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Abstract We aimed to retrospectively review outcomes in patients with high-risk prostate cancer and a Gleason score ≤ 6 following modern radiotherapy. We analyzed the outcomes of 1374 patients who had undergone modern radiotherapy, comprising a high-risk low grade [HRLG] group (Gleason score ≤ 6; n = 94) and a high-risk high grade [HRHG] group (Gleason score ≥ 7, n = 1125). We included 955 patients who received brachytherapy with or without external beam radio-therapy (EBRT) and 264 who received modern EBRT (intensity-modulated radiotherapy [IMRT] or stereotactic body radiotherapy [SBRT]). At a median follow-up of 60 (2–177) months, actuarial 5-year biochemical failure-free survival rates were 97.8 and 91.8% (p = 0.017), respectively. The frequency of clinical failure in the HRLG group was less than that in the HRHG group (0% vs 5.4%, p = 0.012). The HRLG group had a better 5-year distant metastasis-free survival than the HRHG group (100% vs 96.0%, p = 0.035). As the HRLG group exhibited no clinical failure and better outcomes than the HRHG group, the HRLG group might potentially be classified as a lower-risk group.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachytherapy has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision making regarding radiological parameters by radiation oncologists. The combined use of LDR brachytherapy with other therapeutic modalities, such as external beam radiation and androgen deprivation therapy, for the clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology departments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development.

Over a century ago, low-dose-rate (LDR) brachytherapy was introduced to treat prostate cancer (PCa). Since then, it has been widely applied worldwide, including in East Asia. LDR brachytherapy has been performed in 88 institutes in Japan. Beneficial clinical outcomes of LDR brachytherapy for intermediate-to-high-risk PCa have been demonstrated in large clinical trials. These clinical outcomes were achieved through advances in methods, such as urological precise needle puncture and seed placement, and the quantitative decision making regarding radiological parameters by radiation oncologists. The combined use of LDR brachytherapy with other therapeutic modalities, such as external beam radiation and androgen deprivation therapy, for the clinical risk classification of PCa has led to better anticancer treatment efficacy. In this study, we summarized basic LDR brachytherapy findings that should remain unchanged and be passed down in urology departments. We also discussed the applications of LDR brachytherapy for PCa in various clinical settings, including focal and salvage therapies. In addition, we highlighted technologies associated with brachytherapy that are under development. [ABSTRACT FROM AUTHOR]

In conducting dosimetric assays of seed sources containing iodine-125 (125I), several major guidelines require the medical physicist to verify the source strength before patient treatment. Japanese guidelines do not mandate dosimetric assays at medical facilities, but since 2017, three incidents have occurred in Japan wherein seeds with incorrect strengths were delivered to medical facilities. Therefore, this study aimed to survey the current situation and any barriers to conducting the dosimetric assay of iodine-125 seeds at medical facilities in Japan. We conducted a questionnaire-based survey from December 2020 to April 2021, to examine whether seed assay and verification of the number of seeds delivered were being performed. We found that only 9 facilities (16%) performed seed assay and 28 (52%) verified the number of seeds. None of the facilities used an assay method that ensured traceability. The reasons for not performing an assay were divided into two categories: lack of resources and legal issues. Lack of resources included lack of instruments, lack of knowledge of assay methods, shorthand, or all of the above, whereas legal issues included the inability to resterilize iodine-125 seeds distributed in Japan and/or purchase seeds dedicated to the assay. Dosimetric assays, including simple methods, are effective in detecting calibration date errors and non-radioactive seeds. The study findings suggest that familiarization of medical personnel with these assay methods and investigation of the associated costs of labor and equipment should be recommended, as these measures will lead to medical reimbursement for quality assurance. [ABSTRACT FROM AUTHOR]

Around 40 years have passed since a modern low-dose-rate (LDR) brachytherapy for prostate cancer was introduced. LDR brachytherapy has become one of the definitive treatment options besides radical prostatectomy (RP) and external beam radiation therapy (EBRT). LDR brachytherapy has several advantages over EBRT such as a higher prescribed dose to the prostate gland while avoiding unnecessary irradiation of organs at risk, a precipitous dose gradient, a brief treatment time, and a short hospital stay. Previous reports revealed that the long-term oncologic outcomes of LDR brachytherapy are superior to those of EBRT. The oncologic outcomes of low- to intermediate-risk patients are equivalent to those of RP using the recurrence definition of surgery of prostate specific antigen (PSA) >0.2 ng/mL, while the oncologic outcomes of LDR brachytherapy as tri-modality (combined EBRT and androgen deprivation therapy) for high-risk patients is superior to that of RP using the recurrence definition of surgery. In respect of toxicity, urinary disorders such as urgency and frequency are often observed after the acute phase of treatment, but these events usually resolve, while the quality of life of urinary continence is well preserved for a long time. Erectile function decreases yearly, but is relatively preserved compared to RP. In conclusion, the most noteworthy strength of LDR brachytherapy for low- to intermediate-risk patients is the “brief treatment time” that provides long recurrence-free survival, while that for high-risk patients who received LDR brachytherapy (tri-modality) is “excellent disease control.”

