ≥13 without pharmacological or mechanical support. • Patients were stratified into IIEF-6-score cohorts (≤12, 13–23 and 24–30). • The median follow-up was 5.0 years. RESULTS • The 8-year overall survival (OS) of the study population was 85.1%. • The 8-year OS for IIEF-6scores ≤12, 13–23 and 24–30 were 78.0%, 92.8% and 91.4%, respectively (P

Background Obesity has correlated with adverse pathologic features on prostate biopsy and may predispose to a higher rate of prostate cancer-related death after radical prostatectomy. In this study, we examine the potential relationship between body mass index (BMI) and histopathologic findings on transperineal template-guided mapping biopsy of the prostate (TTMB). Methods From January 2005 to January 2008, 244 consecutive patients underwent TTMB using an anatomic-based technique. The criteria for TTMB included previously negative transrectal ultrasound (TRUS) biopsy with persistently elevated PSA and/or diagnosis of ASAP, or HG-PIN. The study population was divided into 4 different BMI cohorts (BMI 2 ). Biopsy findings were compared between the various BMI cohorts using one-way analysis of variance (ANOVA) and the χ 2 test. Results Pre-TTMB clinical parameters, including PSA and prostate volume, were not significantly different between the various BMI cohorts. On average, the study population had undergone 1.7 TRUS biopsies before TTMB. Of the 244 study patients, 112 (45.9%), were diagnosed with prostate adenocarcinoma on TTMB. There was no difference in the rate of cancer detection between the different BMI cohorts. Among patients diagnosed with prostate cancer, BMI did not correlate with Gleason score or percent of positive biopsy cores. When the geography of biopsy-positive cores was analyzed, there were no statistically significant differences in cancer location among the different BMI groups. Conclusions In this study, obesity did not predispose toward higher Gleason score, larger cancer volume, or geographic cancer distribution on repeat biopsy with TTMB.

Standard prostate biopsy schemes underestimate Gleason score in a significant percentage of cases. Extended biopsy improves diagnostic accuracy and provides more reliable prognostic information. In this study, we tested the hypothesis that greater biopsy core number should result in improved treatment outcome through better tailoring of therapy.From April 1995 to May 2006, 1,613 prostate cancer patients were treated with permanent brachytherapy. Patients were divided into five groups stratified by the number of prostate biopsy cores (≤6, 7-9, 10-12, 13-20, and20 cores). Biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were evaluated as a function of core number.The median patient age was 66 years, and the median preimplant prostate-specific antigen was 6.5 ng/mL. The overall 10-year bPFS, CSS, and OS were 95.6%, 98.3%, and 78.6%, respectively. When bPFS was analyzed as a function of core number, the 10-year bPFS for patients with20, 13-20, 10-12, 7-9 and ≤6 cores was 100%, 100%, 98.3%, 95.8%, and 93.0% (p0.001), respectively. When evaluated by treatment era (1995-2000 vs. 2001-2006), the number of biopsy cores remained a statistically significant predictor of bPFS. On multivariate analysis, the number of biopsy cores was predictive of bPFS but did not predict for CSS or OS.Greater biopsy core number was associated with a statistically significant improvement in bPFS. Comprehensive regional sampling of the prostate may enhance diagnostic accuracy compared to a standard biopsy scheme, resulting in better tailoring of therapy.

