Multi-Frequency 3D Shear Wave Absolute Vibro-Elastography (S-WAVE) System for the Prostate.

This article describes a novel system for quantitative and volumetric measurement of tissue elasticity in the prostate using simultaneous multi-frequency tissue excitation. Elasticity is computed by using a local frequency estimator to measure the three-dimensional local wavelengths of steady-state shear waves within the prostate gland. The shear wave is created using a mechanical voice coil shaker which transmits simultaneous multi-frequency vibrations transperineally. Radio frequency data is streamed directly from a BK Medical 8848 transrectal ultrasound transducer to an external computer where tissue displacement due to the excitation is measured using a speckle tracking algorithm. Bandpass sampling is used that eliminates the need for an ultra-fast frame rate to track the tissue motion and allows for accurate reconstruction at a sampling frequency that is below the Nyquist rate. A roll motor with computer control is used to rotate the transducer and obtain 3D data. Two commercially available phantoms were used to validate both the accuracy of the elasticity measurements as well as the functional feasibility of using the system for in vivo prostate imaging. The phantom measurements were compared with 3D Magnetic Resonance Elastography (MRE), where a high correlation of 96% was achieved. In addition, the system has been used in two separate clinical studies as a method for cancer identification. Qualitative and quantitative results of 11 patients from these clinical studies are presented here. Furthermore, an AUC of 0.87±0.12 was achieved for malignant vs. benign classification using a binary support vector machine classifier trained with data from the latest clinical study with leave one patient out cross-validation.

An Updated Analysis of the Survival Endpoints of ASCENDE-RT.

PURPOSE: Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P < .001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up. METHODS: Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received an 125I implant prescribed to a minimum peripheral dose of 115 Gy. Two hundred patients were randomized to the DE-EBRT arm and 198 to the LDR-PB arm. RESULTS: The 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P < .001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm. CONCLUSIONS: Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.

After ASCENDE-RT: Biochemical and survival outcomes following combined external beam radiotherapy and low-dose-rate brachytherapy for high-risk and unfavourable intermediate-risk prostate cancer, a population-based analysis.

PURPOSE: To evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB). METHODS AND MATERIALS: A population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial. RESULTS: The median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p < 0.001), 73 ± 8% (p < 0.001), and 77 ± 9% (p = 0.098) for the ineligible patients. CONCLUSIONS: In this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

Registration of trans-perineal template mapping biopsy cores to volumetric ultrasound.

PURPOSE: Pathology from trans-perineal template mapping biopsy (TTMB) can be used as labels to train prostate cancer classifiers. In this work, we propose a framework to register TTMB cores to advanced volumetric ultrasound data such as multi-parametric transrectal ultrasound (mpTRUS). METHODS: The framework has mainly two steps. First, needle trajectories are calculated with respect to the needle guiding template-considering deflections in their paths. In standard TTMB, a sparsely sampled ultrasound volume is taken prior to the procedure which contains the template overlaid on top of it. The position of this template is detected automatically, and the cores are mapped following the calculated needle trajectories. Second, the TTMB volume is aligned to the mpTRUS volume by a two-step registration method. Using the same transformations from the registration step, the cores are registered from the TTMB volume to the mpTRUS volume. RESULTS: TTMB and mpTRUS of 10 patients were available for this work. The target registration errors (TRE) of the volumes using landmarks picked by three research assistants (RA) and one radiation oncologist (RO) were on average 1.32 ± 0.7 mm and 1.03 ± 0.6 mm, respectively. Additionally, on average, our framework takes only 97 s to register the cores. CONCLUSION: Our proposed framework allows a quick way to find the spatial location of the cores with respect to volumetric ultrasound. Furthermore, knowing the correct location of the pathology will facilitate focal treatment and will aid in training imaging-based cancer classifiers.

A biochemical definition of cure after brachytherapy for prostate cancer.

