Brachytherapy For Prostate Cancer Research Articles

Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry

Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry <h3>Purpose/Objective(s)</h3> Combined external beam radiation therapy (EBRT) and prostate brachytherapy is one standard of care for men with prostate cancer. Dosimetric correlation of organ at risk (OAR) has been limited by the lack of spatial registration and differences in biological effectiveness between EBRT and brachytherapy dose. This study utilized a validated technique to spatially combine three-dimensional biological effective dose (BED) distributions from different modalities to more accurately depict a composite dose. We use this technique to correlate dosimetry with genitourinary (GU) and gastrointestinal (GI) toxicity in an effort to propose conservative dosimetric tolerances for OARs during combination therapy for prostate cancer. <h3>Materials/Methods</h3> The study cohort consisted of 144 intermediate and high-risk prostate cancer patients treated with combination therapy. Patients received 45 Gy using IMRT, either by static field or modulated arc, and 100 Gy using ¹⁰³Pd. Dosimetry was converted voxel-by-voxel to BED and combined using deformable image or inherent DICOM registration. Acute and late GU and GI toxicity was scored using CTCAE and correlated with combined BED. Biological effective doses for each toxicity group were compared using analysis of variance (α=0.05). <h3>Results</h3> Using dose methodology, the mean prostate BED was 223.5 ± 24.2 Gy. Mean urethral dose and D10 were 182.5 ± 22.8 and 232.0 ± 37.0 respectively. Mean rectal dose and D2cc were 33.2 ± 7.9 and 86.4 ± 24.4 respectively. CTCAE toxicity is reported in Table 1. Overall, there was minimal grade 3+ toxicity. No statistical differences were noted among any of the toxicity grades and there was no correlation between urethral or rectal dose and toxicity. <h3>Conclusion</h3> This study demonstrates the feasibility of using the spatial combination of biologic effective doses for OARs in combination EBRT and brachytherapy for prostate cancer. In this study cohort, the level of toxicity was generally less than reported elsewhere. This dataset serves as an opportunity to propose using combined constraints as a conservative estimate for future studies to estimate OAR tolerances. Initially, we propose conservative combination constraints equal to one standard deviation below our mean patient dosimetry: Urethra D10 < 160 Gy and Rectum D2cc < 60 Gy. The process of establishing a useful BED between two different treatments can help redefine OAR tolerances and has applicability for other treatment sites with combined therapy such as cervix cancer and re-irradiation.

A Pilot Study of Salvage HDR Brachytherapy in Recurrent Prostate Cancer: 5 Year Toxicity and Outcomes

<h3>Purpose/Objective(s)</h3> Until recently, Androgen Deprivation Therapy (ADT) was the main treatment option for recurrent prostate cancer after primary radiation treatment. However, ADT is not curative and is associated with several side effects. Local ablative therapy can be curative and reduce long-term side effects associated with ADT. We designed a single institution prospective pilot study to evaluate the toxicities and outcomes of HDR brachytherapy as a salvage local therapy. <h3>Materials/Methods</h3> Sixty (60) patients with a biopsy-proven local relapse after a previous treatment with radiation were included in this study. A negative bone scan and CT scan of the abdomen and pelvis at the time of relapse was mandatory. Primary objective was to assess both early and late genitourinary (GU) and gastrointestinal (GI) toxicities. Biochemical disease-free survival (bDFS) was also assessed as a secondary objective. Toxicities were reported using CTCAE v5 scale and the IPSS. Short-course ADT could be used if deemed clinically indicated by the physician. HDR brachytherapy regimen was 32Gy delivered in 4 fractions to the whole prostate and, for the last 10 patients recruited, 27Gy in 2 fractions administered focally, due to concerns with toxicities. CT-based treatment planning using an inverse planning algorithm (IPSA) was performed for patients with whole prostate treatment (n = 50). Real-time ultrasound-based treatment planning was used for patients undergoing focal salvage radiation (n = 10). <h3>Results</h3> Median follow-up was 58.4 months (0.8-106.8 months). GI toxicities were acceptable with 3.6% and 14.5% of patients experiencing early and late grade 2 toxicities. No G3 GI toxicities were reported. Early G2 GU toxicities were overestimated at 100% (all patients used an alpha-blocker in the postoperative setting) and one patient had G3 early toxicity. Late GU toxicities were significant, with 14.5% of patients experiencing late G3 toxicity (10.0% at the last follow-up). Of interest, the use of ADT before HDR brachytherapy (n = 17) was associated with lower GU toxicities (no G3) although the association was not statistically significant (Chi-Square p-value 0.201). Good biochemical control was achieved with a bDFS of 73.9% at 48 months. <h3>Conclusion</h3> Salvage HDR brachytherapy after primary radiation to the prostate offers good biochemical control but at the cost of significant G3 GU morbidities. Patients can benefit from local therapy after primary radiation but whole-gland radiation should be used with caution because of concern with toxicities. Focal therapy to partial gland might be a good alternative to achieve local control and avoid severe toxicities.