ContextManagement of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.ObjectiveTo quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.Evidence acquisitionWe performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.Evidence synthesisA total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p

Abstract Background This study aims to compare the clinical outcomes after performing radical prostatectomy (RP) or low-dose-rate brachytherapy (LDR) for patients with intermediate-risk prostate cancer (IRPC). Methods We performed a retrospective analysis on 361 IRPC patients who underwent treatment in Peking Union Medical College Hospital from January 2014 to August 2021, of which 160 underwent RP and 201 underwent Iodine-125 LDR. Patients were followed in clinic monthly during the first three months and at three-month intervals thereafter. Univariate and multivariate regression analyses were conducted to predict biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), cancer-specific survival (CSS), and overall survival (OS). Biochemical recurrence was defined using the Phoenix definition for LDR and the surgical definition for RP. The log-rank test was applied to compare bRFS between the two modalities, and Cox regression analysis was performed to identify factors associated with bRFS. Results Median follow-up was 54 months for RP and 69 months for LDR. According to log-rank test, the differences of 5-year bRFS (70.2% vs 83.2%, P = 0.003) and 8-year bRFS (63.1% vs 68.9%, P 50% (P

Background: To explore correlations between the clinical attributes of secondary bladder cancer and brachytherapy, we retrospectively reviewed our institutional database on patients with localized prostate cancer who underwent low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy (HDR-BT) with or without external beam radiation therapy (EBRT) or radical prostatectomy (RP). Methods: From October 2003 to December 2014, 2551 patients with localized prostate cancer were treated at our institution. Of these, data on 2163 were available (LDR-BT alone: n = 953; LDR-TB with EBRT: n = 181; HDR-BT with EBRT: n = 283; RP without EBRT: n = 746). The times of secondary bladder cancer development subsequent to radical treatment, and their clinical characteristics, were studied. Results: Age-adjusted Cox's regression analyses indicated that brachytherapy did not significantly impact the incidence of secondary bladder cancer. However, the pathological characteristics of such cancer differed between patients treated via brachytherapy and RP without EBRT; invasive bladder cancer was more common in such patients. Conclusion: The risk for secondary bladder cancer was not significantly increased after brachytherapy compared to non-irradiation therapy. However, brachytherapy patients exhibited a higher incidence of invasive bladder cancer. Therefore, meticulous follow-up is crucial for early detection and treatment of bladder cancer in such patients. [ABSTRACT FROM AUTHOR]

We aimed to determine whether biochemical recurrence-free survival (BRFS) of patients with prostate cancer (PCa) who received low-dose-rate brachytherapy (LDR-BT) differed according to the definition of biochemical recurrence (BCR) after radical prostatectomy (RP) and the definition given by the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). We reviewed the clinical records of 476 consecutive patients with PCa who received LDR-BT at the Gifu University Hospital. The primary endpoint of this study was the difference in BRFS between the two aforementioned definitions. When the follow-up period ended, 74 (15.5%) and 20 (4.2%) patients had BCR according to the RP and J-POPS definitions, respectively. The 5-year BRFS rates were 85.0% and 96.9% for the RP and J-POPS definitions, respectively (p < 0.005). According to the RP definition, the 5-year BRFS rates were 80.6% in the group aged p = 0.050). According to the J-POPS definition, the 5-year BRFS rates were 94.1% and 97.8% in the groups aged p = 0.005). The definition of recurrence in LDR-BT may need to be reconsidered.

Background: To compare chronological changes in lower urinary tract symptoms (LUTS) after low-dose-rate prostate extended-release therapy (LDR-BT) using the overactive bladder symptom score (OABSS) in patients aged ≥ 75 years (elderly group) versus those aged < 75 years (control group). Materials and Methods: Patients with prostate cancer who underwent LDR-BT at Gifu University Hospital were included in this study. The International Prostate Symptom Score (IPSS), OABSS, and quality of life-based on urinary symptoms (IPSS-QOL) were evaluated before and after LDR-BT. We compared chronological changes in IPSS, OABSS, and IPSS-QOL in the elderly group with those in the control group and assessed the association between the resolution of OABSS and clinicopathological covariates. Results: A total of 484 patients were enrolled in this study. In the elderly group, the total IPSS, OABSS, and frequency scores increased at 1 month postoperatively, whereas the control group showed an increase at 3 months postoperatively. Multivariate analysis identified changes from baseline to the maximum OABSS and pre-treatment OABSS as significant predictors of delayed resolution of OABSS after LDR-BT. Conclusions: Changes in pre-treatment OABSS and pre- and post-LDR-BT OABSS values were independent predictors of delayed resolution of OABSS; however, no correlation was found with age. [ABSTRACT FROM AUTHOR]

