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To assess the long-term treatment efficacy of low-dose-rate (LDR) brachytherapy for the treatment of localized prostate cancer.Cause-of-death annotation in our prospective database was supplemented with death certificate information obtained via an internal audit of patients treated from 1999 to 2017 with LDR prostate brachytherapy as monotherapy or as combination with androgen deprivation therapy and/or external beam radiotherapy. Overall and disease-specific survival were the primary outcomes, estimated with Kaplan-Meier and competing risks multi-state models. Clinical variables influencing mortality were assessed with Cox proportional hazards regression in a sub-analysis of men to assess the predictive value of prostate-specific antigen (PSA) level at 48 months post implant.The audit process began in October 2017 and culminated in June 2020 with a curated series of 2936 patients. All-cause and prostate cancer-specific death prevalence were 11% and 2.9%, respectively. The median (range) follow-up time was 10 (3-21) years and the median (range) time to death from any cause was 9 (3-21) years. At 15 years post implant the overall and prostate cancer-specific survival probability were 81% and 95%, respectively. The 15-year cumulative incidence rates of death not due and due to prostate cancer were 14% and 5%, respectively. A greater risk of death due to prostate cancer was conferred by increasing age at therapy (hazard ratio [HR] 1.1, P 0.001), advanced clinical stages relative to T1a-T2a (HR 1.9, P = 0.048 for T2b; HR 2.7, P = 0.023 for T2c-T3b) and a 48-month PSA level1.0 ng/mL (HR 6.8, P 0.001).This study constitutes the largest retrospective analyses of long-term mortality outcomes from prospectively collected prostate brachytherapy data and confirms the excellent treatment efficacy of LDR prostate brachytherapy for localized prostate cancer. T2 clinical stage subdivisions and 48-month PSA level1.0 ng/mL appear to be strong indicators of prostate cancer-related survival.

BACKGROUND: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa. METHODS: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion. RESULTS: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1–31.3] and 24.2 (IQR 17.9–30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12–24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF). CONCLUSIONS: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12–18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience.

Purpose To determine if Live Implant Dosimetry (LIDO) utilizing intraoperative transrectal ultrasound (TRUS) is equivalent to postimplant CT dosimetry (either day 0 or day 30) in patients with localized prostate cancer (PC) treated with low dose rate (LDR) prostate seed brachytherapy. Methods and Materials The treated population consisted of 628 men with localized (T1-T2) PC. All d'Amico risk categories (low, intermediate, and high) were included, and 437 patients were treated with monotherapy (160 Gy) [low and low tier intermediate], and the remainder (191) [high tier intermediate and high risk] with an implant boost (106 Gy) post external beam radiation, to a volume including the prostate and seminal vesicles (46 Gy). LIDO with intraoperative TRUS, postimplant CT (day 0 and day 30) were performed in all cases. Prostate volumes (V), V100 (prostate) and dose (D) D90 (prostate), D30 (urethra), and Rectum D2cc, were recorded. No urinary catheter was used on Day 30 CT. Results More than 91.33% of monotherapy patients reached the target D90 according to LIDO while only 82.99% of Day 0 CT and 92.82% of Day 30 CT achieved target D90. When considering V100, monotherapy patients recorded target dosimetry in 90.93%, 82.31%, and 92.02% of cases assessed by LIDO, Day 0 CT and Day 30 CT, respectively. Strong correlations are observed in D90, Rectum D2cc and Urethra D30 across imaging modalities but V100 and V150 were poorly correlated due to the relative quantification of this parameter and high degree of error in measurement. Of all monotherapy patients with satisfactory dosimetry on LIDO, 94.82% reached target D90 at day 30 CT and 94.19% reached target V100. Conclusions LIDO and CT are both effective tools for assessing postimplant dosimetry. Patients with satisfactory LIDO dosimetry are highly likely to have equivalent dosimetry on CT at follow-up, indicating that postimplant CT may be eliminated in PC a patients implanted with this technique.

Metastatic recurrence in an atypical site, such as the perineum, can occur after prostatectomy, cryotherapy, or brachytherapy, but is uncommon. To our knowledge, this is only the third case of perineal recurrence of prostatic cancer along a low dose rate brachytherapy needle track. A 64-year-old man was referred to an urologist with an increased PSA of 6.9 ng/mL in December 2008. There were no urinary symptoms. Prostatic biopsies revealed a Gleason 6 adenocarcinoma (3 + 3), and he was treated with low dose rate brachytherapy in May 2009. Sixty-seven seeds of iodine 125 were loaded under ultrasound control, and the PSA subsequently fell to a nadir of 1.19 ng/mL in November 2015. Eight years (May 2017) after the initial treatment, the PSA rose to 5.2 ng/mL. Pelvic MRI and choline PET revealed a nodule in the region of the left internal obturator muscle. Nodule biopsies confirmed prostatic origin. This perineal recurrence is thus most likely related to seeding of tumour cells along the track of a brachytherapy needle. To our knowledge, this is only the fourth case of perineal recurrence of prostatic cancer along a low-dose rate brachytherapy needle track. Perineal recurrence of prostatic cancer along a LDR brachytherapy needle track can occur. Improved imaging techniques may help to identify this type of recurrence earlier and optimise treatment.

Prostate squamous cell carcinoma (pSCC) rarely develops as a secondary cancer after treatment with low-dose-rate brachytherapy (LDR-BT). There is no established effective treatment for the disease condition. Herein, we present a 78-year-old man who developed pSCC 8 years after LDR-BT. He was subsequently selected to receive a combined multimodal treatment with high-dose-rate interstitial brachytherapy (HDR-ISBT), external beam radiation therapy, and chemotherapy for his pSCC. Eleven months later, he displayed no biochemical failure nor clinical radiographic recurrence. However, MRI detected a newly developed prostatic-rectal fistula (grade 4), and a colostomy was performed to relieve pain and inflammation. To our knowledge, this is the first report to perform a combined multimodal treatment with HDR-ISBT for pSCC suspected as a secondary cancer due to LDR-BT.

The prognostic significance of PSA bounce following definitive radiation therapy remains controversial. To develop a sense of current opinion in this area, we performed a systematic search of the literature based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. In January 2021, we systematically searched PubMed, the Cochrane library, and Scopus for studies that compared patients who had localized prostate cancer with or without PSA bounce after definitive radiation therapy. Our objective was to evaluate the association of PSA bounce with biochemical recurrence-free survival, metastatic-free survival, cancer-specific survival, and overall survival, using multivariate Cox regression analysis. A total of 8881 patients in 10 studies matched the selection criteria for the systematic review and meta-analysis. The number of patients with PSA bounce accounted for 2706 of all 8881 patients (30.5%). PSA bounce was associated with better biochemical recurrence-free survival after definitive radiation therapy (pooled HR: 0.62, 95% CI: 0.54–0.71). Subgroup analyses also showed that PSA bounce was independently associated with decreased risk for biochemical recurrence-free survival in prostate cancer patients treated with low dose rate brachytherapy alone (pooled HR: 0.38, 95% CI: 0.27–0.55) and external beam radiotherapy alone (pooled HR: 0.71, 95% CI: 0.57–0.87). This meta-analysis indicated that PSA bounce after definitive radiation therapy is related to improved outcome in terms of biochemical failure in prostate cancer patients.

