Active surveillance outcomes in prostate cancer patients: the use of transperineal template-guided mapping biopsy for patient selection.

PURPOSE: To evaluate active surveillance (AS) outcomes including overall survival (OS), freedom from distant metastases (FDM), freedom from therapeutic intervention (FTI), and quality of life (QOL) outcomes in prostate cancer patients using transperineal template-guided mapping biopsy (TTMB) for patient selection. METHODS: From April 2005-January 2016, 226 consecutive, prospectively evaluated prostate cancer patients underwent TTMB for either low-grade prostate cancer or persistently elevated prostate-specific antigen (PSA) and/or the presence of ASAP. Evaluated outcomes included OS, FDM, FTI and QOL including urinary, bowel, sexual function and depression. Repeat biopsy was based on PSA kinetics and/or abnormal digital rectal examination. RESULTS: Of the 226 patients, 212 (93.8%) were Gleason 3 + 3 and 14 (6.2%) were Gleason 3 + 4. The median follow-up was 5.0 years (range 0.8-13.0 years). The mean prostate volume was 61.3 cm3 with a mean of 59.5 TTMB cores/patient. At the time of AS enrollment, an average of 72.9 cores (TRUS + TTMB) had been obtained for each patient. At 8 years, OS, FTI and FDM were 92.5, 96.8 and 100%. Two hundred and twenty-two patients (98.2%) had a PSA doubling time of more than 3 years. No statistical changes in urinary function, bowel function or depression were noted. At 8 years, 73% of the patients maintained erectile function. CONCLUSION: Within the confines of the follow-up of this study, the use of TTMB for patient selection identifies a cohort of patients unlikely to develop biochemical or clinical progression and maintain a favorable quality of life.

Incidence, grade and distribution of prostate cancer following transperineal template-guided mapping biopsy in patients with atypical small acinar proliferation.

PURPOSE: To evaluate the role of transperineal template-guided mapping biopsy (TTMB) in patients with atypical small acinar proliferation (ASAP) diagnosed via transrectal ultrasound-guided needle biopsy (TRUS). METHODS: In total, 132 consecutive patients with TRUS-diagnosed ASAP underwent TTMB by means of an anatomic-based technique with sampling of 24 biopsy regions. For each of the 24 regions, 1-3 biopsy cores were obtained (depending on prostate size). No patient underwent pre-biopsy MRI imaging. The Gleason score, location of each positive biopsy core, the number of biopsy cores and percent involvement of each core were recorded. Anterior versus posterior cancer distribution was determined for both low- and high-grade (Gleason score ≥7) cancer. RESULTS: The mean patient age was 63.8 years with a mean PSA of 6.8 ng/mL. Of the 132 patients, 86 (65.2%) were diagnosed with prostate cancer. Of the entire cohort, 47 patients (54.7% of cancer patients and 35.6% of the entire cohort) were diagnosed with Gleason score ≥7. For both low- and high-grade cancers, the anterior gland and especially the anterior apex were the most common cancer locations. CONCLUSION: In patients with ASAP, TTMB diagnosed prostate cancer in 65.2% of patients and 35.6% of the entire cohort had high-grade prostate cancer. A predilection for anterior-based cancers, especially the anterior apex, was identified. Our study may serve as a baseline reference for MRI-guided biopsy regimens.

Incidence and pathological features of prostate cancer detected on transperineal template guided mapping biopsy after negative transrectal ultrasound guided biopsy.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Intrafraction displacement of prone versus supine prostate positioning monitored by real-time electromagnetic tracking.