Combined Brachytherapy and Ultra-Hypofractionated Radiotherapy for Intermediate-Risk Prostate Cancer: Comparison of Toxicity Outcomes Using a High-Dose Rate (HDR) vs. Low-Dose Rate (LDR) Brachytherapy Boost

<h3>Purpose/Objective(s)</h3> Combined brachytherapy and external beam radiotherapy is an accepted treatment for unfavorable intermediate-risk and high-risk prostate cancer. We compared genitourinary and gastrointestinal toxicity of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy boost when combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT) for prostate cancer. <h3>Materials/Methods</h3> 99 intermediate-risk prostate cancer patients underwent UH-EBRT (5 Gy x 5) combined with brachytherapy HDR (n=59) or LDR (n=40) boost. HDR brachytherapy consisted of 15 Gy using Iridium-192, and LDR brachytherapy consisted of Palladium-103 seed implantation (prescription dose=100 Gy). Median baseline IPSS was 5 for both cohorts. Median follow-up was 29.3 months. Toxicity assessment included Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, International Prostate Symptom Score (IPSS), and bowel symptom assessment. Cumulative incidences were calculated for toxicity outcomes. Fisher exact tests were used to evaluate associations. <h3>Results</h3> Overall incidence of grade 2 genitourinary toxicity at 12 and 24 months was 21% and 29%, respectively. The incidence of grade 2 genitourinary toxicity at 12 and 24 months was higher for LDR cohort compared with HDR cohort (45% versus 5.1%, and 55% versus 11%; p<0.001). No grade ≥3 or 4 toxicities were observed. On MVA, only treatment regimen (LDR versus HDR) was significantly associated with grade ≥2 genitourinary toxicity (p<0.001). Two patients had grade 2 rectal toxicity in each cohort. No grade ≥ 3 or 4 toxicities were observed. <h3>Conclusion</h3> Both LDR and HDR brachytherapy combined with UH-EBRT were associated with favorable toxicity profiles, but significantly less grade 2+ genitourinary toxicity was observed in patients receiving HDR compared with LDR brachytherapy.

Single Fraction HDR Brachytherapy for Prostate Cancer: SiFEPI Phase II Trial Results