Purpose External beam radiation therapy (EBRT) with brachytherapy boost reduces cancer recurrence in patients with prostate cancer compared with EBRT monotherapy. However, randomized controlled trials or large-scale observational studies have not compared brachytherapy boost types directly. Methods and Materials This observational cohort study used linked national cancer registry data, radiation therapy data, administrative hospital data, and mortality records of 54,642 patients with intermediate-risk, high-risk, and locally advanced prostate cancer in England. The records of 11,676 patients were also linked to results from a national patient survey collected at least 18 months after diagnosis. Competing risk regression analyses were used to compare gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, skeletal-related events (SRE), and prostate cancer–specific mortality (PCSM) at 5 years with adjustment for patient and tumor characteristics. Linear regression was used to compare Expanded Prostate Cancer Index Composite 26-item version domain scores (scale, 0-100, with higher scores indicating better function). Results Five-year GI toxicity was significantly increased after low-dose-rate brachytherapy boost (LDR-BB) (32.3%) compared with high-dose-rate brachytherapy boost (HDR-BB) (16.7%) or EBRT monotherapy (18.7%). Five-year GU toxicity was significantly increased after both LDR-BB (15.8%) and HDR-BB (16.6%), compared with EBRT monotherapy (10.4%). These toxicity patterns were matched by the mean patient-reported bowel function scores (LDR-BB, 77.3; HDR-BB, 85.8; EBRT monotherapy, 84.4) and the mean patient-reported urinary obstruction/irritation function scores (LDR-BB, 72.2; HDR-BB, 78.9; EBRT monotherapy, 83.8). Five-year incidences of SREs and PCSM were significantly lower after HDR-BB (2.4% and 2.7%, respectively) compared with EBRT monotherapy (2.8% and 3.5%, respectively). Conclusions Compared with EBRT monotherapy, LDR-BB has worse GI and GU toxicity and HDR-BB has worse GU toxicity. HDR-BB has a lower incidence of SREs and PCSM than EBRT monotherapy.

Purpose Rectal hydrogel spacers have been shown to decrease rectal radiation dose and toxicity. In this study, we compared prostate and rectal dosimetry and acute toxicity outcomes in patients who had and had not received a rectal hydrogel spacer prior to combination therapy with external beam radiotherapy and low-dose-rate brachytherapy. Materials and Methods All patients with intermediate-risk and high-risk prostate cancer who received combination therapy at our institution were identified between 2014 and 2019. Dosimetric outcomes of brachytherapy implants and quality of life (QOL) outcomes were compared between patients who had and had not received a hydrogel spacer. Results A Total of 168 patients meeting our inclusion criteria were identified. Twenty-two patients had received a rectal hydrogel spacer, among whom the mean separation between the rectum and prostate was 7.5 mm, and the V100rectum was reduced by 47% (0.09 cc vs. 0.17 cc, p = 0.04). There was no difference in the percentage of patients achieving a D90 of ≥100 Gy between those who had and had not received a spacer. The mean rate of change in I-PSS and SHIM scores did not differ between the two groups at 2 months after PID. Conclusion LDR brachytherapy appears feasible after the placement of a rectal hydrogel spacer. While there was a significantly reduced V100rectum among patients who had received a hydrogel spacer, there was no statistically significant difference in patients achieving a D90prostate of ≥100 Gy. Although there was no difference appreciated in QOL scores, the length of follow-up was limited in the rectal-spacer group.

Objective To study the efficacy of phosphodiesterase-5 inhibitor tadalafil in attenuating adverse events after low-dose-rate brachytherapy for prostate cancer. Methods This was a randomized open-label trial, conducted at two institutions. Prostate cancer patients undergoing low-dose-rate brachytherapy were randomly assigned to receive tadalafil (study group) or tamsulosin (control group). The primary endpoint was International Prostate Symptom Score for subjective evaluation of lower urinary tract symptoms. Uroflowmetry, postvoid residual urine volume, and Sexual Health Inventory for Men score were the secondary endpoints. Each clinical variable was evaluated during a follow-up period of 1 year after low-dose-rate brachytherapy. Results A total of 107 patients were enrolled in this study, with a final total of 96 patients analyzed. The mean total International Prostate Symptom Score changes at 1, 3, 6, 9, and 12 months after low-dose-rate brachytherapy were +7.4, +7.1, +4.7, +1.5, and +0.8, respectively, in the tamsulosin group, and +8.5, +9.2, +6.4, +4.1, and +1.6, respectively, in the tadalafil group. There were no statistically significant differences in International Prostate Symptom Score with the exception of the score at 9-month follow-up. Moreover, there were no statistically significant differences in any of the uroflowmetry or postvoid residual urine volume findings. The Sexual Health Inventory for Men score in the tadalafil group was significantly higher than that in the tamsulosin group at 6, 9, and 12 months after low-dose-rate brachytherapy. Conclusions Tadalafil could be an effective option for the management of lower urinary tract symptoms after low-dose-rate brachytherapy.

Purpose Prostate cancer with nodular bladder invasion (stage T4 prostate cancer) is an extremely difficult clinical entity to achieve complete cure. So far, there has been no clear report demonstrating complete cure of prostate cancer with nodular bladder invasion, stage T4 prostate cancer. Case presentation In this case report, the author presents a 55-year-old man with a diagnosis of advanced prostate cancer invading into the bladder wall with pelvic lymph node metastasis (T4N1M0 disease). The patient was treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with whole pelvis (WP) external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT): neo-adjuvant six months plus adjuvant six months ADT. There was no grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity during follow-up. There was no evidence of hematuria, nor rectal bleeding in the follow-up. The patient stays healthy without biochemical failure and without bowel and urinary troubles at six years. Conclusions Along with previous outstanding data of BED ≥ 220 Gy LDR-based radiotherapy for high-risk and very high-risk prostate cancer patents, including pelvic lymph node metastasis, the present report, in which the patient was treated with BED ≥ 220 Gy of high-dose radiotherapy, LDR brachytherapy in combination with WP EBRT may be an optimal treatment for prostate cancer with nodular bladder invasion with lymph node metastasis (T4N1disease).