Background: This study aims to compare the clinical outcomes after performing radical prostatectomy (RP) or low-dose-rate brachytherapy (LDR) for patients with intermediate-risk prostate cancer (IRPC). Methods: We performed a retrospective analysis on 361 IRPC patients who underwent treatment in Peking Union Medical College Hospital from January 2014 to August 2021, of which 160 underwent RP and 201 underwent Iodine-125 LDR. Patients were followed in clinic monthly during the first three months and at three-month intervals thereafter. Univariate and multivariate regression analyses were conducted to predict biochemical relapse-free survival (bRFS), clinical relapse-free survival (cRFS), cancer-specific survival (CSS), and overall survival (OS). Biochemical recurrence was defined using the Phoenix definition for LDR and the surgical definition for RP. The log-rank test was applied to compare bRFS between the two modalities, and Cox regression analysis was performed to identify factors associated with bRFS. Results: Median follow-up was 54 months for RP and 69 months for LDR. According to log-rank test, the differences of 5-year bRFS (70.2% vs 83.2%, P = 0.003) and 8-year bRFS (63.1% vs 68.9%, P < 0.001) between RP and LDR groups were statistically significant. Our results also indicated that there was no significant difference in terms of cRFS, CSS, or OS between the two groups. With multivariate analysis of the entire cohort, prostate volume ≤ 30 ml (P < 0.001), positive margin (P < 0.001), and percentage positive biopsy cores > 50% (P < 0.001) were independent factors suggestive of worse bRFS. Conclusions: LDR is a reasonable treatment option for IRPC patients, yielding improved bRFS and equivalent rates of cRFS, CSS and OS when compared with RP. [ABSTRACT FROM AUTHOR]

Background: Although brachytherapy is a standard treatment option for patients with high-risk prostate cancer, only a few studies have compared low-dose-rate brachytherapy (LDR-BT) and high-dose-rate brachytherapy (HDR-BT). We applied propensity score-based inverse probability treatment weighting (IPTW) to compare oncological outcomes for LDR-BT and HDR-BT. Methods: We retrospectively assessed prognosis in 392 patients with high-risk localized prostate cancer who had undergone brachytherapy plus external beam radiation. IPTW was applied to adjust the Kaplan–Meier survival analyses and Cox proportional hazards regression analyses, with the goal of minimizing bias from patient background. Results: The IPTW-adjusted Kaplan–Meier survival analyses showed no statistically significant differences for time to biochemical recurrence, clinical progression, castration-resistant prostate cancer, or death from any cause. The IPTW-adjusted Cox regression analyses also showed that the modality of brachytherapy was not an independent factor in these oncological outcomes. Notably, the two groups differed regarding complications; LDR-BT was associated with a higher rate of acute grade ≥ 2 GU toxicity, and late grade 3 toxicity was noted only in HDR-BT. Conclusion: Our analysis of long-term outcomes in patients with high-risk localized prostate cancer shows no significant differences in oncological outcomes between LDR-BT and HDR-BT, but some differences in toxicity, and offers patients and clinicians useful information in deciding management strategies for high-risk localized prostate cancer. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to investigate chronological changes of lower urinary tract symptoms (LUTS) in patients with prostate cancer who underwent low-dose-rate brachytherapy (LDR-BT) followed by the insertion of SpaceOAR® system (SpaceOAR). Methods: In this retrospective study, 483 patients with localized prostate cancer underwent LDR-BT at the Gifu University Hospital between August 2004 and December 2020. SpaceOAR was inserted in 30 patients after LDR-BT (SpaceOAR group), and 453 patients received LDR-BT alone (non-SpaceOAR group). The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), quality of life due to urinary symptoms (IPSS-QOL), and uroflowmetry (UFM), including maximum flow rate (Qmax), voided volume, and post-voided residual urine (PVR), were evaluated before LDR-BT, and at 1, 3, 6, 9, and 12 months after LDR-BT. The outcomes were chronological changes in IPSS, OABSS, and IPSS-QOL compared to pretreatment values and those of covariates in relation to UFM. Results: The IPSS, OABSS, IPSS-QOL, Qmax, and voided volume were not significantly associated with either group. According to the PVR interaction effect, the insertion of SpaceOAR was significantly affected by chronological changes in PVR (P = 0.001). Three months after LDR-BT, PVR in the SpaceOAR group was significantly higher than that in the non-SpaceOAR group (49.8 mL vs. 30.5 mL; P = 0.002). Conclusion: SpaceOAR use may temporally increase PVR; however, IPSS, OABSS, IPSS-QOL, Qmax, and voided volume were not significantly associated with LUTS before and after LDR-BT. The combination of LDR-BT and SpaceOAR may be acceptable for treating patients with prostate cancer regarding the chronological changes in LUTS after brachytherapy.