<h3>Purpose/Objective(s)</h3> To report the results of the <i>Single Fraction Early Prostate Irradiation</i> (SiFEPI) phase 2 prospective trial. <h3>Materials/Methods</h3> The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and low-intermediate (LIR) risk prostate cancers. After injection of 10 ml of macromolecular hyaluronic acid (rectal spacer), needles were implanted under endorectal ultrasound guidance. After post-implant CT scan, a single fraction of 20 Gy was delivered to the prostate taking into account the dose constraints for CTV and organs at risk (urethra, rectum, anus). Oncological outcome (biochemical (bRFS), local (lRFS), and metastatic (mRFS) relapses and disease-free (DFS), cause-specific (CSS) and overall (OS) survivals), toxicity profile (acute [d30, d90, d180] and late [> 6 months] genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities) were investigated as well as quality of life (QLQ-C30 and QLQ-PR25). <h3>Results</h3> From March 2014 to October 2017, 35 pts were enrolled. Among them, 33 were evaluable. With a median age of 66 y [46 - 79], 25 (76%) and 8 (24%) pts were LR and FIR respectively. Median MRI prostatic volume was 41 cc [19 - 84]. Median peak-urinary flow and post-void residual volume were 17 ml/s [8 - 25] and 19 cc [0 - 165] while 30 pts (91%) had an IIEF score between 16 and 25. Median CTV, D90% and V100% were 50 cc [29 - 92], 106% [104 - 109], and 98% [96 - 99] respectively. With a MFU of 72.8 months [64 - 86], 6y-bRFS, lRFS and mRFS were 62% [45 - 85], 61% [44 - 85] and 93% [85 - 100] respectively while 6y-DFS, CSS and OS were 54% [37 - 77], 100% and 89% [77 - 100]. Acute GU, GI and S toxicities were observed in 27 pts (82%; 36 G1 & 8 G2), 5 pts (15%; 7 G1 & 3 G2) and 5 pts (15%; 3 G1 & 2 G2) respectively and no acute G3 toxicity was observed. Late GU, GI and S toxicities were observed in 11 pts (33%; 18 G1), 4 pts (12%; 4 G1) and 7 pts (21%; 1 G1, 5 G2 & 1 G3) respectively. QLQ-C30 and QLQ-PR25 will be reported later. Biochemical relapse (BR) was observed in 11 pts (33%; 7 LR & 4 FIR) with a median time interval between HDB and BR of 51 months [24 – 69]. Among them, 9 pts (82%) presented a histologically proven isolated local recurrence and underwent salvage prostate re-irradiation delivering a median dose of 78 Gy [73 – 78] (2 Gy/f). With a MFU from salvage EBRT of 27 months [3 – 59], 2^nd bRFS rate was 100%. One pt presented a G3 GU toxicity (hematuria) while no G≥3 GI complication was observed. <h3>Conclusion</h3> Long-term results of the SiFEPI phase 2 prospective trial showed that a single fraction of 20 Gy (HDB) leads to a sub-optimal biochemical control for LR and LIR prostate cancers. The reported oncological outcome is in line with the previous series of HDB single fraction protocols. However, late GU and GI toxicity profile is encouraging (especially compared to iodine implant series), leading to consideration of HDB as a safe irradiation technique. Salvage EBRT appears feasible with an acceptable risk of complications.

Prostate Brachytherapy Utilization in the COVID-19 Era: A Cross-Sectional Study of Radiation Oncologists in the United States

Purpose/Objective(s)Brachytherapy (BT) is indicated as monotherapy for lower risk prostate cancer (PC) or to boost external beam radiation therapy (EBRT) for higher risk disease. Despite its advantages, such as decreased treatment time and cost, BT utilization in the United States (US) is declining. We surveyed US radiation oncologists (ROs) to determine the proportion of providers who offer BT for PC, by risk group, and whether the COVID-19 pandemic influenced practice patterns. We hypothesized that rates of utilization would continue to lag EBRT.Materials/MethodsFrom July-October 2021, an anonymized survey was distributed to currently practicing US ROs. Demographic and practice characteristics were collected. Questions assessing utilization of BT and EBRT for patients of varying risk group and the effect of the pandemic on practice patterns were administered. The primary endpoint was the rate of BT utilization by risk group. Descriptive statistics were performed. The bivariate relationships between provider characteristics and likelihood of offering BT were assessed using 2-sided chi-squared tests (α=0.05).ResultsOf 203 respondents (72% male, 72% white, 53% non-academic, 69% >10 years in practice), 156 (77%) treated PC. For low (41% total; 25% low dose rate [LDR], 10% high dose rate [HDR], 6% both) and favorable intermediate (FI) (37% total; 21% LDR, 10% HDR, 6% both) PC, BT was less commonly offered then stereotactic body (SBRT – 54% and 48%), moderately hypofractionated (MHFRT – 83% and 87%), and conventionally fractionated (CFEBRT – 37 and 38%) radiation therapy. For unfavorable intermediate PC, BT alone (7%) and BT+EBRT (37%) were less offered then moderately HFRT (82%) and CFEBRT (46%). For high and very high-risk PC, BT boost was not routinely offered (44% and 37%, respectively). For every risk group, academic ROs were more likely to offer BT (50-60% vs. 29-46%, all p < 0.05) (Table 1). For FI only, ROs treating both urban and rural patients were less likely to offer BT than those in an urban or rural setting (p=0.045). No other characteristics were associated with offering BT. <1% of respondents reported increased BT usage due to the pandemic.ConclusionDespite its advantages for patients, BT remains underutilized, particularly in non-academic settings, with <1/2 of surveyed ROs offering BT monotherapy for low to FI risk PC or to boost higher risk disease. Practice patterns were unaffected by COVID-19 likely due to barriers to starting a BT program. Provider retraining may be critical to increasing utilization rates.