BACKGROUND AND PURPOSE: To identify a PSA threshold value at an intermediate follow-up time after low dose rate (LDR) prostate brachytherapy associated with cure, defined as long-term (10-15 year) freedom from prostate cancer. MATERIALS AND METHODS: Data from 7 institutions for 14,220 patients with localized prostate cancer treated with LDR brachytherapy, either alone (8552) or with external beam radiotherapy (n = 1175), androgen deprivation (n = 3165), or both (n = 1328), were analyzed. Risk distribution was 42.4% favorable, 49.2% intermediate, and 8.4% high-risk. Patients with clinical failure before 3.5 years were excluded. Kaplan-Meier analysis was used with clinical failure (local, distant, regional or biochemical triggering salvage) as an endpoint for each of four PSA categories: PSA ≤ 0.2, >0.2 to ≤0.5, >0.5 to ≤1.0, and >1.0 ng/mL. PSA levels at 4 years (±6 months) in 8746 patients without clinical failure were correlated with disease status at 10-15 years. RESULTS: For the 77.1% of patients with 4-year PSA ≤ 0.2, the freedom-from-recurrence (FFR) rates were 98.7% (95% CI 98.3-99.0) at 10 years and 96.1% (95% CI 94.8-97.2) at 15 years. Three independent validation cohorts confirmed 97-99% 10-year FFR rates with 4-year PSA ≤ 0.2. Successive PSA categories were associated with diminished disease-free rates at 10 and 15 years. PSA category was strongly associated with treatment success (p < 0.0005). CONCLUSIONS: Since 98.7% of patients with PSA ≤ 0.2 ng/mL at 4 years after LDR prostate brachytherapy were disease-free beyond 10 years, we suggest adopting this biochemical definition of cure for patients with ≥4 years' follow-up after LDR brachytherapy.

Using a surgical prostate-specific antigen threshold of >0.2 ng/mL to define biochemical failure for intermediate- and high-risk prostate cancer patients treated with definitive radiation therapy in the ASCENDE-RT randomized control trial.

PURPOSE: To compare biochemical failure using a prostate-specific antigen (PSA) threshold of >0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL). METHODS AND MATERIALS: Androgen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of >0.2 ng/mL. RESULTS: Compared to nadir+2 ng/mL, the >0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the >0.2 ng/mL threshold (p < 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (>0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319). CONCLUSIONS: Replacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.

Brachytherapy for Intermediate-Risk Prostate Cancer, Androgen Deprivation, and the Risk of Death.

PURPOSE: To determine whether the use of 6 months' adjuvant androgen deprivation therapy (ADT) combined with brachytherapy for intermediate-risk (IR) and low-risk (LR) prostate cancer is associated with an increased risk of cardiovascular death. METHODS AND MATERIALS: This is a retrospective analysis of prospectively collected data from men treated in the British Columbia Cancer Agency brachytherapy program from 1998 to 2012. Men were categorized by risk group and ADT use. Cardiac and other comorbidities were recorded and compared between groups. Biochemical control (Phoenix definition, nadir + 2 ng/mL) was ascertained. Overall, prostate, cardiac, and other-cause mortality were analyzed by the Kaplan-Meier method and Fine and Gray competing-risk analysis. RESULTS: The study included 3155 men (1142 with LR cancer and 2013 with IR cancer) who have been followed up for a median of 7.9 years. ADT was received by 47% of IR patients and 37% of LR patients for a median of 6 months. Men with IR cancer were older and had more cardiac and other comorbidities than LR cases (P<.01). Biochemical control improved from 86% to 89% at 10 years with the use of ADT (P=.006). Overall survival was inferior in patients receiving ADT (84% vs 86% at 10 years, P=.0274), and on competing-risk analysis, cardiovascular mortality in patients receiving ADT was higher in IR cases, 5.2% versus 3.6% at 10 years (P=.0493), but not in LR cases. Multivariate analysis confirmed increased cardiac mortality in IR patients receiving ADT (hazard ratio, 1.95 [95% confidence interval, 1.15-3.34]; P=.014). CONCLUSIONS: ADT adds little meaningful benefit in terms of biochemical control for IR men treated with low-dose-rate brachytherapy but likely decreases overall survival because of increased cardiac mortality. IR patients were older and had more cardiac risk factors than LR prostate cases; this may be because of a screening effect, case selection, or common etiologic cause.

High-intermediate prostate cancer treated with low-dose-rate brachytherapy with or without androgen deprivation therapy.

PURPOSE: To describe outcomes of men with unfavorable (high-tier) intermediate risk prostate cancer (H-IR) treated with low-dose-rate (LDR) brachytherapy, with or without 6 months of androgen deprivation therapy (ADT). METHODS AND MATERIALS: Patients with H-IR prostate cancer, treated before 2012 with LDR brachytherapy without external radiation are included. Baseline tumor characteristics are described. Outcomes between groups receiving ADT are measured by Phoenix (nadir +2 ng/mL), and threshold 0.4 ng/mL biochemical relapse definitions (bNEDs), as well as clinical end points. Standard descriptive and actuarial statistics are used. RESULTS: Two hundred sixty men were eligible, 139 (53%) did not receive ADT and 121 (47%) did. Median follow-up was 5 years. Men treated with ADT had higher T stage and percent positive cores but lower pathologic grade group. bNED rates with and without ADT at 5 years are 86% and 85% (p = 0.52) with the Phoenix definition, and 83% and 78% (p = 0.13) with the threshold definition. Local recurrence or metastasis were rare in both groups (<5%, p = not significant). Death from prostate cancer only occurred in 4 patients, 2 in each group. Overall survival was 85% in those treated with ADT and 93% without at 8 years, p = 0.15. CONCLUSIONS: The addition of 6 months of ADT to LDR brachytherapy for H-IR prostate cancer does not improve 5 year prostate specific antigen control, and we no longer routinely recommended it.