We aimed to determine whether biochemical recurrence-free survival (BRFS) of patients with prostate cancer (PCa) who received low-dose-rate brachytherapy (LDR-BT) differed according to the definition of biochemical recurrence (BCR) after radical prostatectomy (RP) and the definition given by the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). We reviewed the clinical records of 476 consecutive patients with PCa who received LDR-BT at the Gifu University Hospital. The primary endpoint of this study was the difference in BRFS between the two aforementioned definitions. When the follow-up period ended, 74 (15.5%) and 20 (4.2%) patients had BCR according to the RP and J-POPS definitions, respectively. The 5-year BRFS rates were 85.0% and 96.9% for the RP and J-POPS definitions, respectively (p < 0.005). According to the RP definition, the 5-year BRFS rates were 80.6% in the group aged <63 years and 86.6% in those aged ≥63 years (p = 0.050). According to the J-POPS definition, the 5-year BRFS rates were 94.1% and 97.8% in the groups aged <63 years and ≥63 years, respectively (p = 0.005). The definition of recurrence in LDR-BT may need to be reconsidered. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate prognostic factors of biochemical recurrence (BCR) in each risk group of prostate cancer patients who underwent low‐dose‐rate brachytherapy (LDR‐BT). Methods: A total of 944 patients with clinically confirmed prostate cancer (cT1c‐3aN0M0) who had underwent LDR‐BT were enrolled. The low‐, intermediate‐, and high‐risk groups included 278, 498, and 168 patients, respectively. The median age, PSA value at diagnosis, and the follow‐up period were 70 years (range: 48–84), 7.2 ng/ml (range: 1.2–113), and 91 months (range: 2–192), respectively. We evaluated the BCR‐free rate, BCR‐free survival, clinical recurrence‐free rate, overall survival (OS), and cancer‐specific survival (CSS). We conducted multivariate analysis to elucidate prognostic factors of BCR for all patients and for each risk group. Results: The 5‐ and 10‐year OS rates were 96.0% and 89.5% and the 5‐ and 10‐year CSS rates were 99.8% and 99.1%, respectively, while the 5‐ and 10‐year BCR‐free rates were 96.6% and 92.5% in low‐risk patients, 95.7% and 90.7% in intermediate‐risk patients and 93.8% and 89.0% in high‐risk patients, respectively. There were no significant differences between the risk groups. Age‐adjusted multivariate analysis indicated biologically effective dose (BED) <180 Gy2 as an independent prognostic factor of BCR in all patients (p = 0.005). There were no independent factors in the low‐ and high‐risk groups, but neoadjuvant androgen deprivation therapy (ADT) (p = 0.022) and BED <180Gy2 (p = 0.042) were independent prognostic factors in the intermediate‐risk group. Conclusions: LDR‐BT can achieve a higher recurrence‐free survival with an adequate local radiation dose (BED ≥ 180 Gy2). [ABSTRACT FROM AUTHOR]

Objectives: To examine the long-term oncological outcomes and urological morbidity of low-dose-rate prostate brachytherapy (LDRBT) monotherapy using live intraoperative dosimetry planning and an automated needle navigation delivery system for the treatment of men with low and intermediate-risk prostate cancer. Patients and Methods: A prospective database of 400 consecutive patients who underwent LDRBT between July 2003 and June 2015 was retrospectively reviewed to assess urinary side-effects and biochemical progression, based on the Phoenix definition and also a definition of a prostate-specific antigen (PSA) level of ≥0.2 µg/L. Results: Minimum patient follow-up was 5.5 years. The median follow-up of the entire cohort was 11.8 years. The median (range) PSA level was 6.1 (0.9-17) µg/L and the median Gleason score was 3 + 4. The biochemical relapse-free survival (RFS; freedom from biochemical recurrence) based on the Phoenix definition was 85.8% (343/400). The RFS using a 'surgical' definition of a PSA level of <0.2 µg/L was 71% (284/400). Of the 297 men followed for ≥10 years, prostate cancer-specific survival (PCSS) was 98% (291/297). Post-LDRBT urethral stricture developed in 11 men (2.8%, 11/400). For men with ≥10 years of follow-up, 22 men (7.4%, 22/297) required a pad for either stress or urge urinary incontinence (UI). UI was identified in only 2.2% (one of 46) of men who had a bladder neck incision (BNI) before LDRBT. Conclusion: LDRBT is associated with excellent PCSS, with a median follow-up of 11.8 years. The risk of post-implantation urethral stricture and UI is low and a pre-implantation BNI for management of bladder outflow obstruction does not increase the risk of UI or urethral stricture. [ABSTRACT FROM AUTHOR]