Deposition of Iodine-125 on Silver Supports of Microsources for Prostate Cancer Brachytherapy

A method of iodine-125 deposition on a surface of microsource silver supports for brachytherapy of prostate cancer was reported, which includes preparing the support surface by sequentially treating them with nitric acid and thiourea solutions, followed by chlorination of the support surface with a chlorinating agent to form silver chloride on the support surface, and substitution of chlorine atoms for 125I atoms by placing supports containin silver chloride on the surface in a solution with 125I ions to create a 125I layer on the support surface. The method described allows fixing 125I on supports with a low activity distribution on each activity-carrying support.

Брахитерапия рака предстательной железы и иммунный ответ.

Introduction. Information about the brachytherapy-induced immune reactions, which can be used for therapeutic purposes, is of great clinical value. Materials and methods. When preparing a review of the literature on the problem of the effect of brachytherap (BT) on immunity in prostate cancer (PCa), the following bibliographic databases were used: PubMed, Science Direct, Scientific Electronic Library of Russia (eLibrary). The search was conducted on the following keywords: «cancer», «prostate cancer», «brachytherapy», «immunity», «immunotherapy». In total, 6 sources were found that were directly related to the effect of BT on immunity in prostate cancer. Results. Clinical data shows that both low-dose and high-dose prostate cancer brachytherapy (BT) cause a systemic immune response. The authors explain the observed increase in the number of serum leukocytes by the induction of an inflammatory reaction in response to tumor irradiation, and the decrease in the number of B cells by the movement of antigen-recognizing B cells from the bloodstream to the irradiation site. In addition, after BT, an increase in the number of activated T-lymphocytes was demonstrated, while the number of myeloid suppressor cells significantly decreased. It has been suggested that a decrease in this indicator can activate T cells: the number of naive CD4+ and CD8+ T lymphocytes significantly increased after local administration of radioactive sources, with a simultaneous decrease in the number of CD4+ and CD8+ memory T cells. The latter may indicate that local radiotherapy stimulates the activation of the thymus and the release of naive T-lymphocytes into the bloodstream, during the migration of memory cells from the bloodstream to the prostate. The described effects reflect the process of «turning on» T-cell immunity after BT. Researchers believe that an increase in the number of activated T-lymphocytes contributes to the activation of antitumor immunity, long-term remission and reduces the likelihood of recurrence of prostate cancer. High-dose BT of localized prostate cancer, as well as probably low-dose BT, cause the transformation of the immunogenic properties of the tumor and lead to pronounced polyclonal infiltration of the prostate, mainly by T cells, which occurs under the control of a large number of «control points». The occurrence of immune cells infiltrates and changes in the signal transmission system between them after BT are reflected by a change in the type of «inflammatory signature of the tumor» (TIS) from «cold» to «hot». After irradiation in the tumor area the number of PD-L1 macrophages usually increases, which is regarded as a marker of the tumor response to the therapy. It is believed that if BT causes an increase in PD1+ expression, and use of checkpoint inhibitors to these patients can give a good therapeutic effect. Conclusion. The available data indicate that BT primes the systemic immune response, leads to activation of T-cell immunity and, as a consequence, antitumor immunity. All this opens up prospects for the development of prostate cancer combined treatment methods, using BT and immunotherapy.

Prostate brachytherapy utilization in the COVID-19 era: A cross-sectional study of radiation oncologists in the United States

PURPOSEDespite advantages such as abbreviated treatment course, brachytherapy (BT) utilization rates for prostate cancer (PC) in the United States (US) are declining. We surveyed practicing US radiation oncologists (ROs) to determine the proportion who offer BT for PC and whether the COVID-19 pandemic influenced practice patterns. MATERIALS AND METHODSFrom July-October 2021, we surveyed practicing US ROs. Provider demographic and practice characteristics were collected. Questions assessing utilization of BT and external beam (EBRT) for patients of varying risk groups and the effect of the pandemic on practice patterns were administered. Descriptive statistics were reported. The bivariate relationships between provider characteristics and likelihood of offering BT were assessed using the Chi-square test (α < 0.05). RESULTSSix percent of surveyed ROs responded, with 203 meeting inclusion criteria (72% male, 72% white, 53% non-academic, 69% >10 years in practice) and 156 (77%) treating PC. For low-risk, fewer providers offered BT (41% total; 25% low dose rate [LDR], 10% high dose rate [HDR], 6% both) than stereotactic body (SBRT) (54%) and moderately hypofractionated radiation therapy (MHFRT) (83%). For favorable intermediate risk, fewer offered BT (37% total; 21% LDR, 10% HDR, 6% both) than SBRT (48%), MHFRT (87%), and conventionally fractionated EBRT (38%). For high (44%) and very-high (37%) risk, fewer offered EBRT+BT than EBRT alone. For every risk group, academic ROs were significantly more likely to offer BT (all p-values<0.05). <1% of respondents reported increased pandemic-related BT usage. CONCLUSIONSUS ROs, particularly in non-academic settings, do not routinely offer BT monotherapy or boost (<50%). Practice patterns were unaffected by COVID-19. Retraining may be critical to increasing utilization.