Objective To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS) and overall survival (OS) in high-risk prostate cancer brachytherapy patients. Patients and methods From April 1995 to June 2005, 284 patients with high-risk prostate cancer (Gleason score ≥ 8 or prostate-specific antigen > 20 ng/mL or clinical stage ≥ T2 c) underwent brachytherapy. Supplemental external beam radiation therapy was given to 257 (90.5%) patients and 179 (63.0%) received androgen deprivation therapy (ADT). Median follow up was 7.8 years. The median post-implant day 0 D90 was 118.9% of prescription dose. Patients with metastatic prostate cancer or castrate-resistant disease without obvious metastases who died of any cause were classified as dead from prostate cancer. Multiple parameters were evaluated for impact on survival. Results Twelve-year CSS, bPFS and OS were 94.2%, 89.0% and 69.7%. On multivariate analysis, bPFS was best predicted by percent positive biopsies and ADT. The analysis failed to identify any predictors for CSS, while OS was highly correlated with patient age, percent positive biopsies and diabetes. Fourteen percent of patients died from diseases of the heart, while 8%, 8% and 6% of patients died from non-prostate cancer, other causes and prostate cancer, respectively. When OS was stratified by patients with 0-3 vs ≥ 4 comorbidities, the 12-year OS was 73.0% and 52.7% (P = 0.036). Conclusions High-quality brachytherapy results in favourable bPFS and CSS for high-risk patients. Death from diseases of the heart is more than twice as likely as death from prostate cancer. Strategies to improve cardiovascular health may positively impact OS.

Purpose Our goal was to determine the correlations between dynamic contrast-enhanced MRI (DCE-MRI) kinetics of breast cancers and axillary nodal status (ANS) which may have prognostic value in designing radiation therapy recommendations. Methods and Materials A retrospective review identified 167 consecutive patients treated with external beam radiotherapy for invasive breast cancer from Jan 1, 2006 to Nov 1, 2007. Patients with DCE-MRI kinetic data from our institution who underwent axillary surgical staging prior to chemotherapy were included. ANS was assessed as positive or negative by pathology record review. For each primary cancer, maximum tumor diameter and kinetic values for initial peak enhancement (PE), percent initial rapid enhancement (RE), and percent delayed washout enhancement (WE) were measured with a computer-aided evaluation program. Univariate, multivariate, and receiver operating characteristic curve analyses were performed according to the ANS. Results Forty-six patients met study criteria, with 32 (70%) node-negative and 14 (30%) node-positive patients. Median PE was significantly greater in node-positive patients (209%) than in node-negative patients (138%, p = 0.0027). Similarly, median RE was significantly greater in node-positive patients (57%) than in node-negative patients (27%, p = 0.0436). WE was not different between groups ( p = 0.9524). Median maximum tumor diameter was greater in node-positive patients (26 mm) than in node-negative patients (15 mm, p = 0.015). Multivariate analysis showed that only PE trended toward significance ( p = 0.18). Conclusions DCE-MRI kinetics of primary breast cancers correlate with ANS. Multivariate analysis demonstrates the correlation is not due simply to underlying lesion size. If validated prospectively, DCE-MRI kinetics may aid as a tool in selecting patients or designing fields for radiation therapy.

Objectives To evaluate the effect of prostate-specific antigen (PSA) velocity (PSAV) on prostate cancer diagnosis, Gleason score, tumor location, and cancer volume in men undergoing transperineal template-guided mapping biopsy (TTMB). PSAV has been associated with greater Gleason scores and greater prostate cancer-specific mortality. Methods From January 2005 through September 2007, 217 patients underwent TTMB. The inclusion criteria included a persistently elevated PSA level and/or diagnosis of atypical small acinar proliferation or high-grade prostatic intraepithelial neoplasia on previous biopsy. The prostate gland was arbitrarily divided into 24 regions, and a median of 58 cores were obtained per patient. The patients were divided into 3 velocity cohorts according to the following changes in PSA level in the year before biopsy: ≤0.0, 0.1-1.9, and ≥2.0 ng/mL. The PSAV was evaluated as a predictor for prostate cancer diagnosis, Gleason score, tumor volume, and cancer location. Results The mean patient age was 64.2 years, with a mean prebiopsy PSA level of 8.5 ng/mL. Prostate cancer was diagnosed in 97 patients (44.7%). The study population had undergone an average of 1.8 ± 1.0 biopsies before TTMB. PSAV did not predict for prostate cancer diagnosis ( P = .84), Gleason score ( P = .78), the percentage of positive cores ( P = .37), or tumor location. Conclusions Among patients with persistently elevated PSA levels despite previously negative biopsy findings, PSAV did not reliably predict for a diagnosis of prostate cancer nor did it correlate with prostate cancer grade, volume, or location using TTMB.