Low-dose-rate prostate brachytherapy with permanent iodine-125 is an important curative treatment for low-risk prostate cancer, and it has been demonstrated that brachytherapy with permanent seeds is an effective treatment. However, differences in prostate volume, spatial location, and gland deformation between images obtained in the pre-planning phase and those obtained during the implantation procedure affect accurate delivery of the pre-planned dose. Furthermore, the complicated procedure could be a burden to elderly patients, for example, the risks associated with general anesthesia. In addition, ultrasound images are not as clear as computed tomography (CT) images with regard to identifying the location of seeds. Therefore, a newmethod for guidance during the procedure is urgently needed. Here, we have described a new method for precise trans-perirectal insertion of radioactive iodine-125 seeds in patients with prostate cancer under the guidance of CT and a 3D-printed template. These are some of the advantages of this technique over the standard procedure for seed implantation in the prostate: It requires only local anesthesia, the pre-planning phase can be completed before the procedure, and the operation time is considerably shorter. This report describes trans-pararectal iodine-125 seed brachytherapy for prostate cancer under local anesthesia and the guidance of a 3D printed template in two elderly patients. The dose parameters determined in the preoperative planning phase were verified postoperatively and found to be consistent. Further, the procedure was completely successfully with no major complications in both cases, and the patients' prostate-specific antigen levels were normal at the most recent follow-up conducted 50 months after the procedure. Therefore, this technique seems promising for prostate cancer brachytherapy, and its application needs to be researched and extended further in the future. [ABSTRACT FROM AUTHOR]

• Ocular dose limits are necessary to evaluate a novel intraocular shielding method. • Retrospective study reviewed dosimetry and toxicity data for eye plaque patients. • Doses>52 Gy to the macula and 42 Gy to the optic disc should be avoided. • Further work is needed to reduce high doses and improve patients' quality of life. The aim of this study was to relate common toxicity endpoints with dose to the macula, optic disc, and lens for uveal melanoma patients treated with Iodine-125 Collaborative Ocular Melanoma Study (COMS) eye plaque brachytherapy. A cohort of 52 patients treated at a single institution between 2005 and 2019 were retrospectively reviewed. Demographics, dosimetry, and clinical outcomes were recorded. Univariate, relative risk, and Kaplan-Meier analyses were performed to relate dose to toxicity endpoints including retinopathy, vision decline, and cataracts. By the end of follow up (Median = 3.6 years, Range = 0.4 – 13.5 years), 65 % of eyes sustained radiation retinopathy, 40 % demonstrated moderate vision decline (>5 Snellen lines lost), and 56 % developed cataracts. Significant (p < 0.05) risk estimates exist for retinopathy and VA decline for doses >52 Gy to the macula and >42 Gy to the optic disc. Moreover, dose to the lens > 16 Gy showed a significant risk for cataract formation. Kaplan-Meier analysis demonstrated significantly different incidence of radiation retinopathy for > 52 Gy to the macula and > 42 Gy to the optic disc. In addition, the Kaplan-Meier analysis showed significantly different incidence of cataract formation for patients with lens dose > 16 Gy. Dose-effect relationships exist for the macula and optic disc with respect to the loss of visual acuity and the development of retinopathy. To better preserve vision after treatment, further research is needed to reduce macula, optic disc, and lens doses while maintaining tumor control. [ABSTRACT FROM AUTHOR]

Background: To compare chronological changes in lower urinary tract symptoms (LUTS) after low-dose-rate prostate extended-release therapy (LDR-BT) using the overactive bladder symptom score (OABSS) in patients aged ≥ 75 years (elderly group) versus those aged < 75 years (control group). Materials and Methods: Patients with prostate cancer who underwent LDR-BT at Gifu University Hospital were included in this study. The International Prostate Symptom Score (IPSS), OABSS, and quality of life-based on urinary symptoms (IPSS-QOL) were evaluated before and after LDR-BT. We compared chronological changes in IPSS, OABSS, and IPSS-QOL in the elderly group with those in the control group and assessed the association between the resolution of OABSS and clinicopathological covariates. Results: A total of 484 patients were enrolled in this study. In the elderly group, the total IPSS, OABSS, and frequency scores increased at 1 month postoperatively, whereas the control group showed an increase at 3 months postoperatively. Multivariate analysis identified changes from baseline to the maximum OABSS and pre-treatment OABSS as significant predictors of delayed resolution of OABSS after LDR-BT. Conclusions: Changes in pre-treatment OABSS and pre- and post-LDR-BT OABSS values were independent predictors of delayed resolution of OABSS; however, no correlation was found with age.