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

Background Margin negative resection in pancreatic cancer remains the only curative option but is challenging, especially with the retroperitoneal margin. Intraoperative radiation therapy (IORT) can improve rates of local control but requires specially designed facilities and equipment. This retrospective review describes initial results of a novel implantable mesh of uni-directional low dose rate (LDR) Pd-103 sources (sheet) used to deliver a focal margin-directed high-dose boost in patients with concern for close or positive margins. Methods Eleven consecutive patients from a single institution with resectable or borderline resectable pancreatic cancer with concern for positive margins were selected for sheet placement and retrospectively reviewed. Procedural outcomes, including the time to implant the device and complications, and clinical outcomes, including survival and patterns of failure, are reported. A dosimetric comparison of the LDR sheet with hypothetical stereotactic body radiotherapy (SBRT) boost is reported. Results One patient had a resectable disease, and 10 patients had a borderline resectable disease and underwent neoadjuvant treatment. Sheet placement added 15 min to procedural time with no procedural or sheet-related complications. At a median follow up of 13 months, 64% (n = 7) of patients are alive and 55% (n = 6) are disease-free. Compared to a hypothetical SBRT boost, the LDR sheet delivered a negligible dose to kidneys, liver, and spinal cord with a 50% reduction in max dose to the small bowel. Conclusion This is the first report of the use of an implantable uni-directional LDR brachytherapy sheet in patients with resected pancreatic cancer with concern for margin clearance, with no associated toxicity and favorable clinical outcomes.

Background/aim The factors associated with longitudinal changes in health-related quality of life (HRQOL) are unclear. In this study we aimed to evaluate the longitudinal changes and predictors of HRQOL after 125I low-dose-rate brachytherapy (LDB) for localised prostate cancer (PCA). Patients and methods We evaluated 180 patients with localised PCA treated with LDB. The HRQOL was evaluated at 3 weeks before LDB and at 1, 3, 6, 12, 18, 24, 36, and 48 months after LDB using the International Prostate Symptom Score, Medical Outcome Study 8-Items Short Form Health Survey (SF-8), and University of California Los Angeles Prostate Cancer Index (UCLA-PCI). Results All HRQOL scores, except for UCLA-PCI sexual function and SF-8 mental component summary (MCS), were improved to baseline after an early transient deterioration. In contrast, the sexual function did not return to baseline after early deterioration. Meanwhile, the MCS scores showed no significant decline after implantation and trended upward. The prostate V100 and baseline UCLA-PCI sexual function scores predicted a clinically significant decrease in sexual function in the late post-implantation period. Conclusion Most aspects of the HRQOL of PCA patients who underwent LDB improved to baseline. The results that V100 and baseline sexual function were predictors of late post-LDB may provide more accurate information for patients with preserved sexual function before treatment and for their partners.

We aimed to investigate whether gold marker implantation in the tissue surrounding the prostate could accurately monitor setup errors during external beam radiation therapy (EBRT) following low-dose-rate (LDR) brachytherapy. Thirty-eight patients had confirmed intermediate- or high-risk prostate cancer and received EBRT following LDR brachytherapy. In >175 computed tomography imaging sessions, the average values of the weekly setup error during EBRT to the prostate centroid at the time of gold marker matching in the surrounding tissue of the prostate and pelvic bone matching were measured and then compared using the Wilcoxon signed-rank test. Gold marker matching in the surrounding tissue of the prostate estimated setup errors better than those estimated by bone matching (3D displacement = 2.7 ± 2.0 vs 3.8 ± 2.6 mm, P

OBJECTIVES: To compare the dose evaluation parameters between conventional (using loose seed alone) and hybrid (using loose seeds in combination with stranded seeds) low-dose rate brachytherapy for prostate cancer. METHODS: Between 2014 and July 2016, a total of 219 patients who underwent low-dose rate brachytherapy were enrolled in a randomized controlled trial (trial number: UMIN 000012780). Patients were randomized and allocated to two groups (conventional method vs hybrid method). Post-dosimetric parameters (%D90, minimal percentage of the dose received by 90% of the prostate gland; V100, percentage of the prostate volume receiving 100% of the prescribed minimal peripheral dose; V150, percentage of the prostate volume receiving 150% of the prescribed minimal peripheral dose; %UD30, minimal percentage of the dose received by 30% of the urethra; R100, rectal volume [mL] receiving 100% of the prescribed dose) calculated at 1 month after seed implantation by computed tomography scan were compared between the two groups, as well as the post-dosimetric parameters using the planning target volume of the prostate + 5-mm margin. RESULTS: Regarding dose evaluation parameters, the prostate dose (%D90, V100, V150) and the urethral dose (%UD30) were not significantly different between the two groups, whereas V100 (+5-mm margin) and %D90 (+5-mm margin) were significantly higher in the hybrid method group compared with the conventional method group (P

Objectives To evaluate the use of cyclooxygenase-2 inhibitors in patients receiving low-dose-rate brachytherapy for prostate cancer. Methods A total of 310 patients with prostate cancer (cT1c-3aN0M0) who received low-dose-rate brachytherapy between May 2010 and July 2013 were enrolled and allocated to one of the two treatment groups (tamsulosin alone 0.2 mg/day for 6 months vs tamsulosin 0.2 mg/day for 6 months plus celecoxib 200 mg/day for 3 months). The primary end-point was the chronological change in international prostate symptom score, and the number of patients was assessed for the primary end-point. Biochemical recurrence-free, cancer-specific survival and overall survival rates 5 years after the last patient received low-dose-rate brachytherapy were retrospectively examined. Results The median follow-up period after low-dose-rate brachytherapy was 72.0 months (range 3-99 months). A total of 12 (3.9%) patients experienced biochemical recurrence. The biochemical recurrence-free rate in the celecoxib group (5-year biochemical recurrence-free rate 98.5%) was significantly better (log-rank test P = 0.023, 95% confidence interval 0.07-0.63, hazard ratio 0.20) than that in the tamsulosin group (5-year biochemical recurrence-free rate 93.4%). None of the patients died from prostate cancer. However, 14 (4.5%) patients died of other causes. No significant difference was observed in terms of overall survival between the celecoxib and tamsulosin groups. Conclusions The combination of cyclooxygenase-2 inhibitor and low-dose-rate brachytherapy can contribute to a better biochemical control of prostate cancer.

Background As aging is the most significant risk factor for cancer development, long-term prostate cancer (PCa) survivors have an evident risk of developing subsequent primary cancers (SPCs). Radiotherapy itself is an additional risk factor for cancer development and the SPCs appearing beyond 5 years after radiotherapy in the original treatment field can be considered as radiation-induced subsequent primary cancers (RISPCs). Methods During the years 1999-2008, 241 patients with localized PCa who underwent low dose-rate brachytherapy (LDR-BT) with I125 and were followed-up in Kuopio University Hospital, were included in this study. In this study the incidences and types of SPCs and RISPCs with a very long follow-up time after LDR-BT were evaluated. Results During the median follow-up time of 11.4 years, a total of 34 (14.1%) patients developed a metachronous SPC. The most abundant SPCs were lung and colorectal cancers, each diagnosed in six patients (16.7% out of all SPCs). The crude incidence rate of RISPC was 1.7% (n = 4). Half of the SPC cases (50%) were diagnosed during the latter half of the follow-up time as the risk to develop an SPC continued throughout the whole follow-up time with the actuarial 10-year SPC rate of 7.0%. The crude death rates due to metachronous out-of-field SPCs and RISPCs were 50 and 50%, respectively. Conclusion The crude rate of SPC was in line with previously published data and the incidence of RISPC was very low. These results support the role of LDR-BT as a safe treatment option for patients with localized PCa.