Implanted radiofrequency transponders were used for real-time monitoring of the intrafraction prostate displacement between patients in the prone position and the same patients in the supine position. Thirteen patients had three transponders implanted transperineally and were treated prone with a custom-fitted thermoplastic immobilization device. After collecting data from the last fraction, patients were realigned in the supine position and the displacements of the transponders were monitored for 5-7 minutes. Fourier transforms were applied to the data from each patient to determine periodicity and its amplitude. To remove auto correlation from the stream of displacement data, the distribution of short-term and long-term velocity components were calculated from Poincaré plots of paired sequential vector displacements. The mean absolute displacement was significantly greater prone than supine in the superior-inferior (SI) plane (1.2 ± 0.6 mm vs. 0.6 ± 0.4 mm, p= 0.015), but not for the lateral or anterior-posterior (AP) planes. Displacements were least in the lateral direction. Fourier analyses showed the amplitude of respiratory oscillations was much greater for the SI and AP planes in the prone versus the supine position. Analysis of Poincaré plots confirmed greater short-term variance in the prone position, but no difference in the long-term variance. The centroid of the implanted transponders was offset from the treatment isocenter by > 5 mm for 1.9% of the time versus 0.8% of the time for supine. These results confirmed significantly greater net intrafraction prostate displacement of patients in the prone position than in the supine position, but most of the difference was due to respiration-induced motion that was most pronounced in the SI and AP directions. Because the respiratory motion remained within the action threshold and also within our 5 mm treatment planning margins, there is no compelling reason to choose one treatment position over the other.

Erectile dysfunction is predictive of all-cause mortality in patients with prostate cancer treated with permanent interstitial brachytherapy.

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 < 0.001). 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%). CONCLUSIONS: 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.

Prostate cancer death is unlikely in high-risk patients following quality permanent interstitial brachytherapy.

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.

Effect of the timing of hydrogel spacer placement on prostate and rectal dosimetry of low-dose-rate brachytherapy implants.

PURPOSE: To verify the dose sparing effect of hydrogel spacer (SpaceOAR™) on rectal dosimetry for prostate brachytherapy, and to determine whether prostate and rectal dosimetry was affected by the time gap between hydrogel spacer injection and brachytherapy dosimetry. MATERIAL AND METHODS: The 103Pd brachytherapy dosimetry of 174 consecutive intermediate- and high-risk patients injected with hydrogel was compared with a dosimetry of 174 contemporaneous patients without hydrogel injections. Of the SpaceOAR™ patients, 91 had hydrogel injected upon completion of brachytherapy implant, while the remaining 83 patients had hydrogel placed prior to external beam radiation therapy (EBRT), followed 2-10 weeks later by brachytherapy. Brachytherapy implants were either planned with the prostate undistorted by any hydrogel or planned with hydrogel in place. Dosimetry of the prostate and tissues at risk was determined from CT imaging on the day of brachytherapy implant. RESULTS: SpaceOAR™ significantly reduced mean and maximum rectal doses as well as rectal wall V50, but there was a statistically significant reduction of planning target volume (PTV) D90 to 121.1% of the prescribed dose in hydrogel patients compared to 123.3% in the non-hydrogel patients. Rectal dosimetry was similar between patients injected with hydrogel after brachytherapy and those with spacer injected prior to EBRT. However, patients who had hydrogel placed prior to EBRT had statistically significantly higher dosimetry indices of PTV and urethra relative to those with spacer placed at the completion of brachytherapy. CONCLUSIONS: There was a significant rectal dose sparing in the cohort with hydrogel spacer compared to a reference group without spacer injection. The rectal dose sparing effect was similar in the sub-group of patients injected with hydrogel prior to EBRT and the sub-group injected with hydrogel at the conclusion of brachytherapy.

The Impact of Body Mass Index on Freedom From Therapeutic Intervention and Quality of Life in Active Surveillance Prostate Cancer Patients.