Although surgery is the treatment of choice for early-stage non-small-cell lung carcinoma, almost two-thirds of patients do not have acceptable pulmonary function for extensive surgeries. The alternative approach for this large group of patients is sublobar resection along with low-dose-rate (LDR) brachytherapy (BT). However, patients with resected lungs have a high risk of recurrence and are often treated with platinum-based (Pt-based) chemotherapy (CT). In this study, we aimed to evaluate the absorbed doses of lung and other thoracic organs, considering concurrent chemo-BT with LDR sources in two modalities: conventional vs. unconventional Pt-based CT. We used the MCNPX code for simulations and to obtain the lung absorbed dose, dose enhancement factor (DEF), and Pt threshold concentration for the abovementioned modalities. Our results indicate that DEF correlates directly with Pt concentration at prescription point and is inversely correlated with depth. Dose enhancement for conventional CT concurrent with BT is <2%, while it is >2% in case of unconventional Pt-based CT wherein the Pt concentration exceeds 0.2 mg/g lung tissue. Also, the absorbed dose of healthy thoracic organs decreased by 2-11% in the latter approach. In conclusion, the concurrent chemo-BT in the lung environment could enhance the therapeutic doses merely by using unconventional CT methods, while lung Pt accumulation exceeds 0.2 mg/g. [ABSTRACT FROM AUTHOR]

This study describes the pattern of failure in patients with biochemical (BCR) recurrence after low-dose-rate (LDR) brachytherapy as a component of definitive treatment for prostate cancer. Patients with BCR after LDR brachytherapy ± external beam radiation therapy (EBRT) were enrolled on prospective IRB approved advanced imaging protocols. Patients underwent 3T multiparametric MRI (mpMRI); a subset underwent prostate specific membrane antigen (PSMA)-based PET/CT. Pathologic confirmation was obtained unless contraindicated. Between January 2011 and April 2021, 51 patients with BCR after brachytherapy (n = 36) or brachytherapy + EBRT (n = 15) underwent mpMRI and were included in this analysis. Of 38 patients with available dosimetry, only two had D90<90%. The prostate and seminal vesicles were a site of failure in 66.7% (n = 34) and 39.2% (n = 20), respectively. PET/CT (n = 32 patients) more often identified lesions pelvic lymph nodes (50%; n = 16) and distant metastases (18.8%; n = 6), than mpMRI. Isolated nodal disease (9.8%; n = 5) and distant metastases (n = 1) without local recurrence were uncommon. Recurrence within the prostate was located in the transition zone in 48.5%, central or midline in 45.5%, and anterior in 36.4% of patients. In this cohort of patients with BCR after LDR brachytherapy ± EBRT, the predominant recurrence pattern was local (prostate ± seminal vesicles) with frequent occurrence in the anterior prostate and transition zone. mpMRI and PSMA PET/CT provided complementary information to localize sites of recurrence, with PSMA PET/CT often confirming mpMRI findings and identifying occult nodal or distant metastases. [ABSTRACT FROM AUTHOR]

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 11C‐Choline or 68Ga‐prostate‐specific membrane antigen (68Ga‐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. [ABSTRACT FROM AUTHOR]

The treatment of borderline resectable (BR) pancreatic cancer is challenging and requires a multidisciplinary approach with chemotherapy, radiation and surgical resection. Despite using chemotherapy and radiotherapy in the neoadjuvant setting, achievement of negative surgical margins remains technically challenging. Positive margins are associated with increased local recurrences and worse overall survival and there are no standard options for treatment. The CivaSheet is an FDA-cleared implantable sheet with a matrix of unidirectional planar low-dose-rate (LDR) Palladium-103 (Pd-103) sources. The sources are shielded on one side with gold to spare radio-sensitive structures such as the bowel. The sheet can easily be customized and implanted at the time of surgery when there is concern for close or positive margins. The CivaSheet provides an interesting solution to target the region of close/positive margins after pancreatectomy. Here we discuss the physical properties, the dosimetry, clinical workflow and early patient outcomes with the CivaSheet in pancreatic cancer. [ABSTRACT FROM AUTHOR]