Transperineal bulbovesical anastomosis for extensive posterior urethral stenoses after treatment of prostatic disease.

We report our surgical experience of transperineal bulbovesical anastomosis (BVA) for extensive posterior urethral stenosis (PUS). Six male patients who had extensive PUS extending from the bulbomembranous urethra to the bladder neck due to prostatic disease treatment and underwent transperineal BVA between 2014 and 2020 were retrospectively reviewed. BVA was performed according to the elaborate perineal approach for pelvic fracture urethral repair with minor modifications. After confirming the absence of recurrent stenosis 6 months postoperatively, the patients were offered artificial urinary sphincter (AUS) placement for subsequent urinary incontinence (UI). Median patient age was 68, and the etiology of PUS was radical prostatectomy for prostate cancer in four patients, brachytherapy for prostate cancer in one, and transurethral resection of the prostate for benign prostatic hyperplasia in one. All patients had been previously treated with multiple transurethral procedures such as urethrotomy and dilation. Median operative time and blood loss were 211 min and 154 ml, respectively. Five cases (83.3%) had no recurrent stenosis with a median follow-up of 45 months, but a single direct vision internal urethrotomy was performed in one (16.7%) due to restenosis. Four (66.7%) patients underwent AUS placement via transcorporal approach for subsequent UI, but two had it removed due to urethral erosion. Transperineal BVA could effectively manage extensive PUS after prostatic disease treatment. Staged AUS placement could be a viable option for subsequent UI, but the risk of urethral erosion seemed high.

50: A Pilot Study of Salvage Hdr Brachytherapy in Recurrent Prostate Cancer: 5 Year Toxicity and Outcomes

50: A Pilot Study of Salvage Hdr Brachytherapy in Recurrent Prostate Cancer: 5 Year Toxicity and Outcomes

MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer.

Background and purposeLocally recurrent prostate cancer after radiotherapy merits an effective salvage strategy that mitigates the risk of adverse events. We report outcomes of a cohort enrolled across two institutions investigating MRI-guided tumor-targeted salvage high dose rate brachytherapy (HDR-BT).Materials and methodsAnalysis of a prospective cohort of 88 patients treated across two institutions with MRI-guided salvage HDR-BT to visible local recurrence after radiotherapy (RT). Tumor target dose ranged from 22-26 Gy, using either an integrated boost (ibBT) or focal technique (fBT), delivered in two implants over a median of 7 days. Outcome metrics included cancer control and toxicity (CTCAE). Quality of life (QoL-EPIC) was analyzed in a subset.ResultsAt a median follow-up of 35 months (6 -134), 3 and 5-year failure-free survival (FFS) outcomes were 67% and 49%, respectively. At 5 years, fBT was associated with a 17% cumulative incidence of local failure (LF) outside the GTV (vs. 7.8% ibBT, p=0.14), while LF within the GTV occurred in 13% (vs. 16% ibBT, p=0.81). Predictors of LF outside fBT volumes included pre-salvage PSA>7 ng/mL (p=0.03) and interval since RT less than 5 years (p=0.04). No attributable grade 3 events occurred, and ibBT was associated with a higher rate of grade 2 toxicity (p<0.001), and trend towards a larger reduction in QoL sexual domain score (p=0.07), compared to fBT.ConclusionA tumor-targeted HDR-BT salvage approach achieved favorable cancer control outcomes. While a fBT was associated with less toxicity, it may be best suited to a subgroup with lower PSA at later recurrence. Tumor targeted dose escalation may be warranted.

Indications for additional volume studies for gland volume estimation in prostate cancer brachytherapy.