OBJECTIVE: The objective of this study was to evaluate the impact of body mass index (BMI) on overall survival, freedom from distant metastases, rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. MATERIALS AND METHODS: Three hundred forty consecutive, prospectively evaluated AS patients underwent a staging transperineal template-guided mapping biopsy before AS enrollment and were stratified by BMI (<25, 25 to 29.9, 30 to 34.9, and >35 kg/m2). Evaluated outcomes included overall survival, freedom from distant metastases, TI, QOL to include urinary, bowel, sexual function and depression and serial postvoid residual urine measurements. The relationship between BMI and anterior prostate cancer distribution was evaluated. Repeat biopsy was based on prostate specific antigen kinetics, abnormal digital rectal examination and patient preference. RESULTS: Of the 340 patients, 323 (95%) were Gleason 3+3 and 17 patients (5.0%) were Gleason 3+4. The median follow-up was 5.2 years (range: 1 to 14 y). At 10 years, TI was instituted in 4.7%, 2.2%, 9.5%, and 25.0% of patients in BMI cohorts <25, 25 to 29.9, 30 to 34.9, and ≥35 (P=0.075). No patient has developed distant metastases. The median time to TI was 4.86 years. In multivariate analysis, TI was most closely predicted by prostate specific antigen density (P=0.071). At 8 years, no statistical differences in urinary function, bowel function, depression or postvoid residual were noted. However, a trend for erectile dysfunction was identified (P=0.106). CONCLUSION: At 10 years, BMI did not statistically predict for TI, geographic distribution of prostate cancer or QOL parameters.

The impact of age on prostate cancer progression and quality of life in active surveillance patients.

Objectives: To evaluate the impact of age on overall survival (OS), freedom from distant metastasis (FDM), rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. Materials and methods: Three hundred and five consecutive, prospectively evaluated AS patients who underwent a staging transperineal template-guided mapping biopsy (TTMB) prior to enrollment on AS were evaluated and stratified by age. Evaluated outcomes included OS, FDM, TI, and QOL to include urinary, bowel, sexual function, and depression. Post void residual (PVR) urine measurements were also followed. Repeat biopsy was based on PSA kinetics, abnormal digital rectal examination or patient preference. Results: Of the 305 patients, 290 (95.1%) were Gleason 3 + 3 and 15 patients (4.9%) were Gleason 3 + 4. The median follow-up was 5.5 years (range 1-14 years). At 10 years, TI was 0%, 1.0%, and 11.4% for patients ≤59, 60-69, and ≥70 years of age (P < .001). No patient has developed distant metastasis. The median time to TI was 4.71 years. No statistical differences in urinary function, bowel function, or depression were noted. Potency preservation was dependent on patient age. Conclusion: Within the confines of the follow-up of our series, younger patients were less likely to proceed to therapeutic intervention. In addition, patient age did not adversely impact QOL outcomes.

Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement.

PURPOSE: The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS: The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS: LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. CONCLUSIONS: LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.

Relationship between prostate cancer mortality and number of unfavourable risk factors in men treated with definitive brachytherapy.

OBJECTIVE: To explore whether the number of unfavourable pretreatment risk factors predicts cause-specific mortality in men treated with prostate brachytherapy. PATIENTS AND METHODS: Between April 1995 and March 2006, 739 patients were treated who had at least one of the following adverse risk factors: pretreatment prostate-specific antigen (PSA) level of >10 ng/mL, a Gleason score of > or =7, clinical stage > or =T2b, or a PSA velocity (PSAV) of >2 ng/mL/year. Supplemental external beam radiotherapy (EBRT) was delivered to 464 (62.8%) men and 301 (40.7%) received androgen deprivation therapy (ADT). Of men with more than two risk factors, 87% received EBRT and 62% received ADT. RESULTS: The biochemical progression-free survival (bPFS), cause-specific survival (CSS) and overall survival for all patients were 95.0%, 97.9% and 70.0% at 12 years. Men with three or four risk factors had a prostate cancer-specific mortality (PCSM) at 12 years of 5.3%, vs 1.7% for men with one or two risk factors (P= 0.006). When 'percentage of positive biopsy cores >50%' replaced PSAV as a risk factor, men with two or more risk factors had a PCSM of 8.9%, vs 1.0% for men with one or two risk factors (P= 0.001). There was no difference in all-cause mortality between the groups in either analysis. CONCLUSION: Multimodal brachytherapy results in high rates of bPFS and CSS, even for men with several unfavourable risk factors. Men with two or more unfavourable risk factors had a slightly greater risk of PCSM and no difference in all-cause mortality. The presence of three or four unfavourable intermediate-risk factors does not appear to clearly identify a group that requires further treatment intensification, although the percentage of positive cores might be more predictive than PSAV.