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 < 0.001) and low‐dose‐rate brachytherapy with external beam radiation therapy group (P = 0.003). Prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly and negatively correlated with the postimplant D90. The prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly higher in patients with neoadjuvant androgen deprivation therapy than those without neoadjuvant androgen deprivation therapy (P < 0.001). Conclusions: Neoadjuvant androgen deprivation therapy decreased postimplant D90 with substantial prostate gland swelling after low‐dose‐rate brachytherapy. When neoadjuvant androgen deprivation therapy is required to reduce prostate volume for patients with large prostate glands and offer adequate local control for patients with high‐risk prostate cancer before low‐dose‐rate brachytherapy, intraoperative D90 adjustment might be necessary. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effects of naftopidil and silodosin administration on the quality of life of patients with prostate cancer who underwent low‐dose‐rate brachytherapy. Methods: In total, 141 men diagnosed with localized prostate cancer who were treated with low‐dose‐rate brachytherapy were enrolled. Patients were randomized (1:1) to the naftopidil (75 mg/day, n = 63) or silodosin group (8 mg/day, n = 64). Naftopidil and silodosin were administered 1 day after low‐dose‐rate brachytherapy, and were continued for at least 3 months. Using the University of California at Los Angeles Prostate Cancer Index and Sexual Health Inventory for Men scores, the mean changes and rates of deterioration from baseline were compared. The deterioration rates in the quality of life of patients at 1 and 3 months after low‐dose‐rate brachytherapy were evaluated based on the minimal important difference. Results: The rates of deterioration from baseline to 1 and 3 months after low‐dose‐rate brachytherapy were not significantly different between the two groups in terms of urinary function, urinary bother, bowel bother, sexual function or Sexual Health Inventory for Men scores. In contrast, there were significant differences in bowel function (naftopidil 1 month, 52%; 3 months, 52%; silodosin 1 month, 28%; 3 months, 34%; 1 month, P < 0.01; 3 months, P = 0.048) and sexual bother (naftopidil 3 months, 11%; silodosin 3 months, 29%; P = 0.01). Conclusions: Naftopidil and silodosin provide different disease‐specific quality of life outcomes in patients undergoing, especially in terms of bowel function and sexual bother. These findings can help in the selection of α‐1 adrenoceptor antagonists after low‐dose‐rate brachytherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Small cell carcinoma of the prostate is a rare condition with important differences from prostatic adenocarcinoma in terms of clinical and prognostic characteristics. A low prostate-specific antigen and a symptomatic patient, including paraneoplastic symptoms, characterize small cell carcinoma of the prostate. Diagnosis is made on the basis of prostate biopsy, and fluorodeoxyglucose positron emission tomography/computed tomography is often used for staging because up to 60% of patients present with de novo metastatic disease. Patients with metastatic disease are usually treated with platinum-based cytotoxic chemotherapy regimens similar to those used for small cell carcinoma of the lung. However, prognosis remains poor, with a median overall survival of 9 to 17 months despite therapy. Case presentation This report describes a case of an 80-year-old Caucasian patient with lymph node and bone metastatic small cell carcinoma of the prostate following low-dose-rate brachytherapy for a low-risk prostate carcinoma and treated with chemotherapy and immunotherapy. Conclusion Low-dose-rate brachytherapy might be an etiology of small cell prostate cancer.

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). 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. 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 < 0.05). Prostate cancer-specific mortality was low in both EBRT (1%) and LDR-BT (2%) cohorts. No significant difference in OS was found between LDR-BT and EBRT in low- and intermediate-risk group (HR 2.1, p = 0.2 and HR = 1.7, p = 0.3). In our retrospective study, LDR-BT is associated with superior bFFS compared with EBRT in Asian men with intermediate-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Low-dose-rate brachytherapy is a key treatment for low-risk or favorable intermediate-risk prostate cancer. The number of radioactive seeds inserted during the procedure depends on prostate volume, and is not easy to predict without pre-planning. Consequently, a large number of unused seeds may be left after treatment. The objective of the present study was to predict the exact number of seeds for future patients using machine learning and a database of 409 treatments. Material and methods: Database consisted of 18 dosimetric and efficiency parameters for each of 409 cases. Nine predictive algorithms based on machine-learning were compared in this database, which was divided into training group (80%) and test group (20%). Ten-fold cross-validation was applied to obtain robust statistics. The best algorithm was then used to build an abacus able to predict number of implanted seeds from expected prostate volume only. As an evaluation, the abacus was also applied on an independent series of 38 consecutive patients. Results: The best coefficients of determination R2 were given by support vector regression, with values attaining 0.928, 0.948, and 0.968 for training set, test set, and whole set, respectively. In terms of predicted seeds in test group, mean square error, median absolute error, mean absolute error, and maximum error were 2.55, 0.92, 1.21, and 7.29, respectively. The use of obtained abacus in 38 additional patients resulted in saving of 493 seeds (393 vs. 886 remaining seeds). Conclusions: Machine-learning-based abacus proposed in this study aims at estimating the necessary number of seeds for future patients according to past experience. This new abacus, based on 409 treatments and successfully tested in 38 new patients, is a good alternative to non-specific recommendations. [ABSTRACT FROM AUTHOR]