An estimated gland volume of > 60cc is a relative contraindication to brachytherapy for prostate cancer. As volume estimation using biopsy ultrasound (Bx-US) alone may be inaccurate, many centers perform additional volume assessments prior to the brachytherapy procedure. At the study institution, computed tomography (CT) based volume assessments were routinely performed on all patients to determine brachytherapy eligibility. This study aimed to determine whether this CT imaging could be omitted for certain Bx-US based gland volume estimates. To investigate this, 1576 consecutive patients that received ultrasound based intraoperatively planned brachytherapy at a single comprehensive cancer center between 2003 and 2021 were reviewed. Gland volume as estimated by Bx-US, CT and magnetic resonance (MR) imaging were compared to intraoperatively contoured gland volume (ICGV) or the larger contoured gland volume on CT for any patients receiving neo-adjuvant androgen deprivation therapy (ADT) for gland downsizing (IM-US-corr). There was a significant difference between IM-US-corr and estimated gland volume for Bx-US (P < 0.001) and MR (P < 0.001), but not CT (P = 0.160). Bx-US and MR tended to underrepresent the IM-US-corr, with a > 20% difference from actual volume in 31% and 59% of cases, respectively. When Bx-US volume was estimated to be < 40cc, < 50cc and < 60cc, an IM-US-corr > 60cc was encountered in 2%, 5% and 7% of cases, respectively. In contrast, IM-US-corr > 60cc was encountered in 0.2%, 1% and 2% of cases for CT estimates of < 40cc, < 50cc and < 60cc. In patients with an estimated gland volume of < 50cc by Bx-US, dedicated pre-operative volume studies are unlikely to alter management. However, patients above this cut-off stand to benefit from the use of additional volume assessment to better delineate gland volume and determine eligibility for brachytherapy.

Single fraction of HDR brachytherapy for prostate cancer: Results of the SiFEPI phase II prospective trial

PurposeTo report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial. Materials/MethodsThe SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated. ResultsFrom 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46–79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64–86], 6y-bRFS, lRFS and mRFS were 62 % [45–85], 61 % [44–85] and 93 % [85–100] respectively while 6y-DFS, CSS and OS were 54 % [37–77], 100 % and 89 % [77–100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24–69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence. ConclusionsLong-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

Contrast-Specific Spherical Lesion Phantoms and Ancillary Analysis Software for the Objective Evaluation of Transrectal Ultrasound System Contrast Detectability.

Brachytherapy is an efficacious treatment option because of its benefits for patient recovery, dose localization and conformity, but these favorable outcomes can be ensured only if the transrectal ultrasound (TRUS) system is optimized for the specific application of ultrasound-guided prostate brachytherapy. The ability to delineate the prostate from surrounding tissue during TRUS-guided prostate brachytherapy is vital for treatment planning, and consequently, so is the contrast resolution. This study describes the development of task-specific contrast-detail phantoms with clinically relevant contrast and spherical target sizes for contrast-detail performance evaluation of TRUS systems used in the brachytherapy procedure. The procedure for objective assessment of the contrast detectability of the TRUS systems is also described; a program was developed in MATLAB (R2017a, The MathWorks, Natick, MA, USA) to quantitatively analyze image quality in terms of the lesion signal-to-noise ratio (LSNR) and validated with representative control test images. The LSNR of the Hitachi EUB-7500A (2013, Hitachi, Ltd, Tokyo, Japan) TRUS system was measured on sagittal and transverse TRUS images of the contrast-detail phantoms described in this work. Results revealed the efficacy of the device as an image quality evaluation tool and the impact of the size, depth and relative contrast of the targets to the surrounding tissue on the contrast detectability of a TRUS system for both transducer arrays. The MATLAB program objectively measured the contrast detectability of the TRUS system and has the potential to determine optimized imaging parameters that could be designed as part of standardization of the imaging protocol used in TRUS-guided prostate brachytherapy for prostate cancer.

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

To compare biochemical recurrence free survival (BCRFS) and cancer-specific survival (CSS) after brachytherapy using the AUA and the Phoenix definitions. 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. 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. 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.

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with 125I brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan–Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making.Study identifier at ClinicalTrials.gov: NCT01492751.