Purpose To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer. Methods and Materials The minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the postimplant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the α/β ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity. Results Common dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade ≥ 2 GU toxicity. There was a significant correlation between Grade ≥2 GU toxicity and uBED when the α/β value was 0.5 or 1 Gy and t1/2 was 0.5–2.5 h. An uBED (α/β = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade ≥ 2 GU toxicity according to multivariate analysis. Conclusions We observed a significant correlation of uBED with GU toxicity when α/β was 0.5 or 1.0 Gy and t1/2 was 0.5–2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results.

Background Radical prostatectomy and radiotherapy are standard treatments for localized prostate cancer. When making decisions about treatment, it is important to not only consider medical information such as the patient's age, performance status, and complications, but also the impact on quality of life (QOL) after treatment. Our purpose was to compare health related quality of life (HRQOL) after robot-assisted laparoscopic radical prostatectomy (RARP) versus radiation therapy in Japanese patients with localized prostate cancer retrospectively. Methods Patients with localized prostate cancer receiving RARP or radiotherapy at Tottori University Hospital between October 2010 and December 2014 were enrolled in a retrospective observational study with follow-up for 24 months to December 2016. The Medical Outcome Study 8-Item Short-Form Health Survey was performed before treatment and 1, 3, 6, 12, and 24 months post-treatment. Results Complete responses to the questionnaire were obtained from 154/227 patients receiving RARP, 41/67 patients receiving intensity-modulated radiation therapy, 35/82 patients receiving low dose rate brachytherapy, and 18/28 patients given low dose rate brachytherapy plus external beam radiation therapy. The median physical component summary score of the Medical Outcome Study 8-Item Short-Form Health Survey was significantly lower at 1 month after prostatectomy than radiotherapy, but was similar for both treatments at 3 months, and was significantly higher at 6, 12 and 24 months after prostatectomy. The median mental component summary score was also significantly lower in the prostatectomy group at 1 month, but not from 3 months onwards. Conclusion Our study suggested that HRQOL was inferior at 1 month after RARP, however, recovered at 3 months after RARP and was better than after radiotherapy at 6, 12, and 24 months.

OBJECTIVE To evaluate the long-term oncological, functional and toxicity outcomes of low-dose-rate brachytherapy (LDR-BT) in relation to risk factors and radiation dose in a prospective multicentre cohort. PATIENTS AND METHODS Data of patients from 12 Swiss centres undergoing LDR-BT from September 2004 to March 2018 were prospectively collected. Patients with a follow-up of ≥3 months were analysed. Functional and oncological outcomes were assessed at ~6 weeks, 6 and 12 months after implantation and annually thereafter. LDR-BT was performed with 125 I seeds. Dosimetry was done 6 weeks after implantation based on the European Society for Radiotherapy and Oncology recommendations. The Kaplan-Meier method was used for biochemical recurrence-free survival (BRFS). A prostate-specific antigen (PSA) rise above the PSA nadir + 2 was defined as biochemical failure. Functional outcomes were assessed by urodynamic measurement parameters and questionnaires. RESULTS Of 1580 patients in the database, 1291 (81.7%) were evaluable for therapy outcome. The median (range) follow-up was 37.1 (3.0-141.6) months. Better BRFS was found for Gleason score ≤3+4 (P = 0.03, log-rank test) and initial PSA level of

Purpose:To monitor the outcomes for intermediate-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 200 Gy radiotherapy using low-dose-rate (LDR) brachytherapy., Material and methods:Between 2005 and 2016, a total of 397 patients with intermediate-risk prostate cancer were treated by LDR-based radiotherapy with a BED ≥ 200 Gy. Treatments consisted of LDR brachytherapy alone (177 cases) or LDR and external beam radiotherapy (EBRT) (220 cases). Short-term androgen deprivation therapy (ADT) was used in 186 patients (46.9%). The median follow-up period was 72 months (range 29-165 months). Dosimetric parameters and BED were studied in each case. The numbers of intermediate-risk features were: 163 patients with 1 intermediate-risk feature (41%), 169 patients with 2 intermediate-risk features (43%), and 65 patients with 3 intermediate-risk features (16%). A total of 145 cases were diagnosed as having primary Gleason pattern 4: Gleason score 4 + 3 (36.5%)., Results:Three patients developed biochemical failure, thus providing a 7-year actual biochemical failure-free survival (BFFS) rate of 99.1%. Biochemical failure was observed exclusively in cases with distant metastasis: two cases with lymph node metastasis and one case with bone metastasis, thus yielding a 7-year freedom from clinical failure (FFCF) rate of 99.1%. We observed eight deaths, but there was no death from prostate cancer, thus yielding a 7-year cause-specific survival (CSS) rate of 100%, and an overall survival (OS) rate of 98.4%., Conclusions:This study highlights excellent outcomes for intermediate-risk prostate cancer patients, including unfavorable intermediate-risk cases, treated with BED ≥ 200 Gy radiotherapy using LDR brachytherapy. LDR alone with a BED of 200 Gy may be an optimal treatment for both favorable and unfavorable intermediate-risk prostate cancer patients, although a longer follow-up is mandatory to confirm the present findings.

Highlights • Superior biochemical progression free survival for LDR in combination with EBRT. • On multivariable analysis, HDR and EBRT and Gleason ≥8 predicted for progression. • Low cumulative incidence of ≥grade 3 GU and GI toxicities., Introduction There is evidence to support use of external beam radiotherapy (EBRT) in combination with both low dose rate brachytherapy (LDR–EBRT) and high dose rate brachytherapy (HDR–EBRT) to treat intermediate and high risk prostate cancer. Methods Men with intermediate and high risk prostate cancer treated using LDR–EBRT (treated between 1996 and 2007) and HDR–EBRT (treated between 2007 and 2012) were identified from an institutional database. Multivariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results 116 men were treated with LDR-EBRT and 171 were treated with HDR–EBRT. At 5 years, bPFS was estimated to be 90.5% for the LDR–EBRT cohort and 77.6% for the HDR–EBRT cohort. On multivariable analysis, patients treated with HDR–EBRT were more than twice as likely to experience biochemical progression compared with LDR–EBRT (HR 2.33, 95% CI 1.12–4.07). Patients with Gleason ≥8 disease were more than five times more likely to experience biochemical progression compared with Gleason 6 disease (HR 5.47, 95% CI 1.26–23.64). Cumulative incidence of ≥grade 3 genitourinary and gastrointestinal toxicities for the LDR–EBRT and HDR–EBRT cohorts were 8% versus 4% and 5% versus 1% respectively, although these differences did not reach statistical significance. Conclusion LDR–EBRT may provide more effective PSA control at 5 years compared with HDR–EBRT. Direct comparison of these treatments through randomised trials are recommended to investigate this hypothesis further.

