The use of hydrogel spacer in men undergoing high-dose prostate cancer radiotherapy: results of a prospective phase 2 clinical trial.

PURPOSE: The purpose of this study was to determine whether the degree of prostate to rectal separation using a hydrogel spacer (HS) and its effect on decreasing rectal dose can be reproduced in the community setting. METHODS: Thirty one patients with cT1-3aN0M0 prostate adenocarcinoma receiving radical radiotherapy to 78 Gy were recruited to the study. The primary endpoint was the proportion of patients achieving at least 25% reduction in volume of rectum receiving 70 Gy (rV70). Other endpoints included degree of prostate to rectum separation, HS insertion-related adverse events and the proportion of patients with grade 1 or worse acute or late gastrointestinal (GI) and genitourinary (GU) toxicity. RESULTS: All patients had successful insertion of their HS with no peri-operative toxicity. The mean prostate-rectal separation achieved was 10.5 mm. Twenty nine (93.5%) patients achieved a reduction in rV70 of at least 25%. Acute grade 1 GI toxicity was reported in 3 patients. All symptoms had resolved by 3 months post RT. Late grade 1 GI toxicity was reported in one patient (3.2%) with bowel frequency occurring at 6 months and resolving by 12 months post RT. There was no grade 2 or 3 acute or late GI toxicity seen. CONCLUSION: In conclusion, this study illustrates that the application and benefits of HS on reducing GI rectal dose endpoints and toxicities during prostate cancer RT can be reliably replicated in a community setting similar to centres participating in the randomised trial under high quality assurance trial monitoring.

Low-dose-rate brachytherapy and long-term treatment outcomes in patients younger than 60 years of age.

Purpose: Low-dose-rate (LDR) brachytherapy in young men remains controversial amongst urologists due to their concerns regarding long-term biochemical control and treatment-related toxicities. The purpose of this study was to evaluate the treatment outcomes of men under 60 years of age who underwent LDR brachytherapy with iodine-125 (125I) for clinically localized low- to intermediate-risk prostate cancer. Material and methods: All consecutive patients with clinically localized prostate cancer treated at our institution from 2003 to 2016 with 125I monotherapy were included in the study. Prescription dose was 145.0 Gy modified peripheral loading (MPD). All patients were assessed for biochemical progression-free survival using Phoenix definition (nadir +2 ng/ml), clinical progression-free survival, overall survival (OS), and any associated treatment toxicity. Results: A total of 161 patients were included, with a median follow-up of 6.8 years (range, 3-14.54 years). Median age at implant was 57 years (range, 53-59 years). Mean prostate specific antigen (PSA) level at diagnosis was 4.43 ng/ml (SD = 2.29). Majority of men had low-risk prostate cancer (70.2%). Biochemical progression-free survival at 8 years was 94% for the entire cohort. Median PSA at 4 years was 0.169 (IQR, 0.096-0.360), with 45% of patients having a PSA greater than 0.2. OS was 96.9%, with 5 deaths reported but only one was secondary to prostate cancer. Late grade > 2 genitourinary toxicities were reported in 18 patients (11.2%). Three patients (1.9%) developed secondary cancers, all considered unrelated to their LDR brachytherapy. Conclusions: With excellent long-term treatment outcomes and minimal associated toxicities, our results showed that LDR brachytherapy can be an effective treatment of choice in younger men.

Hyaluronic acid rectal spacer in EBRT: Usability, safety and symmetry related to user experience.

OBJECTIVES: To report on the usability, safety, symmetry, and effectiveness of hyaluronic acid (HA) injected between the prostate and the rectum for patients undergoing treatment for prostate cancer with external beam radiotherapy (EBRT), and present a novel definition of rectal spacer symmetry that is reproducible and independent of patient anatomy. PATIENTS AND METHODS: 102 consecutive patients with clinical stage of T1c-3b prostate cancer underwent general anaesthesia for fiducial marker insertion and injection of HA into the perirectal space before EBRT. HA safety, symmetry, separation, and usability based on user experience were assessed. RESULTS: HA insertion was completed with a 100% success rate independent of user experience, rated as 'easy' or 'very easy' in all cases. There were no postoperative complications reported. The mean (SD) recto-prostatic separation for all patients at the base, midgland and apex were 12 (±2) mm, 11 (±2) mm, and 9 (±1) mm respectively. The mean sagittal length of the implant was 43 (±5) mm. The implant was rated as symmetrical in 98% of cases. The mean rV70Gy was 1.6% (IQR 0.8-3.3%) for patients receiving 78-80Gy. The mean rV53Gy was 2.8% (IQR 1.2-4.8%) for patients receiving 60-62Gy. The median prostate size was 43.5 cc (IQR 32-57). CONCLUSION: Injection of HA was able to achieve highly symmetrical recto-prostatic separation, with new users able to produce excellent separation, particularly at the apex, achieving similar dosimetry outcomes as competent and experienced users. HA is safe, easy to use, and significantly reduced mean rV70Gy and rV53Gy compared to non-spacer patients.