Subclinical inflammation as a predictor for erectile dysfunction after brachytherapy for localized prostate cancer

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR), a marker for subclinical inflammation, has been previously shown to be associated with erectile dysfunction (ED). We studied the potential predictive value of the NLR on ED after prostate brachytherapy (PB) for PCa.METHODS AND MATERIALS: Between July 2005 and January 2021, 842 patients were included in this retrospective study of a prospectively maintained database. ED was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) physician-reported scale. ED was defined as a Grade 2 or 3 function. NLR count was determined 1–2 months before PB and separated into values PB <2 and ≥2. Patient characteristics and erectile function at last follow-up were compared for patients with a Univariate and multivariate analyses were performed to evaluate the predictive value of baseline NLR ≥2 on post-PB ED.RESULTS: Baseline NLR ≥2 was found to be a statistically significant predictor of post-PB ED on both univariate (p = 0.002) and multivariate analyses (p = 0.008). Furthermore, the difference in ED prevalence between the NLR <2 and NLR ≥2 groups became more pronounced with longer follow-up after PB. The ED rate at 5 years post-PB was 43% for the NLR ≥2 groups, compared to 29% for the NLR <2 groups.CONCLUSIONS: Subclinical systemic inflammation is a potentially important factor for predicting sexual toxicity after pelvic radiotherapy. NLR may be used as a proxy for predicting post-PB ED.

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

PURPOSETo 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 MATERIALSA 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. RESULTSThe 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. CONCLUSIONSIn 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.

Combined brachytherapy and ultra-hypofractionated radiotherapy for intermediate-risk prostate cancer: Comparison of toxicity outcomes using a high-dose-rate (HDR) versus low-dose-rate (LDR) brachytherapy boost

Purpose/ObjectiveTo compare toxicity profiles of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT). Materials/Methods99 patients with intermediate-risk prostate cancer underwent an HDR (n = 59) or LDR (n = 40) boost combined with UH-EBRT (5 Gy x 5) . HDR (Ir-192) was delivered a single dose (15 Gy) and LDR (Pd-103) prescription dose was 100 Gy. Median baseline IPSS was 5 for both cohorts. Median follow-up was 29.3mos. Cumulative incidences were calculated for toxicity. Fisher exact tests were used to evaluate associations. ResultsOverall incidence of grade 2 genitourinary toxicity for the entire cohort at 12 and 24 months was 21% and 29%, respectively. The incidence of grade 2 genitourinary toxicity at 12 and 24 months was higher for LDR cohort compared with HDR cohort (45% vs 5.1% and 55% vs 11%; p<0.001). On MVA, only treatment regimen (LDR versus HDR) was associated with grade 2+ genitourinary toxicity (p<0.001). Two patients experienced grade 2 rectal toxicity in each cohort. No grade > 3 toxicities were observed. ConclusionsBoth LDR and HDR brachytherapy combined with UH-EBRT had favorable toxicity profiles, but significantly less grade 2+ genitourinary toxicity was observed in patients receiving HDR.

A Prospective Study of Magnetic Resonance Imaging-guided Focal Salvage High-dose-Rate Brachytherapy for Radiorecurrent Prostate Cancer: Updated Results of 30 Patients

PurposeLimited prospective data on focal salvage high-dose-rate (HDR) prostate brachytherapy is available. We sought to explore the toxicities, health-related quality of life (HRQoL), and efficacy of focal salvage HDR brachytherapy in a prospective clinical trial. This report presents the updated results of previously published data. Methods and MaterialsPatients with locally recurrent prostate cancer after previous external beam radiation therapy and/or brachytherapy were enrolled. Patients received magnetic resonance imaging (MRI)-guided, ultrasound-based focal HDR brachytherapy delivered over 2 fractions of 13.5 Gy delivered 1 to 2 weeks apart. Androgen deprivation therapy (ADT) was not used. ResultsThirty patients were treated between 2012 and 2019. At a median follow-up time of 39 months, the 3-year biochemical failure-free rate was 61.8% (95% confidence interval, 44.0%-86.6%), and the 3-year ADT/salvage therapy-free rate was 86.0% (95% confidence interval, 74.1%-99.8%). Seventeen patients experienced subsequent biochemical failure, 9 received ADT and/or further local salvage, and no patients died of prostate cancer. Of the 28 patients who had posttreatment MRI, 26 had a local treatment response. No acute grade ≥3 genitourinary/gastrointestinal toxicity was observed. One temporary late grade 3 genitourinary toxicity event occurred, but no late grade ≥3 gastrointestinal toxicity was seen. No significant decline in urinary or bowel HRQoL was observed. ConclusionsFocal salvage HDR brachytherapy has a favorable side effect profile, no significant decline in HRQoL, and the 3-year biochemical control rates are in line with those of other salvage options. Early MRI response at the treated site is common, but does not preclude subsequent biochemical failure.