CT-PLANNED transperineal prostate BIOPSY IN patients without a rectum.

A patient at risk of harboring prostate cancer with a history of ulcerative colitis surgically managed with total colectomy (including the distal rectum and anal canal) underwent CT-planned transperineal prostate biopsy with fluoroscopic guidance. We describe the planning and intraoperative technique to obtain prostate biopsy cores.

The ABS brachytherapy schools.

The American Brachytherapy Society brachytherapy schools have been pivotal in teaching and evolving the art of brachytherapy over the past decades. Founded in 1995, the schools have consistently provided content for the major disease sites including gynecologic, prostate, and breast with ocular, vascular, head and neck, pediatric, intraluminal, systemic, and intraoperative approaches more selectively addressed. In addition, Physics schools, either coupled with clinical schools or as stand-alone venues, have provided an essential educational component for practicing physicists, a pivotal part of the brachytherapy team. Celebrating 25 years in existence, this historical overview of the American Brachytherapy Society brachytherapy schools is a tribute to the many teachers who have shared their expertise, to the many students who have been enthusiastic and interactive participants, and the staff who have made it all possible, with the reward of perpetuating the important and timely art of brachytherapy.

A detailed radiobiological and dosimetric analysis of biochemical outcomes in a case-control study of permanent prostate brachytherapy patients.

The purpose of this study is to determine dosimetric and radiobiological predictors of biochemical control after recalculation of prostate implant dosimetry using updated AAPM Task Group 43 (TG-43) parameters and the radiobiological parameters recommended by TG-137. All biochemical failures among patients implanted with 125I Or 103Pd sources between 1994 and March 2006 were matched 2:1 with nonfailure controls. The individual matching was by risk group, radionuclide, prescribed dose, and time of implant (one match before and one after the failed patient) resulting in a median follow-up of 10.9 years. Complete dose volume histogram (DVH) data were recalculated for all 55 cases and 110 controls after updating the original source strength by the retrospectively determined ratios of TG-43. Differential DVH data were acquired in 179 increments of prostate volume versus percentage prescribed dose. At each incremental dose level i, the biologically equivalent dose BEDi, equivalent uniform dose EUDi, and tumor control probability TCPi were calculated from the implant dose plus any external beam delivered to the patient. Total BED, EUD, and TCP were then derived from the incremental values for comparison with single point dosimetric quality parameters and DVH-based averages. There was no significant difference between failures and controls in terms of total BED (143 vs 142 Gy), EUD (95 vs 94 Gy), or TCP (0.87 vs 0.89). Conditional logistic regression analysis factored out the matching variables and stratified the cohort into each case and its controls, but no radiobiological parameter was predictive of biochemical failure. However, there was a significant difference between radiobiological parameters of 125I and 103Pd due to less complete coverage of the target volume by the former isotope. The implant BED and TCP were highly correlated with the D90 and natural prescription doses and a series of mean DVH-based doses such as the harmonic mean and expressions of the generalized EUD. In this case-control study of prostate brachytherapy biochemical failures and nonfailures, there were no radiobiological parameters derived from detailed DVH-based analysis that predicted for biochemical control. This may indicate that in our approach, implant dosimetry is at or near the limits of clinically effective dose escalation.

AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: report of Task Group 137.