Impact of hydrogel and hyaluronic acid rectal spacer on rectal dosimetry and toxicity in low-dose-rate prostate brachytherapy: a multi-institutional analysis of patients' outcomes.

PURPOSE: To report on rectal dosimetry and toxicity outcomes in men with prostate cancer (PCa) treated with iodine-125 low-dose-rate brachytherapy (LDR-BT) with or without polyethylene glycol hydrogel (HS) or hyaluronic acid (HA) rectal spacer (RS) insertion. MATERIAL AND METHODS: Seventy consecutive men treated with LDR-BT between December 2017 and July 2019 were included in this study, including twenty-eight (40%) men who had RS insertion according to the preference of referring urologist, compared to a group of forty-two men (60%) without RS. Descriptive statistics were used to compare RS safety, dosimetric effects on organs at risk (rectum and urethra), and gastrointestinal (GI) and genitourinary toxicities (GU) (assessed using the CTCAE v.4) between the two groups of patients. RESULTS: The median prostate-rectal separation with RS at mid prostate was 10 mm (IQR, 8-11.5 mm). The median follow-up was 23.5 months. There were no post-operative complications for RS insertion. There was significantly reduced rectal dosimetry in RS-group vs. non-RS group; the median RV100 was 0.0 cc (IQR, 0.0-0.0 cc) vs. 0.4 cc (IQR, 0.1-1.1 cc) (p < 0.001), respectively. The mean rectal D1cc and D2cc were 52.4% vs. 84.2% (p < 0.001) and 45.7% vs. 70.0% (p < 0.001) for RS and non-RS group, respectively. There were no statistically significant differences in the mean urethral D20, D5, and D1. There were significantly less grade 1 acute and late GI toxicities in RS-group when compared to non-RS group (0% vs. 24%, p = 0.004 for acute GI toxicity; 4% vs. 33%, p = 0.003 for late GI toxicity). There were no reported acute or late grade 2 or above GI toxicities. CONCLUSIONS: Insertion of RS in men treated with LDR-BT is safe and resulted in a significant reduction in rectal dosimetry. The reduction in rectal dosimetry with RS insertion translates into significantly reduced acute and late GI toxicities.

The use of tissue fiducial markers in improving the accuracy of post-prostatectomy radiotherapy.

PURPOSE: The aim of this retrospective study was to investigate the use of a radiopaque tissue fiducial marker (TFM) in the treatment of prostate cancer patients who undergo post-prostatectomy radiotherapy (PPRT). TFM safety, its role and benefit in quantifying the set-up uncertainties in patients undergoing PPRT image-guided radiotherapy were assessed. MATERIALS AND METHODS: A total of 45 consecutive PPRT patients underwent transperineal implantation of TFM at the level of vesicourethral anastomosis in the retrovesical tissue prior to intensity-modulated radiotherapy. Prostate bed motion was calculated by measuring the position of the TFM relative to the pelvic bony anatomy on daily cone-beam computed tomography. The stability and visibility of the TFM were assessed in the initial 10 patients. RESULTS: No postoperative complications were recorded. A total of 3,500 images were analysed. The calculated prostate bed motion for bony landmark matching relative to TFM were 2.25 mm in the left-right, 5.89 mm in the superior-inferior, and 6.59 mm in the anterior-posterior directions. A significant 36% reduction in the mean volume of rectum receiving 70 Gy (rV70) was achieved for a uniform planning target volume (PTV) margin of 7 mm compared with the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group recommended PTV margin of 10 mm. CONCLUSION: The use of TFM was safe and can potentially eliminate set-up errors associated with bony landmark matching, thereby allowing for tighter PTV margins and a consequent favourable reduction in dose delivered to the bladder and rectum, with potential improvements in toxicities.

High dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes.

INTRODUCTION: To examine the long-term outcomes of high dose rate brachytherapy boost (HDR-BT) combined with external beam radiotherapy (EBRT) for intermediate and high-risk prostate cancer patients. METHODS: Data from 95 patients who underwent combined EBRT (50.4 Gy) and HDR-BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method. Regression analysis was conducted to identify important predictors of outcomes. RESULTS: A total of 24 patients received an initial HDR-BT dose of 18 Gy in three fractions, with the remaining 71 patients receiving 16 Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow-up was 58 months. The 5-year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P > 0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%. CONCLUSION: The combined HDR-BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre-emptive TURP and/or HS insertion.

Improving rectal dosimetry for patients with intermediate and high-risk prostate cancer undergoing combined high-dose-rate brachytherapy and external beam radiotherapy with hydrogel space.