Aims To externally validate a proposed biochemical definition of cure following low dose rate (LDR) brachytherapy for prostate cancer - 4-year post-implant prostate-specific antigen (PSA) ≤0.2 ng/ml - in a UK population, and report the long-term (10- and 15-year) outcomes for patients stratified by National Comprehensive Cancer Network (NCCN) risk groups, through analysis of a large, prospectively collected, single-centre database. Materials and methods All patients treated with LDR brachytherapy for prostate cancer at a single UK centre between 2001 and November 2020 (n = 1142) were eligible; 632 patients met the inclusion criteria for the analysis. The primary end point was disease-free survival (DFS), defined as freedom from clinical, radiological or PSA progression requiring androgen deprivation therapy. Four-year PSA was categorised as ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml. Kaplan-Meier analysis to 15 years was undertaken for each group, and sensitivity and specificity of 4-year PSA as a surrogate for long-term cure were calculated. Kaplan-Meier analysis to 15 years was repeated, stratifying patients by NCCN risk groups. Results The median cohort age was 63 years; the median follow-up was 9.1 years (range 3.5-18.7). In total, 248 patients were available for analysis at year 10, 46 at year 15. Sixty-four patients (10.1%) relapsed during the study period. The 10-year DFS for 4-year PSA categories ≤0.2, >0.2 to ≤0.5, >0.5 to ≤1.0 and >1.0 ng/ml (95% confidence intervals) were 97.5% (95.4-99.6), 89.0% (82.4-96.1), 81.5% (70.5-94.2) and 41.8% (29.7-58.9), respectively. The 10-year DFS results for NCCN low, favourable-intermediate and unfavourable-intermediate risk disease were 93.1% (89.6-96.7), 92.1% (87.6-96.9) and 75.9% (67.8-84.9), respectively. Conclusions Patients with 4-year PSA ≤0.2 ng/ml may be considered cured, and could be discharged to general practitioner follow-up. LDR brachytherapy is an excellent treatment option for patients with low and favourable-intermediate risk prostate cancer, but those with unfavourable-intermediate risk disease should be considered for treatment intensification strategies.

OBJECTIVE Higher quality of postimplant dosimetric evaluation is associated with higher biochemical recurrence-free survival rates after low-dose-rate brachytherapy for localized prostate cancer. Postimplant prostate D90 is a key dosimetric parameter showing the quality of low-dose-rate brachytherapy. In this study, to improve the quality of low-dose-rate brachytherapy for localized prostate cancer, we investigated pre-implant factors affecting the reduction of postimplant prostate D90. METHODS A total of 441 patients underwent low-dose-rate brachytherapy monotherapy and 474 patients underwent low-dose-rate brachytherapy with external beam radiation therapy. Logistic regression analysis was carried out to identify predictive factors for postimplant D90 decline. The cut-off value of the D90 decline was set at 170 Gy and 130 Gy in the low-dose-rate brachytherapy monotherapy group and low-dose-rate brachytherapy with external beam radiation therapy group, respectively. RESULTS On multivariate analysis, neoadjuvant androgen deprivation therapy was identified as an independent predictive factor for the decline of postimplant D90 in both the low-dose-rate brachytherapy monotherapy group (P

INTRODUCTION AND OBJECTIVE:There is currently insufficient evidence on the appropriate surveillance duration after low-dose-rate brachytherapy (LDR) with iodine-125 for localized prostate cancer (P...

OBJECTIVES To report clinical and functional outcomes for patients who have undergone salvage robot-assisted seminal vesicle excision (RA-SVE) for the focal treatment of isolated seminal vesical (SV) recurrence after treatment for prostate cancer by low-dose-rate brachytherapy. PATIENTS AND METHODS Patients with rising prostate-specific antigen (PSA) after low-dose-rate prostate brachytherapy (LDR-PB) underwent multi-parametric magnetic resonance imaging (mp-MRI) of the prostate and 11 C-Choline or 68 Ga-prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) scan, followed by targeted transperineal biopsy of the prostate and SVs. Isolated SV recurrence were identified in 17 (0.38%) LDR-PB patients. These 17 patients were offered RA-SVE. RESULTS The median total operative time was 90 min and blood loss 50 mL with no postoperative transfusions required. The median hospital stay was 1 day. No intra- or postoperative complications were documented. Continence status was unaffected, no patient required urinary pads. Postoperative pathology confirmed SV invasion in all specimens. Surgical margins were positive in seven (41%) patients. All patients had at least one positive imaging study, although three (18%) mp-MRI and five (29%) PET/CT assessments were negative. One (6%) pre-SVE biopsy was also negative but with positive imaging. Salvage SVE failure, defined as three consecutive PSA rises or the need for further treatment, occurred in six patients of whom three had a positive margin. Overall failure-free survival rates were 86%, 67%, and 53% at 1, 2, and 3 years after SVE, respectively. CONCLUSIONS Salvage RA-SVE appears to be a safe focal treatment, with very low morbidity, for patients with localised SV recurrence after LDR-PB. It permits deferral of androgen deprivation therapy in selected patients. Bilateral SVE is mandatory. This surgical option should be considered in patients with isolated prostate cancer recurrence to the SV.

Previous studies have demonstrated excellent overall outcomes in patients who underwent low-dose-rate brachytherapy (LDR-BT) in intermediate-risk, localized prostate cancer (PCa). We thus investigated the appropriate length of time before completing prostate-specific antigen (PSA) monitoring after treatment. Between 2003 and 2014, 710 localized, intermediate-risk PCa patients underwent LDR-BT with or without supplemental external beam radiotherapy (EBRT). Data from 567 of those patients was analyzed in this study. Neoadjuvant hormonal therapy (NHT) was administered to 315 patients (55.6 %) and NHT with adjuvant hormonal therapy (AHT) to 59 patients (10.4 %), as per the protocol of a prospective randomized controlled trial (SHIP0804). We stratified patients by posttreatment PSA levels at specific times and assessed the factors for association with biochemical recurrence (BCR) and for clinical progression (CP). The median follow-up was 109 months (range, 60-205 months). Of 529 patients who were BCR-free at 3 years after treatment, 56 subsequently developed BCR, and 47 developed CP. PSA at 3 and 5 years after treatment were significantly correlated with long-term oncological outcomes. No patients with 5-year PSA levels ≤0.1 ng/mL subsequently developed BCR or CP. Discontinuation of PSA monitoring could be discussed with patients with intermediate-risk PCa as a reasonable option if PSA levels remain ≤0.1 ng/mL at 5 years after LDR-BT, either alone or with other combined modalities, as subsequent recurrences are quite rare.