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study.

PURPOSE: To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). MATERIAL AND METHODS: Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. RESULTS: Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. CONCLUSIONS: Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB.

ASCENDE-RT: An Analysis of Health-Related Quality of Life for a Randomized Trial Comparing Low-Dose-Rate Brachytherapy Boost With Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer.

PURPOSE: To report the patient-reported health-related quality of life (HR-QoL) outcomes for a multicenter randomized trial evaluating the safety and efficacy of 2 different techniques for dose escalation. METHODS AND MATERIALS: A total of 357 men with intermediate- and high-risk prostate cancer were stratified by risk group and randomized (1:1) to either a dose-escalated external beam (DE-EBRT) boost (n=177) or a low-dose-rate prostate brachytherapy (LDR-PB) boost (n=180) as part of combined modality therapy. The HR-QoL was assessed using the SF36v2 questionnaire, with additional scales for urinary, bowel, and sexual function. Date of starting androgen deprivation therapy was considered time zero, the median follow-up of 6 years. Scales were scored from 0 to 100; a decline in a mean score ≥10 compared with baseline was considered a clinically significant decline. This was an intent-to-treat analysis. RESULTS: Mean domain scores at baseline were well balanced between the 2 treatment arms. A clinically significant decline in mean scores in both the arms compared with baseline was noted for role physical (DE-EBRT [-11.4] and LDR-PB [-15.3]) and sexual function scale (DE-EBRT [-15.1] and LDR-PB [-19.2]). There was a significantly larger drop in mean scores in the LDR-PB group compared with the DE-EBRT group for physical function (-15.3 vs -6.9; P=.03), urinary function (-3.6 vs -0.5; P=.04). CONCLUSION: At 6 years' follow up, there were no significant differences in mean scores in 9 of 11 scales compared with baseline in both arms. A clinically significant decline in mean scores was noted in both arms for role physical and sexual function scales. There was a statistically significant decline in physical function and urinary function scales in the LDR-PB arm compared with the DE-EBRT arm.

ASCENDE-RT: An Analysis of Treatment-Related Morbidity for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost with a Dose-Escalated External Beam Boost for High- and Intermediate-Risk Prostate Cancer.

PURPOSE: To report the genitourinary (GU) and gastrointestinal (GI) morbidity and erectile dysfunction in a randomized trial comparing 2 methods of dose escalation for high- and intermediate-risk prostate cancer. METHODS AND MATERIALS: ASCENDE-RT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) enrolled 398 men, median age 68 years, who were then randomized to either a standard arm that included 12 months of androgen deprivation therapy and pelvic irradiation to 46 Gy followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. At clinic visits, investigators recorded GU and GI morbidity and information on urinary continence, catheter use, and erectile function. Exclusion of 15 who received nonprotocol treatment and correction of 14 crossover events left 195 men who actually received a DE-EBRT boost and 188, an LDR-PB boost. Median follow-up was 6.5 years. RESULTS: The LDR-PB boost increased the risk of needing temporary catheterization and/or requiring incontinence pads. At 5 years the cumulative incidence of grade 3 GU events was 18.4% for LDR-PB, versus 5.2% for DE-EBRT (P<.001). Compared with the cumulative incidence, the 5-year prevalence of grade 3 GU morbidity was substantially lower for both arms (8.6% vs 2.2%, P=.058). The 5-year cumulative incidence of grade 3 GI events was 8.1% for LDR-PB, versus 3.2% for DE-EBRT (P=.124). The 5-year prevalence of grade 3 GI toxicity was lower than the cumulative incidence for both arms (1.0% vs 2.2%, respectively). Among men reporting adequate baseline erections, 45% of LDR-PB patients reported similar erectile function at 5 years, versus 37% after DE-EBRT (P=.30). CONCLUSIONS: The incidence of acute and late GU morbidity was higher after LDR-PB boost, and there was a nonsignificant trend for worse GI morbidity. No differences in the frequency of erectile dysfunction were observed.

Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer.

PURPOSE: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. METHODS AND MATERIALS: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. RESULTS: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). CONCLUSIONS: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

Robustness to source displacement in dual air kerma strength planning for focal low-dose-rate brachytherapy of prostate cancer.

PURPOSE: To describe the use of dual source strength implants for focal low-dose-rate brachytherapy. METHODS AND MATERIALS: An interneedle dual source strength planning strategy is described for focal low-dose-rate brachytherapy of the prostate. The implanted treatment plans were designed using peripheral (except near the rectum) needles loaded with high strength (0.9 U) sources and central needles loaded with low strength (0.4 U) sources ("interneedle" dual strength planning). This approach has been applied for focally treating 3 patients. In this article, we compare the characteristics and robustness to source motion of interneedle dual strength planning with four alternative planning strategies (single strength high, low, and intermediate, and intraneedle dual strength) on 50 simulated cases. RESULTS: Interneedle dual source strength planning results in greater robustness to source motion and overall lower seed and needle density compared to the standard low source strength planning currently used in our centre. This planning approach is also significantly superior to single strength high, single strength intermediate and intraneedle dual strength planning strategies in terms of high dose to the urethral avoidance structure. CONCLUSIONS: The use of interneedle dual source strength treatment plans for focal low-dose-rate brachytherapy is possibly the practical solution for limiting the density of sources required to deliver the prescribed dose while limiting proximity of high strength sources to organs at risk.

Rectal Ulcers and Rectoprostatic Fistulas after (125)I Low Dose Rate Prostate Brachytherapy.

PURPOSE: Radiation induced rectal ulcers and fistulas are rare but significant complications of low dose rate prostate brachytherapy for localized prostate cancer. We describe the incidence of ulcers and fistulas, and associated risk factors. MATERIALS AND METHODS: We reviewed the records of 4,690 patients with localized prostate cancer who were treated with low dose rate (125)I prostate brachytherapy to a dose of 144 Gy with or without 6 months of androgen deprivation therapy. Patient, disease, comorbidity, treatment, dosimetric and posttreatment intervention factors were analyzed for an association with ulcer or fistula formation. RESULTS: At a median followup of 53 months 21 cases were identified, including 15 rectal ulcer cases, of which 6 progressed to fistulas, and an additional 6 cases of fistulas with no prior documented ulcers. Overall 9 rectal ulcer cases (0.19%) and 12 fistula cases (0.26%) were identified. In 8 of 15 patients ulcers healed with conservative management. No fistulas healed without surgical management. Two patients with fistulas died. Eight patients diagnosed with rectal ulcers subsequently underwent rectal biopsies, after which fistulas developed in 3. One patient with a de novo fistula underwent a preceding biopsy. Urinary interventions such as transurethral resection of the prostate were performed after brachytherapy in 5 of 12 patients with fistulas compared to 0 of 9 with ulcers alone. Argon plasma coagulation of the rectum for hematochezia was performed after brachytherapy in 3 of 12 patients with fistulas. CONCLUSIONS: Rates of post-brachytherapy rectal ulcers and fistulas are low as previously described. Post-brachytherapy interventions such as rectal biopsy, argon coagulation and urinary intervention may increase the risk of fistulas.

Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity.

PURPOSE: Rates of late toxicity are higher for salvage treatment of local recurrence after prior radiotherapy. We present our experience with salvage prostate brachytherapy (BT) for local recurrence after definitive external beam radiotherapy with attention to the relationship between dose and late toxicity. METHODS AND MATERIALS: From 2005 to 2012, 18 patients with biopsy proven locally recurrent prostate cancer and negative staging received low-dose-rate BT with a prescribed dose of 130-144 Gy. Toxicities were graded using Common Terminology Criteria for Adverse Events, version 3.0. RESULTS: Median followup is 31.5 months (range, 12-104). International Prostate Symptom Scores peaked at 3 months (median, 21/35), returning to baseline by 24 months. Urinary catheterization rate was 33% (median duration, 14 days; range, 1-90 days). Late Grade 3/4 genitourinary toxicity occurred in 1 patient each, one of whom also had Grade 3 late gastrointestinal toxicity; urethral strictures developed in three others. These 5 patients with late toxicity had higher dose to the prostate (isodose enclosing 90% [D90] median, 151 Gy; range, 135-185 Gy) compared with those without late complications (median, 134 Gy; range, 105-165; p < 0.04). Acute gastrointestinal toxicity Grade <3 occurred in 44%. Four patients (22%) experienced biochemical failure. CONCLUSION: Salvage low-dose-rate prostate BT can provide durable biochemical control. Care should be taken to select patients with higher likelihood of organ-confined disease. The goal of planning should be to treat the recurrent disease to an adequate dose with careful attention to maintain a conservative D90.

