A unified strategy to focal brachytherapy incorporating transperineal biopsy, image fusion, and real-time implantation with and without rectal spacer simulated in prostate phantoms.

Purpose: To develop an approach to the diagnosis and treatment of prostate cancer using one platform for fusion biopsy, followed by focal gland ablation utilizing permanent prostate brachytherapy with and without a rectal spacer. Material and methods: Prostate phantoms containing multiparametric magnetic resonance imaging (mpMRI) regions of interest (ROI) underwent fusion biopsy, followed by image co-registration of positive sites to a treatment planning brachytherapy program. A partial hemi-ablation and both posterior lobes using a Mick applicator and linked stranded seeds were simulated. Dummy sources were modeled as iodine-125 (125I) with a prescribed dose of at least 210 Gy to gross tumor (GTV) and clinical target volume (CTV), as defined by mpMRI visible ROI and surrounding negative biopsy sites. Computer tomograms (CT) were performed post-implant prior to and after rectal spacer insertion. Different prostate and rectal constraints were compared with and without the spacer. Results: The intra-operative focal volumes of CTV ranged from 6.2 to 14.9 cc (mean, 11.3 cc), and the ratio of focal volume/whole prostate volume ranged between 0.19 and 0.42 (mean, 0.31). The intra- and post-operative mean focal D90 of GTV, CTV, and for the entire prostate gland was 265 Gy and 235 Gy, 214 Gy and 213 Gy, and 66.1 Gy and 57 Gy, respectively. On average, 13 mm separation was achieved between the prostate and the rectum (range, 12-14 mm) on post-operative CT. The mean doses in Gy to 2 cc of the rectum (D2cc) without spacer vs. with spacer were 39.8 Gy vs. 32.6 Gy, respectively. Conclusions: Doses above 200 Gy and the implantation of seeds in clinically significant region for focal therapy in phantoms are feasible. All rectal dosimetric parameters improved for the spacer implants, as compared with the non-spacer implants. Further validation of this concept is warranted in clinical trials.

Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907).

PURPOSE: This phase 3 randomized investigation was designed to determine whether 30 months of androgen deprivation therapy (ADT) was superior to 6 months of ADT when combined with brachytherapy and external beam radiation therapy (EBRT) for localized high-risk prostate cancer. METHODS AND MATERIALS: This study was conducted at 37 hospitals on men aged 40 to 79 years, with stage T2c-3a, prostate-specific antigen >20 ng/mL, or Gleason score >7, who received 6 months of ADT combined with iodine-125 brachytherapy followed by EBRT. After stratification, patients were randomly assigned to either no further treatment (short arm) or 24 months of adjuvant ADT (long arm). According to the Phoenix definition of failure, the primary endpoint was the cumulative incidence of biochemical progression. Secondary endpoints included clinical progression, metastasis, salvage treatment, disease-specific mortality, overall survival, and grade 3+ adverse events. An intention-to-treat analysis was conducted using survival estimates determined using competing risk analyses. RESULTS: Of 332 patients, 165 and 167 were randomly assigned to the short and long arms, respectively. The median follow-up period was 9.2 years. The cumulative incidence of biochemical progression at 7 years was 9.0% (95% CI, 5.5-14.5) and 8.0% (4.7-13.5) in the short and long arms, respectively (P = .65). The outcomes of secondary endpoints did not differ significantly between the arms. Incidence rates of endocrine- and radiation-related grade 3+ adverse events for the short versus long arms were 0.6 versus 1.8% (P = .62) and 1.2 versus 0.6% (P = .62), respectively. CONCLUSIONS: Both treatment arms showed similar efficacy among selected populations with high-risk features. The toxicity of the trimodal therapy was acceptable. The present investigation, designed as a superiority trial, failed to demonstrate that 30-month ADT yielded better biochemical control than 6-month ADT when combined with brachytherapy and EBRT. Therefore, a noninferiority study is warranted to obtain further evidence supporting these preliminary results.

Remote surgical education using synthetic models combined with an augmented reality headset.