OBJECTIVE To report the long-term clinical outcomes of low-risk (LR) and intermediate-risk (IR) prostate cancer patients treated with low-dose-rate brachytherapy (LDR-BT) and external beam radiation therapy (EBRT). PATIENTS AND METHODS Men with biopsy-proven low- and intermediate-risk prostate cancer received EBRT and LDR-BT in an Asian academic center from 2000 to 2019 were reviewed. Kaplan-Meier survival analysis was performed to compare biochemical failure-free survival (bFFS) and overall survival (OS) between LDR and EBRT in the low- and intermediate-risk cohorts. RESULTS 642 patients (521 EBRT and 121 LDR-BT) with low- and intermediate-risk prostate cancer were included for analysis. In the intermediate-risk group, 5- and 10-year bFFS was 96%, 89% and 86%, 61% for LDR-BT and EBRT, respectively. LDR-BT was associated with a statistically significant improvement of bFFS in the intermediate-risk cohort (HR 2.7, p = 0.02). In the low-risk cohort, no difference of bFFS was found between LDR-BT and EBRT (HR 1.9, p = 0.08). Hormone therapy was more common in EBRT than LDR-BT for intermediate-risk group (71% versus 44%, p

PurposeWe report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up.Methods and materialsEligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen

Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques.Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale.Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%-75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients.These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

This study aimed to evaluate the oncological outcomes and post-implantation complications of the concurrent androgen deprivation therapy (ADT) with I-125 low-dose-rate (LDR)-prostate brachytherapy (sparse implantation technique: SIT) in comparison with the conventional non-ADT using whole gland brachytherapy (CWT). 302 localized prostate cancer (PCa) patients were treated with CWT (implantation dose: 145 Gy) and 215 patients were treated with SIT, which applied reduced implantation dose of 123.5 Gy. SIT group had ADT consisting of bicalutamide 50 mg/day plus 3-month depot (11.25 mg) of leuprolide acetate subcutaneously on the post-implantation day-0. Post-implantation complications and biochemical-recurrence-free-survival (BCRS) were compared between the two groups. After ADT, SIT group had 40.9% patients (40.9%) with prostate volume reduction between 20–30%. At 3-months post-implantation, SIT group presented significantly better IPSS than CWT group (p = 0.038). Both groups showed decrease in IIEF-5 score at 3-months post-implantation, but ST group showed significantly better mean IIEF-5 scores (13.5) than the CWT group (11.1) (p = 0.045). For 3-months post-implantation dosimetry, both groups showed no significant differences regarding D90 (CWT 156 Gy vs. SIT 152 Gy). CWT group had 3 patients with rectal toxicity ≥radiation therapy oncology group (RTOG) grade 2 and 1 patient with urinary toxicity ≥RTOG grade 2 whereas SIT group had no patient with urinary or rectal toxicity ≥RTOG grade 2. Kaplan-Meier analyses showed no significant differences regarding PCSS were observed between the two groups (p = 0.350). The SIT group showed compatible oncological outcomes to the CWT and relatively smaller number of post-implantation complications within low- and intermediate-risk PCa patients.

Objective To examine the effect of permanent salvage brachytherapy in prostate cancer patients suffering recurrence after three-dimensional conformal external beam radiotherapy. Methods The ultra-focal (target lesion alone), hemi-lobe (within a hemi-lobe) or focused whole-gland (focusing on the lesion, but extending into the whole gland) pattern was selected based on the Gleason score for the targeted biopsy, the numbers of positive cores in the targeted and systematic biopsies, and the locations of the positive cores. Novel dosimetry criteria derived from three-dimensional cancer mapping, which was based on targeted magnetic resonance imaging/transrectal ultrasound fusion biopsies, were used in these cases. Results Permanent salvage brachytherapy was carried out in 13 patients who suffered prostate-specific antigen failure (prostate-specific antigen 2.1-6.8 ng/mL; age range 57-75 years; Gleason score ≤7 [n = 10], Gleason score ≥8 [n = 2] and Gleason score not available [n = 1]) since 2012. The targeted biopsy showed a single focus in three patients. The ultra-focal, hemi-lobe and focused whole-gland patterns were chosen in three, five and five patients, respectively. During the follow-up period (median duration 48 months), prostate-specific antigen failure occurred in zero of three, one of five and three of five of the patients treated with the ultra-focal, hemi-lobe and focused whole-gland patterns, respectively. The 4-year biochemical recurrence-free survival rate was 74%. No grade 3-4 adverse intestinal or urological events occurred. Conclusions Targeted fusion biopsy-based three-dimensional cancer mapping should be used for permanent salvage brachytherapy treatment planning to reduce the incidence of treatment-related adverse events while maintaining good oncological outcomes.

OBJECTIVES The aim of the present study was to report on our early experience with hydrogel spacer (SpaceOAR) placement in combination with iodine-125 low-dose-rate brachytherapy for prostate cancer. METHODS From April 2018, SpaceOAR hydrogel spacer was placed in 100 consecutive patients undergoing iodine-125 low-dose-rate brachytherapy. Complications and the status of the placement were evaluated. Deformation of the prostate by the spacer was examined measuring prostate diameters and evaluating the change from preoperative status. The position of the prostate was similarly examined by evaluating the change in distance between the pubic symphysis and the prostate. Post-plan dosimetric data were compared with 200 patients treated without a spacer. RESULTS No complications were found during either the intraoperative or perioperative periods. The mean displacement distance of 11.64 mm was created, the mean value before spacer placement was 0.28 mm (P

Purpose The goal of this study was to evaluate the effect of cyclooxygenase-2 (COX-2) inhibitors on quality of life (QoL) of patients undergoing low-dose-rate (LDR) brachytherapy. Material and methods A total of 310 patients with prostate cancer who had undergone LDR brachytherapy were enrolled. The patients were randomized (1 : 1) to the monotherapy group (tamsulosin alone: 0.2 mg/day, n = 156) and the combination group (tamsulosin: 0.2 mg/day plus celecoxib: 200 mg/day, n = 154) without placebo. Using the expanded prostate cancer index composite (EPIC) and medical outcomes study 8-item short form health survey (SF-8) questionnaire, QoL was evaluated at baseline and at 1, 3, 6, and 12 months after seed implantation. Results The mean changes in scores from baseline to 1 and 3 months after seed implantation for the urinary (1M: -10.5, 3M: -10.9) and bowel (1M: -2.4, 3M: -4.2) domains of EPIC in the combination group were not significantly different from those (urinary 1M: -11.0, 3M: -11.4, bowel 1M: -2.3, 3M: -4.6) in the monotherapy group. The mean changes in scores from baseline to 1 and 3 months after seed implantation for the physical component summary (1M: 0.009, 3M: -0.32) and mental component summary (1M: 0.41, 3M: 0.36) of SF-8 in the combination group were not significantly different from those (physical component 1M: -0.89, 3M: -0.22, mental component 1M: 1.3, 3M: 1.1) in the monotherapy group. Conclusions Combination treatment with celecoxib and tamsulosin during the peri-operative period is not warranted for improving QoL in patients undergoing LDR brachytherapy.