Purpose: Toevaluatethe primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. Methods and Materials: From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression‐free, and overall survival. Results: The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and highrisk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. Conclusions: Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily resulted from an excess of cardiovascular deaths. Changes in lifestyle to improve cardiovascular health may improve overall survival in patients with clinically localized prostate cancer. 2008 Elsevier Inc. Prostate cancer, Primary causes of death, Brachytherapy, ADT.

Purpose To examine the efficacy of fast neutron radiotherapy in the treatment of locally advanced adenoid cystic carcinoma (ACC) of the trachea and to compare outcomes with and without high-dose-rate (HDR) endobronchial brachytherapy boost. Methods and Materials Between 1989 and 2005, a total of 20 patients with ACC of the trachea were treated with fast neutron radiotherapy at the University of Washington. Of these 20 patients, 19 were treated with curative intent. Neutron doses ranged from 10.7 to 19.95 Gy (median, 19.2 Gy). Six of these patients received an endobronchial brachytherapy boost using an HDR 192 Ir source (3.5 Gy × 2 fractions). Median duration of follow-up was 46 months (range, 10–121 months). Results The 5-year actuarial overall survival rate and median overall survival for the entire cohort were 89.4%, and 97 months, respectively. Overall survival was not statistically different among those patients receiving an endobronchial boost compared with those receiving neutron radiotherapy alone (100% vs. 68%, p = 0.36). The 5-year actuarial locoregional control rate for the entire cohort was 54.1%. The locoregional control rate was not statistically different among patients who received an endobronchial boost compared with those who received neutron radiotherapy alone (40% vs. 58%, p = 0.94). There were no cases of Grade ≥3 acute toxicity. There were 2 cases of Grade 3/4 chronic toxicity. Conclusions Fast neutron radiotherapy is an effective treatment for locally advanced adenoid cystic carcinoma of the trachea, with acceptable treatment-related toxicity.

Purpose Acute prostate brachytherapy-related morbidity is dominated by urinary symptomatology. In this study, we evaluated the effect of severe early brachytherapy-related urinary morbidity on late urinary function. Methods and materials From January 1998 to September 2003, 1029 patients were implanted for clinical stage T1b–T3a (2002 American Joint Committee on Cancer [AJCC] criteria) prostate cancer. Five hundred sixteen (50.1%) received supplemental external beam radiation therapy and 440 (42.8%) received androgen deprivation therapy. Severe acute urinary morbidity (SAUM) was defined as a dysuria frequency score of at least 4 (of 5), a dysuria severity score of at least 8 (of 10), an internation prostate symptom score (IPSS) elevated to at least 30 or 15 above preimplant value for 4 weeks, and/or requirement of a urinary catheter for at least 5 days. Dysuria severity and frequency resolution were defined as a return to within one point of baseline. IPSS resolution was defined as a return to within two points of baseline. Results Of the 1029 patients, 175 met at least one of the criteria for inclusion. Dysuria frequency resolved in 5.0 vs. 1.3 weeks and dysuria severity in 5.7 vs. 1.4 weeks, for patients with and without SAUM. The mean time for IPSS resolution was 13.8 vs. 6.6 weeks, for patients with and without SAUM. The incidence of transurethral resection (2.3% [4/173] vs. 1.5% [13/841]) and bulbomembranous urethral strictures (2.2% [4/175] vs. 1.8% [15/854]) were comparable among patients with and without SAUM. Conclusions Patients experiencing brachytherapy-related SAUM have long-term urinary function and complications comparable to patients who did not develop SAUM.