Objective: The objective was to investigate the use of an augmented reality headset to remotely train clinicians on medical devices using anatomic models. Design: Disease-specific phantoms were developed to train physicians in mpMRI-guided fusion prostate biopsy, brachytherapy, and rectal spacer insertion. Training was remotely demonstrated using 1-way virtual video conferencing format. Participants responded to an educational content survey. A heads-up display with software and augmented reality was used for remote 2-way training with the proctor and student using on their own phantoms. Setting: The virtual video meeting took place during a prostate cancer conference in 2020, while the augmented reality training occurred in 2021. The proctor and student wore a heads-up display containing a projector and webcam where the ultrasound image was displayed onto a see-through optic along with the physician's hands. The heads-up display allowed the proctor to teach by line-of-sight while the student watched and repeated the steps. Participants: Faculty with expertise with the medical devices used in these procedures provided training to urologists unfamiliar with these techniques. Results: Participants responded that the 1-way training on the phantoms was realistic and mimicked human tissue. A total of 70.9% requested more training or training on the phantoms. The remote training platform was successfully beta tested at the 2 locations in transperineal prostate biopsy and rectal spacer insertion. Conclusion: Remote training using augmented reality eliminates the need for travel. For training programs and workshops, this technology may mitigate the risk of infectious exposures, reduce training cost, and increase proctor availability, allowing training from their own institution or clinic.This investigation qualifies for the Accreditation Council for Graduate Medical Education competency in medical knowledge.

Comparison of AUA and phoenix definitions of biochemical failure following permanent brachytherapy for prostate cancer.

PURPOSE: To compare biochemical recurrence free survival (BCRFS) and cancer-specific survival (CSS) after brachytherapy using the AUA and the Phoenix definitions. METHODS AND MATERIALS: 2634 men with T1-T4N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant hormonal therapy or external beam radiation therapy. Five, 10, and 15- year BCRFS and CSS were estimated with Kaplan-Meier estimates with log rank. Multivariate analysis of survival was performed with Cox regression analysis. RESULTS: Median age was 66, follow-up was 8.6 years, and prostate specific antigen was 6.9. Overall, 11.1% (n = 293) of patients experienced Phoenix BCR and 17.48% (n = 457) experienced AUA BCR. The rates of AUA BCR and Phoenix BCR were significantly different at 5 and 10-years but not at 15 years. Patients treated with BED ≤ 200 Gy were more likely to experience AUA BCR (22.5% vs. 12.4%, OR 1.44, p < 0.001) and Phoenix BCR (14.3% and 8.3%, OR 1.37, p < 0.001) than patients treated with a BED > 200 Gy. CONCLUSIONS: Compared to the Phoenix definition, the AUA definition of BCR after brachytherapy is associated with significantly worse BCRFS for the first 15 years after treatment. Receiving a BED > 200, which cannot be achieved without the addition of brachytherapy, is associated with better BCRFS and CSS. Our findings reaffirm the importance of dose in the management of prostate cancer.

Factors associated with late local failure and its influence on survival in men undergoing prostate brachytherapy.