During the past decade, permanent radioactive source implantation of the prostate has become the standard of care for selected prostate cancer patients, and the techniques for implantation have evolved in many different forms. Although most implants use 125I or 103Pd sources, clinical use of 131Cs sources has also recently been introduced. These sources produce different dose distributions and irradiate the tumors at different dose rates. Ultrasound was used originally to guide the planning and implantation of sources in the tumor. More recently, CT and/or MR are used routinely in many clinics for dose evaluation and planning. Several investigators reported that the tumor volumes and target volumes delineated from ultrasound, CT, and MR can vary substantially because of the inherent differences in these imaging modalities. It has also been reported that these volumes depend critically on the time of imaging after the implant. Many clinics, in particular those using intraoperative implantation, perform imaging only on the day of the implant. Because the effects of edema caused by surgical trauma can vary from one patient to another and resolve at different rates, the timing of imaging for dosimetry evaluation can have a profound effect on the dose reported (to have been delivered), i.e., for the same implant (same dose delivered), CT at different timing can yield different doses reported. Also, many different loading patterns and margins around the tumor volumes have been used, and these may lead to variations in the dose delivered. In this report, the current literature on these issues is reviewed, and the impact of these issues on the radiobiological response is estimated. The radiobiological models for the biological equivalent dose (BED) are reviewed. Starting with the BED model for acute single doses, the models for fractionated doses, continuous low-dose-rate irradiation, and both homogeneous and inhomogeneous dose distributions, as well as tumor cure probability models, are reviewed. Based on these developments in literature, the AAPM recommends guidelines for dose prescription from a physics perspective for routine patient treatment, clinical trials, and for treatment planning software developers. The authors continue to follow the current recommendations on using D90 and V100 as the primary quantitles, with more specific guidelines on the use of the imaging modalities and the timing of the imaging. The AAPM recommends that the postimplant evaluation should be performed at the optimum time for specific radionuclides. In addition, they encourage the use of a radiobiological model with a specific set of parameters to facilitate relative comparisons of treatment plans reported by different institutions using different loading patterns or radionuclides.

Prostate cancer control and survival in Vietnam veterans exposed to Agent Orange.

BACKGROUND: In this study, we evaluated the impact of Agent Orange exposure on survival in Vietnam Veterans undergoing prostate brachytherapy. METHODS AND MATERIAL: From May 1995 to January 2005, 81 Vietnam veterans (29 with Agent Orange exposure and 52 without) and 433 nonveterans of comparable age (mean age, 58 years) underwent prostate brachytherapy. The mean follow-up was 5.0 years. Biochemical progression-free survival (bPFS) was defined as a prostate-specific antigen (PSA)< or =0.40ng/mL after nadir. Patients with metastatic prostate cancer or hormone refractory disease without obvious metastases who died of any cause were classified as died of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple parameters were evaluated for impact on survival. RESULTS: At 9 years, Agent Orange-exposed men were least likely to remain biochemically controlled (89.5%, 100%, and 97.2% in Agent Orange-exposed, nonexposed veterans, and nonveterans, respectively, p=0.012). No significant differences in cause-specific (CSS) (p=0.832) or overall survival (OS) (p=0.363) were discerned. In multivariate analysis, CSS was best predicted by Gleason Score and day 0 D(90), whereas Gleason Score, % positive biopsies, and D(90) predicted for bPFS. None of the evaluated parameters predicted for OS, however, a trend was identified for better OS in younger patients and those with a higher D(90). In addition, Agent Orange exposure did not predict for any of the survival parameters. To date, 22 patients have died (metastatic prostate cancer two, second malignancies nine, cardiovascular disease eight, trauma two, and pulmonary one). CONCLUSIONS: In this cohort of prostate brachytherapy patients, Agent Orange exposure did not statistically impact survival in multivariate analysis.

Analysis of the Pro-Qura Database: rectal dose, implant quality, and brachytherapist's experience.