Patterns of recurrence after low-dose-rate prostate brachytherapy: a population-based study of 2223 consecutive low- and intermediate-risk patients.

OBJECTIVES: This study examined patterns of recurrence after low-dose-rate prostate brachytherapy (LDR-PB), estimated local recurrence rate and compared that rate to the estimated local recurrence rate after radical prostatectomy (RP). METHODS AND MATERIALS: A prospective database was maintained with clinical, dosimetric, and outcome data for all LDR-PB implantation procedures performed at our institution. From 1998 to 2008, 2223 patients with prostate cancer received LDR-PB without supplemental external beam radiation therapy. Patients who developed Phoenix-defined biochemical failure were reviewed for sites of relapse and investigations completed. RESULTS: At a median follow-up of 5 years, 108 of 2223 patients (4.8%) developed biochemical relapse. In 1 additional patient, local relapse was found on transurethral prostate resection, but his prostate-specific antigen concentration was well short of triggering Phoenix-defined failure. Of the 109 patients with disease relapse, 18 of 2223 (0.8%) had a proven local recurrence, and 30 of 2223 (1.3%) had a proven distant recurrence. The remaining 61 of 2223 patients (2.7%) had unidentified sites of recurrence; of these, 57 patients (93%) had digital rectal examinations (DREs), 18 (30%) had post-treatment biopsies, 45 (74%) had bone scans, and 34 (56%) had computed tomography imaging of the abdomen and pelvis. If every biochemical failure were local, the local recurrence rate would be as high as 4.9%; however, by excluding those with proven distant failure and those with both a negative DRE and biopsy, we estimate that the local recurrence rate is 2.7% or less. CONCLUSIONS: In the context of limitations of the study design, our population-based analysis indicates that the local recurrence rate after LDR-PB is as low or lower than that after RP in our jurisdiction.

Regional dose metrics as predictors of biochemical failure and local recurrence after low-dose-rate prostate brachytherapy.

PURPOSE/OBJECTIVES: To assess regional dose metrics as predictors of disease relapse after low-dose-rate prostate brachytherapy. METHODS AND MATERIALS: A cohort of 2000 consecutive patients with prostate cancer treated with iodine-125 low-dose-rate prostate brachytherapy monotherapy was implanted between July 1998 and November 2007. Within this group, 89 patients had disease relapse, 13 of whom had local failure by clinical or histopathologic criteria. Postoperative computed tomography scans were available for 96.3% of cases, resulting in a data set composed of 87 relapses (including all 13 local relapses) and 1839 nonrelapsed controls. Using the VariSeed 8.0.2 software, we divided the original prostate contours into four quadrants: anterior-superior (ASQ), posterior-superior, anterior-inferior (AIQ), and posterior-inferior. DVH-derived dosimetric parameters were calculated for the whole prostate and each quadrant. RESULTS: Gleason score, prostate-specific antigen, and the use of androgen-deprivation therapy were predictive of disease relapse in a multivariate Cox model. Whole prostate dose metrics did not predict biochemical or local relapse. Dosimetric coverage was sparsest in the ASQ. Despite low values, dose to the ASQ was not predictive of relapse, nor were doses to the remaining three quadrants. AIQ coverage was predictive of local relapse in multivariate Cox model (p = 0.042). However, the AIQ dose metrics exhibited a large variance and on bootstrap analysis, a p value of <0.05 was seen in only 51% of 1000 iterations. CONCLUSIONS: Consistent with previous reports, whole-prostate dose metrics were not predictive of disease relapse (any) or local relapse in our patients. Although significant ASQ underdosage relative to other prostate regions was observed, ASQ dose coverage did not correlate with relapse.

Incidence of second malignancies in prostate cancer patients treated with low-dose-rate brachytherapy and radical prostatectomy.

PURPOSE: To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population. METHODS AND MATERIALS: From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determine whether treatment (RP vs BT) was associated with second malignancy risk. RESULTS: The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P<.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P<.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56). CONCLUSIONS: After adjustment for covariates, BT patients did not have an increased second malignancy risk compared with RP patients. Further follow-up of this cohort is needed given the potential latency of radiation-induced malignancies.