BACKGROUND AND PURPOSE: To determine the factors associated with a positive post-treatment prostate biopsy (PB) and the effects of local failure on biochemical control and cause-specific survival (CSS) in men receiving prostate brachytherapy. METHODS AND MATERIALS: Of 545 men with post-implant PB, 484 were routine (median 24 months) while 61 (median 55 months) were for cause. 114 had a repeat PB for rising PSA. Initial mean PSA was 10.5 ng/ml (±13.9) while 244 (44.8%), 202 (37.1%) and 99 (18.2%) had low, intermediate or high-risk disease. Treatments were implant only in 287 (52.7%), and implant with androgen deprivation therapy (ADT) ± external beam in 258. Radiation doses were converted to the biologically equivalent dose (BED). Final biopsy results were the last biopsy performed on that patient. Associations for the first and final biopsies with PSA, clinical stage (CS), Gleason grade group, time on hormone therapy (ADT) and BED were determined by ANOVA, chi-square and binary linear regression. Freedom from Phoenix failure (FFPF) and cause-specific survival were estimated by Kaplan Meier method and Cox proportions hazards. RESULTS: After a median of 11.4 years the first and final biopsy were positive in 10.8% and 8.8%, respectively. Significant linear regression associations with first positive PB were ADT (p = 0.005), CS (p = 0.044) and BED (p = 0.030) while only BED (p < 0.001) was significant for the final PB. Positive biopsy occurred in 21/112 (18.8%), 16/230 (7.0%) and 3/182 (1.6%) for BED ≤150, >150-200 and >200 Gy (p < 0.001), and in 29/261 (11.1%) for BED (median) ≤185 Gy vs. 5/263 (1.9%) for > 185 Gy (OR 4.2, p < 0.001). 15-year FFPF was 75.6 vs. 17.5% and cause-specific survival was 94.2 vs. 75.5% for negative vs. positive biopsy. CONCLUSIONS: Higher radiation doses are associated with 1.9% late local failure following prostate brachytherapy. A negative post-implant PB is associated with superior FFPF and decreased prostate cancer mortality.

Transperineal prostate biopsy identifies locations of clinically significant prostate cancer in men considering focal therapy with PI-RADS 3-5 regions of interest.

Objectives: To determine the benefit of performing transperineal prostate mapping biopsy (TPMB) following multiparametric magnetic resonance imaging (mpMRI) to increase the identification of clinically significant prostate cancer (csPCa) with Gleason grade group (GG) ≥ 2 and their locations outside of the PI-RADS v2 3-5 category lesions. Methods: mpMRI was performed in 80 men prior TPMB from two institutions. The mpMRI was considered clinically significant (csMRI) if it contained one or more PI-RADS 3-5 category lesion. mpMRI findings were compared against csPCa diagnosed by TPMB, performed between 16 November 2010, and 13 September 2019, for the entire gland, both lobes and to the right and left anterior and right and left posterior quadrants (RA, LA, RP and LP). Sensitivity, specificity, positive and negative predictive values (PPV, NPV), accuracy and the area under curve (AUC) were determined. Thirteen men also underwent radical prostatectomy and had comparison of TPMB pathology to prostatectomy specimen grading. Results: TPMB was positive in 60/80 (75%) of which 32 (53.3%) were csPCa. csPCa was present in the RA in 9 (11.3%), LA in 11 (13.8%), RP in 25 (31.3%) and LP in 27 (33.8%) and involved 1 quadrant in 7 (21.9%), 2 quadrants in 12 (37.5%), 3 quadrants in 11 (34.4%) and all 4 quadrants in 2 (6.3%) patients; 57/80 (71.3%) men had a mpMRIs with lesions designated as PI-RADS 3 in 24 (30%), 4 in 25 (31.3%) and 5 in 8 (10%). A csMRI was present in the RA in 7 (8.8%), LA in 8 (10%), RP in 31 (38.8%) and in the LP in 29 (36.3%), which were limited to one quadrant in 39 (68.4%), 2 quadrants in 16 (28.1%), and 3 quadrants in 2 (3.5%). Sensitivity, specificity, PPV, and NPV were determined from the results of the TPMB and were for the entire gland 81.3%, 35.4%, 45.6% and 73.9%. There were 31 csMRIs involving the right posterior of the gland but only 25 csPCa by TPMB of which 12/31 (38.7%) were concordant for high grade disease. There were 29 men who have a csMRI in the left posterior quadrant, and 14 (48.3%) were concordant with csPCa from the TPMB. Conclusions: MpMRI should be supplemented with TPMB to correctly identify the regions of the prostate that would require ablation in men considering focal therapy.

I-125 or Pd-103 for brachytherapy boost in men with high-risk prostate cancer: A comparison of survival and morbidity outcomes.

PURPOSE: Brachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy. METHODS AND MATERIALS: Of 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ2 test with survival determined by the Kaplan-Meier method and Cox regression. RESULTS: Men treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150-200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes. CONCLUSIONS: Brachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival.

Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation.

PURPOSE: Men with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT). METHODS AND MATERIALS: Three hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan-Meier method with associations determined by log rank and Cox regression. RESULTS: Ten-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001). CONCLUSIONS: Survival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT.

Prolonged hormonal therapy and external beam radiation independently increase the risk of Persistent Hypogonadism in men treated with prostate brachytherapy.

PURPOSE: To identify variables that predict persistent hypogonadism and castration in patients with prostate cancer (PCa) treated with brachytherapy (BT). MATERIALS AND METHODS: A retrospective analysis was performed on 1,053 patients receiving BT ± external beam radiation therapy (EBRT) ± hormone therapy (HT) for NCCN low, intermediate, or high-risk PCa between 1990 and 2011. Patients were categorized as not receiving HT (n = 438, 41.6%), ≤6 months (n = 317, 31.1%) or > 6 months (n = 298, 28.3%) of HT. 572 (54.3%) received BT alone, and 481 had combination therapy. The five- and 10-year freedom from persistent hypogonadism (T < 280 ng/dL) and castration (T < 50 ng/dL) for each group was evaluated with Kaplan-Meier estimates. Multivariable cox proportional hazards models were used to compare the risk of persistent hypogonadism and castration at a median followup of 6.5 years (posttreatment to final T) (IQR: 4.3-9.1 years; range: 1.0-19.2 years). RESULTS: The 5-year freedom from hypogonadism rates were 92.4%, 88.9%, and 87.0% for patients with no HT, ≤ 6 months and >6 months of HT, respectively (10-year rates: 66.7%, 55.3%, 40.5%); p < 0.01. The 5-year freedom from castration rates were 99.2%, 98.0%, and 98.4%, respectively (10-year rates: 97.9%, 95.5%, 90.9%); p = 0.078. Number of months of HT (HR = 1.04, p = 0.030) and BT with EBRT vs. BT alone (HR = 1.56, p = 0.010) significantly increased the risk of persistent hypogonadism. Number of months of HT was the only variable which increased the risk of persistent castration (HR = 1.09, p = 0.014). CONCLUSIONS: The addition of EBRT to BT is an independent risk factor for persistent hypogonadism. Prolonged HT additionally increases the risk of persistent hypogonadism and castration.

Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy.

BACKGROUND: A total of 10%-20% of patients develop long-term toxicity following radiotherapy for prostate cancer. Identification of common genetic variants associated with susceptibility to radiotoxicity might improve risk prediction and inform functional mechanistic studies. METHODS: We conducted an individual patient data meta-analysis of six genome-wide association studies (n = 3871) in men of European ancestry who underwent radiotherapy for prostate cancer. Radiotoxicities (increased urinary frequency, decreased urinary stream, hematuria, rectal bleeding) were graded prospectively. We used grouped relative risk models to test associations with approximately 6 million genotyped or imputed variants (time to first grade 2 or higher toxicity event). Variants with two-sided Pmeta less than 5 × 10-8 were considered statistically significant. Bayesian false discovery probability provided an additional measure of confidence. Statistically significant variants were evaluated in three Japanese cohorts (n = 962). All statistical tests were two-sided. RESULTS: Meta-analysis of the European ancestry cohorts identified three genomic signals: single nucleotide polymorphism rs17055178 with rectal bleeding (Pmeta = 6.2 × 10-10), rs10969913 with decreased urinary stream (Pmeta = 2.9 × 10-10), and rs11122573 with hematuria (Pmeta = 1.8 × 10-8). Fine-scale mapping of these three regions was used to identify another independent signal (rs147121532) associated with hematuria (Pconditional = 4.7 × 10-6). Credible causal variants at these four signals lie in gene-regulatory regions, some modulating expression of nearby genes. Previously identified variants showed consistent associations (rs17599026 with increased urinary frequency, rs7720298 with decreased urinary stream, rs1801516 with overall toxicity) in new cohorts. rs10969913 and rs17599026 had similar effects in the photon-treated Japanese cohorts. CONCLUSIONS: This study increases the understanding of the architecture of common genetic variants affecting radiotoxicity, points to novel radio-pathogenic mechanisms, and develops risk models for testing in clinical studies. Further multinational radiogenomics studies in larger cohorts are worthwhile.