Purpose To determine whether a previously reported substratification system can be extrapolated to patients with high-risk prostate cancer treated with permanent interstitial brachytherapy. Methods and Materials Four hundred six National Comprehensive Cancer Network patients with high-risk prostate cancer treated with permanent prostate brachytherapy with or without supplemental external beam radiotherapy were stratified into good (prostate-specific antigen >20 or Gleason score ≥8 or ≥T3), intermediate (prostate-specific antigen >20 and ≥T3), and poor (Gleason score ≥8 with ≥1 additional high-risk feature) prognostic cohorts. Because of only 1 patient with intermediate high-risk disease, the analysis was performed on patients in the good and poor cohorts. Biochemical failure (BF), prostate cancer–specific mortality (PCSM), distant metastasis, and overall mortality were assessed as function of prognostic group. Multiple parameters were evaluated for impact on outcome. Results With a median followup time of 7.9 years, 10- and 14-year rates of BF and PCSM for the entire cohort were 7.8% and 3.7%, respectively. The BF rate was significantly greater in the poor prognostic category (16.8% vs. 7.8%, p = 0.041). The poor prognostic category was the strongest predictor of BF in univariate and multivariate analyses. No statistically significant differences in PCSM, distant metastasis, or overall mortality were identified between the good and poor prognostic categories. Conclusions Patients with high-risk prostate cancer treated with a brachytherapy approach have excellent long-term biochemical control and cancer-specific survival. The poor prognostic high-risk category had a higher rate of BF compared with the good prognostic category without a higher rate of PCSM or distant metastasis.

To quantify the effect of metal hip prosthesis on the ability to track and localize electromagnetic transponders.Three Calypso Beacon (Varian Medical Systems, Palo Alto, CA) transponders were implanted into 2 prostate phantoms. The geometric center of the transponders were identified on computed tomography and set as the isocenter. With the phantom stationary on the treatment table and the tracking array 14-cm above the isocenter, data were acquired by the Calypso system at 10 Hz to establish the uncertainty in measurements. Transponder positional data were acquired with unilateral hip prostheses of different metallic compositions and then with bilateral hips placed at variable separation from the phantom.Regardless of hip prosthesis composition, the average vector displacement in the presence of a unilateral prosthesis was0.5 mm. The greatest contribution to overall vector displacement occurred in the lateral dimension. With bilateral hip prosthesis, the average vector displacement was 0.3 mm. The displacement in the lateral dimension was markedly reduced compared with a unilateral hip, suggesting that there was a countervailing effect with bilateral hip prosthesis. The greatest average vector displacement was 0.6 mm and occurred when bilateral hip prostheses were placed within 4 cm of the detector array.Unilateral and bilateral hip prostheses did not have any meaningful effect on the ability to accurately track electromagnetic transponders implanted in a prostate phantom. At clinically realistic distances between the hip and detection array, the average tracking error is negligible.

OBJECTIVES To evaluate the utility of transperineal template-guided mapping biopsy (TTMB) of the prostate as an initial means of establishing tissue diagnosis. MATERIALS AND METHODS A total of 191 consecutive patients underwent TTMB of the prostate using an anatomic-based technique with sampling of 24 regions. All patients had elevated prostate-specific antigen on routine screening which was followed by a confirmatory prostate-specific antigen and none had undergone previous biopsy of the prostate. The locations of cancer involvement were recorded for each patient in an effort to approximate the percentage of men whose cancer would have been missed or Gleason score underestimated on a standard 12-core biopsy. The median number of submitted biopsy cores was 54.0. RESULTS Of the 191 study patients, 140 (73.3%) were diagnosed with cancer on TTMB. Among these biopsy-positive patients, 124 (88.6%) had clinically significant cancer. Eighty-nine of the biopsy-positive patients (64.6%) had a Gleason score of ≥7. A total of 34 of the 140 diagnosed cancers were identified exclusively in regions that fell outside of the theoretical 12-core biopsy scheme, suggesting that 24.3% of these cancers would have gone undiagnosed in the absence of TTMB. Among the 107 cancers that would have been diagnosed using a 12-core biopsy approach, 18 (16.8%) were upgraded to a Gleason score of ≥7 with mapping biopsy. CONCLUSIONS TTMB appears to provide more detailed information about prostate cancer grade and location compared with standard 12-core biopsy scheme. This information may serve as a baseline reference for image-guided biopsy (ie, magnetic resonance imaging) regimens, may facilitate clinical decision making and aid in the appropriate selection of patients for active surveillance.