PURPOSE: This study analyzed rectal dosimetry outcomes of Pro-Qura proctored implants to assess the achievability of proposed rectal dose constraints in the setting of standardized pre- and postimplant dosimetry in community-based brachytherapy programs. METHODS AND MATERIALS: From August 2005 to July 2007, 713 postimplant CT scans were evaluated from 26 brachytherapists actively participating in Pro-Qura. Postimplant dosimetry was performed in a standardized fashion. The entirety of the rectal wall was contoured and evaluated for dose. Rectal dose was defined in terms of the volume of the rectum receiving 100% of the prescription dose (R(100)). Criteria for implant adequacy for both (103)Pd and (125)I included a prostate the percentage of the prostate volume covered by the prescription dose (V(100))>80%, a prostate the maximum dose covering 90% of the prostate volume (D(90)) of 90-140%, and an R(100)<1.0cm(3) for early (Day 0-7) dosimetry and <1.3cm(3) for late (Day 20-45) dosimetry. RESULTS: Mean prostatic volume was 35.1cm(3). The mean time from implant to CT scan was 29.9 days (range, 0-45 days). The respective mean overall prostate V(100) and D(90) were 89% and 101%, respectively, and remained consistent for sequence groups 1 through 6. Overall, the mean R(100) was 0.97+/-1.04cm(3). The R(100) was 1.15cm(3) for sequence Group 1 and with each subsequent sequence group decreased with a nadir of 0.83cm(3) in sequence Group 6 (p=0.22). Rectal dosimetry was deemed inadequate in 39% of Group 1 implants but only 22% in Group 6 (p=0.016). The reduced rectal doses did not impact prostate gland coverage. CONCLUSIONS: Using standardized dosimetry, R(100) improved with increasing brachytherapist's experience, reaching a plateau after approximately 20 patients.

Clinical practice and quality assurance challenges in modern brachytherapy sources and dosimetry.

Modern brachytherapy has led to effective treatments through the establishment of broadly applicable dosimetric thresholds for maximizing survival with minimal morbidity. Proper implementation of recent dosimetric consensus statements and quality assurance procedures is necessary to maintain the established level of safety and efficacy. This review classifies issues as either "systematic" or "stochastic" in terms of their impact on large groups or individual patients, respectively. Systematic changes affecting large numbers of patients occur infrequently and include changes in source dosimetric parameters, prescribing practice, dose calculation formalism, and improvements in calculation algorithms. The physicist must be aware of how incipient changes accord with previous experience. Stochastic issues involve procedures that are applied to each patient individually. Although ample guidance for quality assurance of brachytherapy sources exists, some ambiguities remain. The latest American Association of Physicists in Medicine guidance clarifies what is meant by independent assay, changes source sampling recommendations, particularly for sources in sterile strands and sterile preassembled needles, and modifies action level thresholds. The changing environment of brachytherapy has not changed the fact that the prime responsibility for quality assurance in brachytherapy lies with the institutional medical physicist.

Prostate brachytherapy in men > or =75 years of age.

PURPOSE: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in prostate cancer patients aged > or =75 years undergoing brachytherapy with or without supplemental therapies. METHODS AND MATERIALS: Between April 1995 and August 2004, 145 consecutive patients aged > or =75 years underwent permanent prostate brachytherapy. Median follow-up was 5.8 years. Biochemical progression-free survival was defined by a prostate-specific antigen level < or =0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone-refractory disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on survival. RESULTS: Nine-year CSS, bPFS, and OS rates for the entire cohort were 99.3%, 97.1%, and 64.5%, respectively. None of the evaluated parameters predicted for CSS, whereas bPFS was most closely predicted by percentage positive biopsies. Overall survival and non-cancer deaths were best predicted by tobacco status. Thirty-seven patients have died, with 83.8% of the deaths due to cardiovascular disease (22 patients) or second malignancies (9 patients). To date, only 1 patient (0.7%) has died of metastatic prostate cancer. CONCLUSIONS: After brachytherapy, high rates of CSS and bPFS are noted in elderly prostate cancer patients. Overall, approximately 65% of patients are alive at 9 years, with survival most closely related to tobacco status. We believe our results support an aggressive locoregional approach in appropriately selected elderly patients.

Primary causes of death after permanent prostate brachytherapy.

PURPOSE: To evaluate the 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 high-risk 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.