Transperineal mapping biopsy improves selection of brachytherapy boost for men with localized prostate cancer.

PURPOSE: To determine if transperineal mapping biopsy (TPMB) can improve the selection of brachytherapy alone (BT) or brachytherapy boost (BTB) in men with localized prostate cancer. METHODS AND MATERIALS: Two hundred and eighteen men underwent TPMB with a mean of 48.6 cores retrieved. Comparisons were made between prebiopsy risk features and biopsy results to treatment choice with associations tested with ANOVA (bootstrap), χ2 test (Pearson), and linear regression. Survival estimates were tested by the Kaplan-Meier method with comparisons by log rank. RESULTS: Mean age, prostate specific antigen (PSA), prostate specific antigen density (PSAD), and prostate volume were 67.2 years, 8.1 ng/mL, 0.19, and 50.3 cc, respectively. 105 (48.2%) biopsies were positive for Gleason Group (GG) 1: 34 (32.4%), 2: 21 (20%), 3: 31 (29.5%), 4: 7 (6.7%), and 5: 12 (11.4%). The mean number of positive cores (PCs) was 7.3 (median 6, range 1-37). Men with six or more PCs had higher PSA (11.3 vs. 6.0 ng/mL, p = 0.025) and PSAD (0.34 vs. 0.13, p = 0.013). Overall brachytherapy was used in 74 (70.5%) as either monotherapy or boost therapy. Men with BTB had higher PSA (9.7 vs. 6.7 ng/mL, p = 0.029), PSAD (0.27 vs. 0.16, p = 0.007), GG (3.3 vs. 1.8, p < 0.001), more bilateral disease (75.9% vs. 55.6%, odds ratio 3.9, p = 0.008), and PCs (10.9 vs. 4.4, p < 0.001). On linear regression, only GG (p = 0.008) and PCs (p = 0.044) were associated with BTB. Biochemical-free failure at 5 years was 92.7%. CONCLUSIONS: TPMB improves the selection of patients for BTB. Men with more PCs are more likely to have BTB. Restricting the need for BTB to those with greater volume prostate cancer may reduce radiation side effects.

The Ratio of the Number of Biopsy Specimens to Prostate Volume (Biopsy Density) Greater Than 1.5 Improves the Prostate Cancer Detection Rate in Men Undergoing Transperineal Biopsy of the Prostate.

PURPOSE: We sought to determine the minimum number of transperineal prostate mapping biopsies needed to optimize the prostate cancer detection rate. MATERIALS AND METHODS: A total of 436 men underwent transperineal prostate mapping biopsy at 2 institutions. Biopsy density was calculated as the ratio of the total number of specimens retrieved (mean 59.4) to prostate volume (mean 44.9 cc). Associations of biopsy density with prostate specific antigen, prostate specific antigen density, cancer diagnosis and the Gleason score were tested by ANOVA and the chi-square test. Regression analysis was done to determine factors associated with a positive transperineal prostate mapping biopsy and Gleason score 7 or higher cancer. RESULTS: Transperineal prostate mapping biopsy was positive in 299 of 436 men (68.6%). The mean number of positive cores was 7.1 (range 1 to 41) and mean biopsy density was 1.46 (range 0.39 to 3.67). The mean number of cores in positive vs negative transperineal prostate mapping biopsies was 1.61 vs 1.14 (p <0.001). Biopsy density cut points of 0.5 or less, greater than 0.5 to 1.0, greater than 1.0 to 1.5 and greater than 1.5 were associated with positive biopsy in 25%, 37.4%, 70.7% and 84.9% of patients (p <0.001). Dichotomizing biopsy density to 1.5 or less vs greater than 1.5 resulted in a positive biopsy rate of 56.4% vs 84.9% (OR 1.5, 95% CI 1.3-1.7, p <0.001). More Gleason score 6 cancers were diagnosed with higher biopsy density (94 of 158 or 59.5% vs 62 of 141 or 44.9%, p = 0.007). However, the number of positive cores with Gleason score 6 was greater in men with higher biopsy density at 4.9 vs 3.6 (p = 0.036). Prostate specific antigen (p = 0.053) and biopsy density (p = 0.012) were significant on regression analysis for positive transperineal prostate mapping biopsy and Gleason score 7+ disease. CONCLUSIONS: Biopsy density greater than 1.5 increases the diagnosis of prostate cancer by 1.5 times, detects higher volume Gleason score 6 disease and should be considered the optimal sampling approach when performing transperineal prostate mapping biopsy.