Total body irradiation (TBI) is a specialized radiotherapy technique. It is frequently used as a component of treatment plans involving hematopoietic stem cell transplant for a variety of disorders, most commonly hematologic malignancies. A variety of treatment delivery techniques, doses, and fractionation schemes can be utilized. A collaborative effort of the American College of Radiology and American Society for Radiation Oncology has produced a practice guideline for delivery of TBI. The guideline defines the qualifications and responsibilities of the involved personnel, including the radiation oncologist, physicist, dosimetrist, and radiation therapist. Review of the typical indications for TBI is presented, and the importance of integrating TBI into the multimodality treatment plan is discussed. Procedures and special considerations related to the simulation, treatment planning, treatment delivery, and quality assurance for patients treated with TBI are reviewed. This practice guideline can be part of ensuring quality and safety in a successful TBI program.

Patients with clinically insignificant prostate cancer are candidates for active surveillance. However, uncertainty regarding the true extent of disease limits enthusiasm. In this study, we report our initial findings in patients with transrectal ultrasound (TRUS)-detected clinically insignificant prostate cancer undergoing transperineal template-guided mapping biopsy (TTMB) as a staging procedure.Sixty-four patients who met the Epstein criteria for clinically insignificant prostate cancer underwent TTMB. Each biopsy core position was recorded in 3 dimensions with documentation of location of each positive biopsy core, Gleason score, percentage of involvement of each core, and presence/absence of perineural invasion.Mean pre-TRUS prostate specific antigen was 4.7 ng/mL with a Gleason score of 6 involving a median of 5% of 1 TRUS core. The mean number of TTMB biopsy cores was 58.5, with 6.6 cores positive for malignancy. Ten patients had clinically insignificant prostate cancer (15.7%), 8 had no TTMB-detected cancer (12.5%), and 46 (71.9%) had clinically significant cancer. Of patients with cancer, 37 (66.1%) had bilobar involvement and 25 (44.6%) harbored a Gleason score of ≥7. In a multivariate analysis, tobacco consumption was found to be most closely related to clinically significant disease on TTMB.TRUS biopsy underestimates disease extent and Gleason score in some patients. TTMB provides a more accurate assessment of the presence of aggressive histology.

To evaluate the relationship between pre-treatment erectile function and all-cause mortality in patients with prostate cancer treated with brachytherapy.In all, 1279 consecutive patients with clinically localized prostate cancer and pre-implant erectile function assessed by the International Index of Erectile Function-6 (IIEF-6) underwent brachytherapy. Potency was defined as an IIEF-6 score of ≥13 without pharmacological or mechanical support. Patients were stratified into IIEF-6-score cohorts (≤12, 13-23 and 24-30). The median follow-up was 5.0 years.The 8-year overall survival (OS) of the study population was 85.1%. The 8-year OS for IIEF-6scores ≤12, 13-23 and 24-30 were 78.0%, 92.8% and 91.4%, respectively (P0.001). Cardiovascular events accounted for a significant portion of deaths in each IIEF-6 group. When combined with other risk factors for cardiovascular disease, an IIEF-6 score of ≤12 had an additive effect on all-cause mortality (IIEF-6 score of ≤12 and less than two comorbidities vs two or more comorbidities were 18.2% and 32.1%).A pre-implant IIEF-6score of ≤12 was associated with a higher incidence of all-cause mortality. Pre-treatment erectile dysfunction is a surrogate for underlying vascular pathology, probably explaining the lower OS in this subset of patients. Aggressive treatment of medical co-morbidity is warranted to impactOS.