Purpose To compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial. Methods and Materials Men with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples t test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted P value of ≤.05 was considered significant. Results LDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively; P = .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively; P = .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS (P = .003) and EPIC urinary irritative scores (P = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months; P = .028). Conclusions HDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.

The history of prostate brachytherapy has passed one century. In 1983, modern low-dose-rate prostate brachytherapy using a transrectal ultrasound-guided procedure was introduced. In the early 1990s, low-dose-rate brachytherapy was introduced and rapidly spread across the USA due to its excellent oncological control, cost-effectiveness and technically easy procedure. Since low-dose-rate brachytherapy was introduced in Japan (2003), over 15 years have passed. More than 43 000 patients have undergone low-dose-rate brachytherapy. Japanese urologists and radiation oncologists are on course with leading brachytherapists in the USA. A nationwide prospective cohort study, J-POPS, was initiated in 2005. The J-POPS group also provides educational programs including an annual novel training course in low-dose-rate brachytherapy to familiarize urologists, radiation oncologists and pathologists with the procedure. Important information on Japanese patients has accumulated, especially by the J-POPS study group. The Japanese investigators reported excellent oncological outcomes of low-dose-rate brachytherapy, showing equivalent or superior efficacy to surgery in low- to intermediate-risk patients, and superior efficacy in high-risk patients using the surgery biochemical recurrence definition (prostate-specific antigen cut-off value of 0.2 ng/mL). Two randomized controlled studies (SHIP study: intermediate risk, and TRIP study: high risk) carried out by the J-POPS group are ongoing, and an additional follow-up study (J-POPS 2 study) has been started to evaluate survival outcomes over longer follow-up periods. Low-dose-rate brachytherapy is expected to provide a survival benefit, which must be confirmed by further studies with longer follow-up periods in the future.

Recurrence of prostate cancer after initial treatment with radiation therapy (RT) is highly dependent on pretreatment risk group and unfortunately, a proportion of patients fail primary treatment. The treatment of recurrence after primary radiation is rapidly changing with advances in imaging and it is important to distinguish those with a local failure from those with distant failure. If disease remains locally confined, salvage treatment with a variety of techniques can still provide a potential cure. Patients with distant failure are often treated with androgen deprivation, or in those with a shorter life expectancy, conservative management. In patients with a higher burden of metastatic disease, there is emerging evidence that chemotherapy and advanced androgen therapy can improve survival. We review the relevant literature on available salvage treatment options and appropriate patient selection for patients with recurrent prostate cancer after RT. We report on the efficacy and adverse effects of the currently available local salvage modalities including salvage radical prostatectomy, high dose rate and low dose rate brachytherapy, cryotherapy, high intensity focused ultrasound, and stereotactic body RT. We additionally discuss diagnosis of oligometastatic disease on imaging and current approaches to treatment with either radiation or surgery. While a full review of chemotherapy and advanced androgen therapies is beyond the scope of this article we briefly discuss their use in the treatment of newly diagnosed recurrence after radiation.

Purpose The purpose of this study was to evaluate the incidence of late severe (≥Grade 3) urinary toxicity and the long-term efficacy after low-dose-rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa). Methods and Materials During the years 1999–2008, 241 patients with PCa who underwent LDR-BT with I 125 and were followed up in Kuopio University Hospital were included to this analysis. The incidence of late severe (Grade 3) urinary toxicity and the long-term efficacy results were analyzed. Results All D'Amico risk groups were represented, as 58.9%, 35.3%, and 5.8% of the patients were classified as low-, intermediate-, and high-risk patients, respectively. With a median followup of 11.4 years after implantation, the incidence of severe urinary toxicity increased throughout the followup period. The risk of Grade 3 urinary toxicity was highest among patients with higher Gleason scores ( p = 0.016) and higher initial urine residual volumes ( p = 0.017) and the cumulative incidence of severe urinary toxicity was 10.0%. The crude rate for transurethral prostatic resection was 5.8%. The relapse-free survival, the cause-specific survival, and the overall survival were 79.3%, 95.0%, and 66.4%, respectively. Conclusions The treatment was well tolerated as 90% of patients avoided any Grade 3 urinary toxicity. LDR-BT for localized PCa achieved high and durable efficacy. These results support the role of LDR-BT monotherapy as one of the valid primary treatment options for low-risk and favorable intermediate-risk patients.

OBJECTIVES To evaluate the oncological and functional outcomes of salvage high-intensity focused ultrasound (S-HIFU) for locally recurrent prostate cancer after low-dose-rate (LDR) brachytherapy. PATIENTS AND METHODS Clinical phase II studies (2003-2015) included 50 consecutive patients with post-brachytherapy local recurrence treated by S-HIFU. S-HIFU was performed with post-external beam radiotherapy (EBRT) parameters and, since 2008, with specific post-brachytherapy parameters. Treatments were whole-gland ablation and, since 2009, hemi-ablation in cases of unilateral prostate cancer. The primary objective was to assess oncological outcomes: treatment failure-free survival, progression-free survival (PFS), overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) rates. The secondary objective was to evaluate adverse events, continence, and erectile function. Kaplan-Meier analysis estimated oncological outcomes. RESULTS In all, 13 patients were treated with post-EBRT parameters, 37 with post-brachytherapy parameters, 35 with whole-gland treatment, and 15 with hemi-ablation. The median follow-up was 4.6 years. After S-HIFU, the median prostate-specific antigen level was 0.3 ng/mL. At 6 years, treatment failure-free survival, PFS, OS, CSS, and MFS rates were 41%, 45%, 93%, 98%, and 80%, respectively. Post-brachytherapy compared with post-EBRT parameters reduced Grade 2-3 incontinence (34% vs 62%, P = 0.015). Incontinence, bladder outlet obstruction and Grade ≥III complications were significantly reduced with hemi-ablation compared with whole-gland treatment (14% vs 54%, P

PURPOSE:To compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) and low-dose-ratebrachytherapy (LDR-BT) as monotherapy for localized prostate cancer of low and intermediate risks progression. METHODS AND MATERIALS: The study included 165 patients with localized prostate cancer in low and intermediate progression risk groups. We compared 65 patients treated with HDR-BT and 100 patients with LDR-BT as monotherapy. LDR-BT treated advanced disease with more hormonal therapy than HDR-BT. All patients were in low and intermediate risk groups for prostate cancer progression. HDR-BT as monotherapy was delivered in 2 fractions of 15 Gy, two weeks apart. LDR-BT was performed in a standard mode of 145 Gy. The median observation was 32 months. All patients gave written informed consent. RESULTS: Overall biochemical free survival rate (BFSR) is 95,8%. There are 7 people having a growing prostatic specific antigen (PSA) while the case follow-up (in the group HDR-BT - 2 patients, LDR - 5 patients). Two recurrence cases with metastases in lymph nodes and bones were brought out as a result of 68Ga-PSMA PET examination in the group of HDR-BT. In 4 cases out of 5 LDR-BT, a local recurrence was detected (p=0,085). All cases of relapse were found in patients at intermediate risk (p = 0,041). LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade >2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Accumulated incidence of late grade >2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. CONCLUSION: HDR-BT monotherapy showed an equivalent outcome to that of LDR-BT for low and intermediate risk patients. LDR-BT showed equivalent incidence of grade >2 late GU toxicities and higher grade >2 acute GU toxicity as that of HDR-BT as a monotherapy.