Permanent prostate brachytherapy is safe in men with severe baseline lower urinary tract symptoms.

PURPOSE: To evaluate the long-term urinary outcomes of men with severe pretreatment lower urinary tract symptoms (LUTS) treated with permanent prostate brachytherapy (PPB) ± external beam radiation therapy for localized prostate cancer. METHODS AND MATERIALS: A total of 105 men with International Prostate Symptom Score (IPSS) 20-35 before PPB were categorized by IPSS change at last followup: (1) worse = IPSS rise >3; (2) no change = IPSS change within three points of baseline; (3) improved = IPSS fall by >3 points. We then evaluated patients who worsened vs. those who did not (no change or improved) with respect to incontinence outcomes, LUTS medication usage, and predictors of symptom worsening. RESULTS: Mean followup was 80.3 ± 55.8 months. Mean age was 66.3 ± 7.1 years; mean pretreatment IPSS was 23.6 ± 3.0. Overall mean improvement in IPSS was 7.6 ± 9.3. Specifically, 14.3% (15/105) worsened, 21.9% (23/105) had no significant change, and 63.8% (67/105) improved. There were no patient- or treatment-related factors significantly associated with long-term worsening of urinary symptoms. No men required anticholinergic therapy at last followup, whereas 7% (8/105) were using an alpha blocker. Only 2.9% (3/105) of men were using at least one pad daily at last followup. Alternatively, only 7.7% (8/105) reported subjective incontinence. CONCLUSIONS: PPB is an acceptable option in the setting of severe baseline LUTS in appropriately selected and counseled patients when performed by a skilled practitioner.

Long-term oncological and functional outcomes support use of low-dose-rate brachytherapy with or without external beam radiation in young men (≤60 years) with localized prostate cancer.

PURPOSE: To evaluate the oncological and functional outcomes of young men treated with low-dose-rate brachytherapy (BT) for prostate cancer (PCa). MATERIALS AND METHODS: 423 men aged ≤60 years with clinically localized PCa were treated with BT ± external beam radiation. Biochemical failure was defined by Phoenix criteria. Freedom from biochemical failure (FFbF) and cancer-specific survival (CSS) at 10 and 15 years were estimated by the Kaplan-Meier method with the log-rank test to compare outcomes between National Comprehensive Cancer Network risk groups. The Cox proportional hazards model was used to determine significant predictors for FFbF and CSS. RESULTS: Median followup was 9.9 years (range, 5.1-21.7). Median age was 57 years (range, 39-60), and median prostate-specific antigen was 6.1 ng/mL (range, 0.8-71). Overall, 10- and 15-year FFbF rates were 89% and 88%; 10- and 15-year CSS rates were 99% and 98%. Increasing disease risk was associated with lower FFbF and CSS (p < 0.0001). Biologically effective dose (p < 0.0001) and use of external beam radiation (p = 0.005) were significantly associated with higher FFbF. In men potent before BT, 64% (151/237) had preserved erectile function at a median 10.2 years. There was no significant difference between treatment groups with respect to long-term urinary function (p = 0.56). CONCLUSIONS: Younger men treated with BT experience excellent long-term PCa control with low rates of treatment-related toxicity.

Stage T3b prostate cancer diagnosed by seminal vesicle biopsy and treated with neoadjuvant hormone therapy, permanent brachytherapy and external beam radiotherapy.