Objectives To report the incidence of transition zone (TZ) cancer in patients undergoing transperineal template-guided mapping biopsy (TTMB) of the prostate gland. Methods Five hundred thirty-nine consecutive patients underwent TTMB by means of an anatomic technique with sampling of 24 defined prostate regions. The position of each biopsy core was recorded in 3 dimensions. For every patient, the location of each positive biopsy core, the number of positive cores, the Gleason score, the percentage involvement of each core, and the presence/absence of perineural invasion was documented. Results The median volumetric prostate volume was 56.0 cm3 with an ellipsoid TZ volume of 20.1 cm3. The median number of TTMB cores was 58 with a median of 11 TZ cores. Two hundred eighty-seven (53.2%) were diagnosed with prostate cancer. TZ cancer was detected in 130 (45.3%) of patients with prostate cancer but only 6 (4.6%) were confined to the TZ. Overall, 38.9% of TZ cores were positive for malignancy. Of the TZ cancers, 37 (28.5%), 64 (49.2%), and 29 (22.3%) were assigned Gleason scores 6, 7, and 8-10. Compared with a standard 12-core biopsy approach, the results of the TZ biopsy upgraded the Gleason score in 24.6% of patients. Only 4 cancers (3.1%) involving the TZ were classified as clinically insignificant. Conclusions Although only 4.6% of cancers were confined to the TZ, 45.3% of all prostate cancer patients had TZ involvement.

Transperineal permanent prostate brachytherapy is a safe and efficacious treatment option for patients with organ-confined prostate cancer. Careful adherence to established brachytherapy standards has been shown to improve the likelihood of procedural success and reduce the incidence of treatment-related morbidity. A collaborative effort of the American College of Radiology (ACR) and American Society for Therapeutic Radiation Oncology (ASTRO) has produced a practice guideline for permanent prostate brachytherapy. The guideline defines the qualifications and responsibilities of all the involved personnel, including the radiation oncologist, physicist and dosimetrist. Factors with respect to patient selection and appropriate use of supplemental treatment modalities such as external beam radiation and androgen suppression therapy are discussed. Logistics with respect to the brachtherapy implant procedure, the importance of dosimetric parameters, and attention to radiation safety procedures and documentation are presented. Adherence to these practice guidelines can be part of ensuring quality and safety in a successful prostate brachytherapy program.

Purpose To evaluate intrafraction prostate displacement among patients immobilized in the prone position using real-time monitoring of implanted radiofrequency transponders. Methods and Materials The Calypso localization system was used to track prostate motion in patients receiving external beam radiation therapy (XRT) for prostate cancer. All patients were treated in the prone position and immobilized with a thermoplastic immobilization device. Real-time measurement of prostate displacement was recorded for each treatment fraction. These measurements were used to determine the duration and magnitude of displacement along the three directional axes. Results The calculated centroid of the implanted transponders was offset from the treatment isocenter by ≥2 mm, ≥3 mm, and ≥4 mm for 38.0%, 13.9%, and 4.5% of the time. In the lateral dimension, the centroid was offset from the treatment isocenter by ≥2 mm, ≥3 mm, and ≥4 mm for 2.7%, 0.4%, and 0.06% of the time. In the superior–inferior dimension, the centroid was offset from the treatment isocenter by ≥2 mm, ≥3 mm, and ≥4 mm for 16.1%, 4.7%, and 1.5% of the time, respectively. In the anterior–posterior dimension, the centroid was offset from the treatment isocenter by ≥2 mm, ≥3 mm, and ≥4 mm for 13.4%, 3.0%, and 0.5% of the time. Conclusions Intrafraction prostate displacement in the prone position is comparable to that in the supine position. For patients with large girth, in whom the supine position may preclude accurate detection of implanted radiofrequency transponders, treatment in the prone position is a suitable alternative.