PURPOSE: To report on rectal dosimetric and toxicity outcomes of intermediate and high-risk prostate cancer patients undergoing combined high-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) with or without hydrogel spacer (HS) insertion. MATERIAL AND METHODS: A total of 97 patients were analyzed in this study, with 32 patients (33%) who had HS insertion compared with a preceding group of 65 patients (67%) without HS. HS safety, the dosimetric effects on organs at risk (rectal, urethral, penile bulb, and bladder) as well as gastrointestinal (GI) and genitourinary toxicity were evaluated and compared between the two groups. RESULTS: The median prostate-rectal separation achieved with HS was 10 mm (range, 5-14 mm). There were no post-operative complications following HS insertion. Patients with HS had significantly lower radiation dose to the rectum across all rectal dose volumes from rV30 to rV80, whether in absolute volume (cc) or as percentage of contoured OAR (p < 0.001). There was also significantly less acute > grade 1 GI toxicity (12.5% vs. 30.8%, p = 0.05) and a trend towards less late grade 1 GI toxicity (0% vs. 7.7%; p = 0.11) in the HS group compared to the non-HS group. CONCLUSIONS: Insertion of HS in prostate cancer patients receiving combined HDR and EBRT is safe and has resulted in a significant radiation dose reduction to the rectum, resulting in significantly less acute GI toxicity and a trend towards less late GI toxicity.

Management and outcomes of Gleason six prostate cancer detected on needle biopsy: A single-surgeon experience over 6 years.

OBJECTIVE: To assess the management and oncological outcomes in men diagnosed with Gleason score (GS) 6 prostate cancer on needle biopsy in a regional centre, as compared with published international data. MATERIALS AND METHODS: A retrospective analysis was conducted of patients who were diagnosed with GS 6 prostate cancer via transrectal ultrasound-guided or transperineal biopsy between June 2009 and September 2015 under the care of a single surgeon. Data were obtained from a prospectively collected database. RESULTS: A total of 166 patients were diagnosed with GS 6 prostate cancer. The mean age was 61 (range 46-79) years, with mean prostate-specific antigen of 6.7 (0.91-26.8) ng/mL at diagnosis. Of 166 patients, 117 (70.5%) patients were enrolled into the active surveillance program with 82 (70%) meeting Prostate Cancer Research International Active Surveillance (PRIAS) criteria, 44 patients underwent immediate definitive treatment (88.6% radical prostatectomy and 9.1% radiotherapy) and five watchful waiting. With a median follow-up of 1.8 years, 37 (31.6%) patients on AS had definitive treatment [30 cases (81%) were attributable to disease progression, 4 cases (10.8%) to an abnormal magnetic resonance imaging result and 3 cases (8.1%) for patient preference]. In the 35 patients who underwent radical prostatectomy immediately after diagnosis, the GS was ≥7 in 29 cases (82.9%), and the final pathology was pT3a in 16 (51.6%) and pT3b in one (2.9%). In patients who underwent radical prostatectomy after being on AS, the proportion of GS ≥7 prostate cancer was 29/32 (90.6%), with pT3a in six (18.8%) and pT3b in three (9.4%) cases. Overall, 23.5% of patients had a multiparametric magnetic resonance imaging scan. CONCLUSION: This single-surgeon cohort of GS 6 prostate cancer patients demonstrates a high proportion of cases managed with active surveillance, with comparable rates to international literature. The majority of cases who underwent immediate definitive treatment had significant disease, indicating that patients are being appropriately selected for active surveillance.

Acute exercise does not cause sustained elevations in AMPK signaling or expression.

PURPOSE: No study has examined the response of skeletal muscle AMP-activated protein kinase (AMPK) signaling beyond the first 3 h after an acute exercise bout in humans. The purpose of this study was to assess AMPK signaling in human skeletal muscle immediately after a single bout of moderate-intensity endurance exercise and 3 and 24 h after the exercise bout. METHODS: We examined AMPK signaling, and protein expression of AMPK alpha, ACC-beta, and nNOS mu in untrained individuals (four females and four males) during the 24-h period after a 60-min bout of moderate-intensity (63 +/- 1% VO2peak) cycling endurance exercise. RESULTS: AMPK alpha2 activity, AMPK alpha2 Thr172 phosphorylation, and ACC-beta Ser222 phosphorylation were increased immediately after exercise. These increases had all returned to basal levels at 3 and 24 h after exercise. Furthermore, an acute bout of exercise did not alter AMPK alpha1, AMPK alpha2, ACC-beta, or nNOS mu protein expression during the 24-h period after exercise. CONCLUSION: Although an acute bout of exercise elicits increases in AMPK signaling, this alone is not sufficient to induce sustained increases in either AMPK signaling or protein expression during the postexercise period.