Background To compare the outcome of high-dose-rate interstitial brachytherapy (HDR-BT) monotherapy and low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy (EBRT) for localized prostate cancer. Methods and materials We compared 352 patients treated with HDR-BT as monotherapy (median follow-up time 84 months, NCCN risk classification; low: intermediate: high = 28:145:179) and 486 patients with LDR-BT with or without EBRT (90 months, 194:254:38). HDR-BT treated advanced disease with more hormonal therapy than LDR-BT. LDR-BT excluded patients with T3b–T4 tumor and initial PSA >50 ng/ml. Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. Results The actuarial 5-year biochemical failure-free survival rates (bNED) were 92.9% and 95.6% (p = 0.25) in the HDR-BT and LDR-BT groups, respectively, and it was 100% and 97.3% (p = 0.99) in the low-risk, 95.6% and 94.3% (p = 0.19) in the intermediate, 89.6% and 94.9% (p = 0.26) in the high-risk groups, and 93.1% and 94.9% (p = 0.98) in selected high-risk group excluding T3b-4 and initial PSA ≥50. IPTW correction also indicated no difference in bNED between LDR-BT and HDR-BT groups. LDR-BT showed a higher incidence of genitourinary (GU) toxicity grade ≥2 than that of HDR-BT in the acute phase and grade 1 toxicity in late phase. Acute GU toxicity grade ≥1 predicted late GU toxicity grade ≥2. External beam radiotherapy plus LDR-BT elevated GI toxicity than LDR-BT only group. Accumulated incidence of late grade ≥2 GU and GU toxicity was equivalent between HDR-BT and LDR-BT. No grade 4 or 5 toxicities were detected in either modality. Conclusion HDR-BT monotherapy showed an equivalent outcome to that of LDR-BT with or without EBRT for low-, intermediate- and selected high-risk patients. LDR-BT showed equivalent incidence of grade ≥2 late GI and GU toxicities and higher grade ≥2 acute GU toxicity as that of HDR-BT as a monotherapy.

Background: To evaluate the occurrence of erectile dysfunction at 3 years (3yED) after prostate brachytherapy (BT) and to predict 3yED after treatment based on patients and treatments characteristi...

Background We describe two patients who underwent low-dose-rate prostate brachytherapy after embolization for pelvic arteriovenous malformation. Case presentation Case 1: A 76-year-old man was referred for definitive treatment of intermediate-risk prostate cancer (prostate-specific antigen 8.667 ng/mL, cT2aN0M0, Gleason score 3 + 4 = 7). We planned low-dose-rate brachytherapy. However, magnetic resonance imaging and computed tomography demonstrated a large pelvic arteriovenous malformation. We performed embolization of the arteriovenous malformation before initiating treatment to lower the risk of rupture of the arteriovenous malformation during low-dose-rate brachytherapy. Case 2: A 69-year-old man was referred for the definitive treatment of high-risk prostate cancer (prostate-specific antigen 5.81 ng/mL, cT2aN0M0, Gleason score 4 + 4 = 8) with a pelvic arteriovenous malformation. Similar to Case 1, we performed embolization of the arteriovenous malformation before initiating treatment. In both cases, low-dose-rate brachytherapy could be performed without complications. Conclusions Low-dose-rate brachytherapy after transcatheter embolization of pelvic arteriovenous malformations can safely and effectively treat localized prostate cancer with pelvic arteriovenous malformations.

Purpose To study the feasibility of hyaluronic acid (HA) injection to increase the distance between skin and radioactive sources, and dose reduction of skin during low-dose-rate (LDR) brachytherapy. Material and methods: A total of 11 patients with subdermal malignant tumors were enrolled in this study. HA was injected after I-125 seed implantation, and dosimetric parameters were calculated by a brachytherapy treatment planning system (BTPS). The distance of the new space between radioactive sources and skin was measured on computed tomography (CT) and magnetic resonance imaging (MRI). Clinical signs were observed and followed up for every patient. Results After HA injection, the average of newly generated maximum distance was 1.0 cm along the entire length of the tumor. The D90 and V100 did not significantly change for tumors before or after injection (p = 0.39, p = 0.50, respectively). The maximum dose to a relatively small volume (0.1 cc) of the skin (OAR-Max) decreased from 100.66 Gy to 61.20 Gy (p < 0.05), and the mean skin dose (OAR-Mean) decreased from 49.20 Gy to 17.27 Gy (p < 0.05) after injection. On follow-up CT and MRI, HA was quite stable in shape and position for nearly 6 months. Conclusions Our study results showed that an additional 1.0 cm distance between the radioactive source and skin could be induced by HA injection in patients with subdermal tumor, and this distance could significantly decrease the skin dose in LDR brachytherapy. In addition, no obvious toxicity and side effects were produced by HA injection. Therefore, hyaluronic acid injection is a safe and effective technique.

Background Few studies have assessed hydrogel spacer shrinkage during external-beam radiation therapy following brachytherapy for localized high-risk prostate cancer. This case presentation evaluated the changes in hydrogel spacer appearance by magnetic resonance imaging during external-beam radiation therapy after brachytherapy for prostate cancer and analyzed the effect of this shrinkage on the dose distribution in four cases. Case presentation In all cases, we implanted 125I sources using a modified peripheral loading pattern for seed placement. The prescribed dose for each implant was 110 Gy. After delivering the sources, a hydrogel spacer was injected. All cases underwent external-beam radiation therapy approximately 1–2 months after brachytherapy. The prescribed dose of external-beam radiation therapy was 45 Gy in 1.8-Gy fractions. Magnetic resonance imaging was performed for evaluation on the day following seed implantation (baseline), at external-beam radiation therapy planning, and during external-beam radiation therapy. The median hydrogel spacer volume was 16.2 (range 10.9–17.7) cc at baseline, 14.4 (range, 9.4–16.1) cc at external-beam radiation therapy planning, and 7.1 (range, 2.0–11.4) cc during external-beam radiation therapy. The hydrogel spacer volume during external-beam radiation therapy was significantly lower than that at external-beam radiation therapy planning. The rectum V60–80 (rectal volume receiving at least 60–80% of the prescribed dose of external-beam radiation therapy) during external-beam radiation therapy was significantly higher than that at external-beam radiation therapy planning. Conclusions The potential reduction in hydrogel spacer size during external-beam radiation therapy following brachytherapy can lead to unexpected irradiation to the rectum. This case presentation would be helpful for similar cases.

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