Purpose To compare biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) rates among high-risk prostate cancer patients treated with brachytherapy and supplemental external beam radiation (EBRT) using either a mini-pelvis (MP) or a whole-pelvis (WP) field. Methods and Materials From May 1995 to October 2005, 186 high-risk prostate cancer patients were treated with brachytherapy and EBRT with or without androgen-deprivation therapy (ADT). High-risk prostate cancer was defined as a Gleason score of ≥8 and/or a prostate-specific antigen (PSA) concentration of ≥20 ng/ml. Results With a median follow-up of 6.7 years, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 91.7% vs. 84.4% ( p = 0.126), 95.5% vs. 92.6% ( p = 0.515), and 79.5% vs. 67.1% ( p = 0.721), respectively. Among those patients who received ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 93.6% vs. 90.1% ( p = 0.413), 94.2% vs. 96.0% ( p = 0.927), and 73.7% vs. 70.2% ( p = 0.030), respectively. Among those patients who did not receive ADT, the 10-year bPFS, CSS, and OS rates for the WP vs. the MP arms were 82.4% vs. 75.0% ( p = 0.639), 100% vs. 88% ( p = 0.198), and 87.5% vs. 58.8% ( p = 0.030), respectively. Based on multivariate analysis, none of the evaluated parameters predicted for CSS, while bPFS was best predicted by ADT and percent positive biopsy results. OS was best predicted by age and percent positive biopsy results. Conclusions For high-risk prostate cancer patients receiving brachytherapy, there is a nonsignificant trend toward improved bPFS, CSS, and OS rates when brachytherapy is given with WPRT. This trend is most apparent among ADT-naive patients, for whom a significant improvement in OS was observed.

High-risk prostate cancer represents a therapeutic challenge for both the urologist and radiation oncologist. Biochemical outcomes with radical prostatectomy and external-beam radiation therapy are poor in this subset of patients. These unfavorable results have led some to believe that high-risk prostate cancer is not curable with conventional treatment approaches, which has been an impetus for many of the current trials using neoadjuvant chemotherapy and prostatectomy. With the established efficacy of interstitial brachytherapy, these efforts are likely excessive. Most modern trials indicate excellent biochemical control rates among high-risk patients treated with an aggressive locoregional approach that includes brachytherapy. A thoughtful review of the literature would suggest that interstitial brachytherapy offers a therapeutic advantage over other local treatment modalities and should be considered standard treatment for aggressive organ-confined prostate cancer.

OBJECTIVE: To determine whether treatment gap between supplemental beam radiation and brachytherapy implant affects rectal morbidity and likelihood of cure in the treatment of intermediate-risk prostate cancer. MATERIALS AND METHODS: Five hundred sixty-eight patients with AJCC clinical stage T1c-T2a prostate cancer, Gleason score 7 to 9 and/or prostate-specific antigen (PSA) 10 to 20 ng/mL, were randomized to implantation with Pd-103 (90 vs. 115 Gy) with 44 Gy versus 20 Gy preimplant supplemental beam radiation, respectively. Treatment-related morbidity was monitored by mailed questionnaires, using a modified Radiation Therapy Oncology Group rectal morbidity criteria at 1, 3, 6, 12, 18, and 24 months. Patients who reported grade 1 or worse rectal morbidity were interviewed by telephone to clarify details regarding their rectal bleeding. RESULTS: Persistent rectal bleeding occurred in 36 of the 548 evaluable patients (7%). The mean gap among rectal bleeders was 3.8 days and among nonbleeders was 4.8 days (P = 0.236). Higher R100 and external beam dose of 44 Gy were significant predictors of rectal bleeding on univariate and multivariate analysis. Log-rank analysis did not demonstrate any improvement in biochemical failure free survival (BFFS) with shorter gap interval. On univariate analysis, Gleason score >7, PSA >10, D90