OBJECTIVES: To report the long-term results of prostate brachytherapy followed by external beam radiotherapy (EBRT) in men with a positive seminal vesicle biopsy (+SVB). PATIENTS AND METHODS: In all, 1081 men with localised prostate cancer were treated with permanent brachytherapy, of which 615 had staging SVB and 53 (9.4%) were positive. Higher stage, Gleason score and PSA level were associated with a +SVB (P < 0.001). Patients with +SVB and negative laparoscopic pelvic lymph node dissection, bone and CT scans had 3 months of androgen-deprivation therapy (ADT) followed by 103 Pd implant to the prostate (dose 100 Gy) and proximal SVs, and 2 months later 45 Gy EBRT. ADT was continued for a median of 6 months (total ADT 9 months). The mean (range) follow-up was 9 (5-22) years. RESULTS: Biochemical freedom from failure (computed by the Phoenix definition), freedom from metastasis, and cause-specific survival (CSS) for patients with a negative SVB (-SVB) vs +SVB at 15 years, was 76.3% vs 60.6% (P = 0.001), 95.4% vs 78.2% (P < 0.001), and 95% vs 70.4% (P < 0.001), respectively. Prostate cancer death occurred in 45 of 590 (7.6%) men with a -SVB vs eight of 25 (32%) with a +SVB (odds ratio 5.7, 95% confidence interval 2.35-13.9, P < 0.001). Cox proportion hazard rates (HRs) demonstrated Gleason score (P < 0.001, HR 1.9), stage (P = 0.010, HR 1.42), RT dose (P = 0.013, HR 0.991), and +SVB (P = 0.001, HR 4.48), as significantly associated with CSS. CONCLUSIONS: Men with a +SVB have inferior CSS compared to those with a -SVB. However, a strategy that included a SVB in high-risk patients and implantation of the SVs in men undergoing combined therapy still yields favourable long-term results.

Prostate-specific antigen doubling time is a significant predictor of overall and disease-free survival in patients with prostate adenocarcinoma treated with brachytherapy.

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

Transrectal Ultrasound-guided Versus Transperineal Mapping Prostate Biopsy: Complication Comparison.

Herein, the authors compare morbidity in men who underwent both transrectal ultrasound-guided (TRUS) prostate biopsy and transperineal mapping biopsy (TPMB) at two institutions with extensive experience in both procedures. We also identified strategies and predictive factors to reduce morbidity for both procedures. In our study, 379 men from two institutions, of which 265 (69.9%) had a prior TRUS-guided biopsy, also had TPMB performed via a template with biopsies taken at 5-mm intervals. Men in the TRUS group had a median of 12 cores sampled whereas the TPMB group had 51.5 (range, 16-151). The median biopsy density was 1.1 core/cc prostate volume. Median age and prostate-specific antigen (PSA) level were 65 years (range, 34-86) and 5.5 ng/mL (range, 0.02-118). Of these men, 11 of 265 (4.2%) who had TRUS biopsy developed urinary tract infection compared with 3 of 379 (0.79%) of those with mapping biopsy. Infection was 14.8% in TRUS biopsy group with 13 or more cores versus 2.9% in those with 12 or less (OR, 5.8; 95% CI, 1.6-21.2; P = 0.003). No men developed retention after TRUS biopsy whereas 30 of 379 (7.9%) did following TPMB. Older age, larger prostate volume (PV), and higher core number were associated with retention. On linear regression only age (P = 0.010) and PV (P = 0.016) remained as significant associations. Men older than 65 years had 12.8% versus 3.9% (OR, 3.7; 95% CI, 1.6-8.4, P = 0.001) and PV greater than 42 cc had 13.4% versus 2.7% (OR, 5.7; 95% CI, 2.1-15.1) retention incidence. In the present study TPMB is rarely associated with infection (0.78%) but more commonly with urinary retention (7.9%). Men older than 65 years and with PV greater than 42 cc were at four to five times greater retention risk. Consideration should be given to discharging these men with a urinary catheter following TPMB.