Objectives After prostate brachytherapy, pronounced urinary irritative symptomatology occurs in a substantial minority of patients. In this study, we evaluated the impact of trospium chloride in prostate brachytherapy patients with symptoms consistent with an overactive bladder (OAB). Methods From January 1999 through December 2005, 69 permanent prostate brachytherapy patients were identified who received trospium as first-line treatment for OAB. The median interval from implant to initiation of trospium was 23.4 months. Before trospium, we obtained a postvoid residual urine assessment (PVR) and International Prostate Symptom Score (IPSS) for all patients. IPSS resolution was defined as a return to within 2 points of the pre-brachytherapy value and individual IPSS question resolution was defined by a decrease of at least 1 point. Results The mean patient age was 66.0 years, with a pre-brachytherapy prostate volume of 31.0 cm 3 and a mean preimplant IPSS of 6.5. At trospium initiation, the mean IPSS was 9.6 with a mean PVR of 12.3 mL. IPSS normalization was documented in 55 (79.7%) patients. Twelve months after trospium initiation, the IPSS had decreased by a mean of 4.3 points with the improvement most pronounced for urgency. After trospium, no clinically significant differences were noted in the mean PVR. Twenty-two patients discontinued trospium as a result of the absence of a clinical response or pharmacologic side effects, or after complete resolution of symptoms. Conclusions Nearly 80% of patients with brachytherapy-related detrusor overactivity responded favorably to trospium with improvements in IPSS (especially urgency). This was accomplished with an acceptable morbidity profile.

On univariate analysis, BF was associated (p! 0.05) with Gleason 7 and pre-tx PSA; CF with HDR boost, T stage, and pre-tx PSA; and decreased OS with IGRT, age, and Gleason 7. Race, perineural invasion (PNI) and androgen deprivation were not associated with any outcome. Higher PSA nadir (p! 0.001) and PSA nadir at 1 year (p#0.02) were associated with worse BF, CF and OS. On multivariate analysis (MVA), BF was associated (p! 0.05) with Gleason 7 and pre-tx PSA, and a trend for PNI (p 5 0.06); CF with Gleason 7, and pre-tx PSA; and worse OS with Gleason 7 and age, and trend for pre-tx PSA (p 5 0.08). PSA nadir at 1 year greater than 1 ng/mL was associated with worse outcomes when added to all three models (p#0.02). Conclusions: Dose escalated IGRT and HDR boost both yield excellent clinical outcomes. The higher rate CF for HDR boost is likely due to worse pathologic characteristics, while the increased OS is likely due to younger age. When accounted for in the MVA, treatment type was not significant.

volumes and dimensional parameters were normalized on the respective parameters of the HRCTV delineated on MRI at the time of BT (HRCTVREF). All patients were analyzed with respect to stage and the IB2 and advanced cases were also analyzed in respect to tumor response to EBRT (10 out of 16 had a reductionO50% of the initial volume) and pre-BT tumor dimension (5 patients out of 16 had a tumor widthO5 cm at the time of BT). Results:The respectivemedian volumes were 53.5 21cc (HRCTV1), 38.5 18cc (HRCTV2), 34.15 15.5cc (HRCTV3) and 35.3 19.2cc (HRCTVREF). The normalized median value was 1.5 0.57 (HRCTV1), 1.1 0.36 (HRCTV2) and 1 0.19 (HRCTV3). Median widths were 5.46 1.23cm (HRCTV1), 4.93 1.09cm (HRCTV2), 4.84 0.83cm (HRCTV3) and 4,96 0,96cm (HRCTVREF), with a normalized median width value of 1.18 0.17 (HRCTV1), 1.1 0.13 (HRCTV2) and 1.03 0.08 (HRCTV1), respectively. Median heights were 4.7 0.8cm (HRCTV1), 3.7 0.82cm (HRCTV2), 3.25 0.84cm (HRCTV3) and 3.45 1cm (HRCTV4). The normalized height values were 1.17 0.25 (HRCTV1), 1.04 0.16 (HRCTV2) and 0.94 0.08 (HRCTV3). No significant differences were found in respective HR-CTVs thickness. Subgroup analysis results according tumor stage, response to EBRT and pre-BT tumor size is reported in Fig. 1.