To examine medium-term outcomes of hemi-gland low-dose-rate brachytherapy as a primary treatment for intermediate-risk prostate cancer. We recruited intermediate-risk unilateral prostate cancer patients for a prospective trial of hemi-gland brachytherapy. Twenty-four patients underwent hemi-gland iodine-125 seed implantation with a prescribed dose of 160 Gy. Serum prostate-specific antigen (PSA) was measured regularly and follow-up biopsy was scheduled after 2–3 years of treatment. When clinically needed afterward, for-cause biopsy was performed to confirm pathology. Treatment failure (TF)-free survival, which was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality, was assessed, as was biochemical failure (BF)-free survival. Urinary and sexual functions were also evaluated. Median follow-up duration was 61 months. Twenty-two patients (92%) exhibited a declining trend or decreased value of PSA for 12 months or longer after the treatment. Follow-up biopsy in the initial triennium and for-cause biopsy in the subsequent triennium were performed in 16 and four patients, respectively, and cancer was found from the treated lobe in one patient (4% of the cohort) and significant cancer was found from untreated lobes in four patients (17%) in total. Secondary treatments were performed in six patients successfully. Five-year freedom from BF, TF, and metastasis was 71%, 90%, and 100%, respectively. The International Prostate Symptom Score significantly deteriorated at 3 months and reversed itself afterward. The International Index of Erectile Function 5 had no significant decrease. Hemi-gland low-dose-rate brachytherapy provides favorable medium-term oncological outcomes with genito-urinary functional preservation for men with intermediate-risk unilateral prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: In low-dose-rate prostate brachytherapy (LDR-PB), treatment planning is the process of determining the arrangement of implantable radioactive sources that radiates the prostate while sparing healthy surrounding tissues. Currently, these plans are prepared manually by experts incorporating the centre's planning style and guidelines. In this article, we develop a novel framework that can learn a centre's planning strategy and automatically reproduce rapid clinically acceptable plans. Methods: The proposed framework is based on conditional generative adversarial networks that learn our centre's planning style using a pool of 931 historical LDR-PB planning data. Two additional losses that help constrain prohibited needle patterns and produce similar-looking plans are also proposed. Once trained, this model generates an initial distribution of needles which is passed to a planner. The planner then initializes the sources based on the predicted needles and uses a simulated annealing algorithm to optimize their locations further. Results: Quantitative analysis was carried out on 170 cases which showed the generated plans having similar dosimetry to that of the manual plans but with significantly lower planning durations. Indeed, on the test cases, the clinical target volumes achieving 100 % of the prescribed dose for the generated plans was on average 98.98 % ( 99.36 % for manual plans) with an average planning time of 3.04 ± 1.1 min ( 20 ± 10 min for manual plans). Further qualitative analysis was conducted by an expert planner who accepted 90 % of the plans with some changes ( 60 % requiring minor changes & 30 % requiring major changes). Conclusion: The proposed framework demonstrated the ability to rapidly generate quality treatment plans that not only fulfil the dosimetric requirements but also takes into account the centre's planning style. Adoption of such a framework would save significant amount of time and resources spent on every patient; boosting the overall operational efficiency of this treatment. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the incidence of rectal toxicity and to identify the associated dosimetric predictive parameters after I-125 seed low-dose-rate brachytherapy (LDR-BT) combined with volumetric modulated arc therapy (VMAT) and dose constraints. In total, 110 patients with high-risk prostate cancer received 110 Gy LDR-BT, followed by 45 Gy VMAT. Rectal toxicity was recorded according to Common Terminology Criteria for Adverse Events v.4.03. The dosimetric factors associated with LDR-BT and VMAT were analyzed to determine their relationship with rectal toxicity. Receiver operating characteristic (ROC) curve analysis was performed for ≥ grade 2 (G2) rectal toxicity prediction. The follow-up duration was 10.1–115.2 months (median 60.5 months). Seven patients had G2 rectal hemorrhage, and none of the patients had grade 3 rectal hemorrhage. In the univariate analysis, the rectal volume receiving 100% of the prescribed dose (rV 100) (p < 0.001), the dose covering 2 cc of the rectum (rD 2cc) during LDR-BT (p = 0.002), and the combined rD 2cc during LDR-BT and VMAT (p = 0.001) were identified as predictors of G2 rectal hemorrhage. In the ROC curve analysis, the cutoff value was 0.46 cc for rV 100 , 74.0 Gy for rD 2cc , and 86.8 GyEQD 2 for combined rD 2cc. Predictors of late ≥ G2 rectal hemorrhage are rV 100 , rD 2cc , and combined rD 2cc. The incidence of rectal toxicity is low and acceptable in this setting and is highly dependent on the rectal dose of LDR-BT. The use of higher-quality LDR-BT and VMAT dose constraints may further reduce the rate of rectal hemorrhage. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Salvage brachytherapy produces long-term biochemical control in select patients. • Grade group and PSA at diagnosis may predict post-salvage failure. • Toxicity was acceptable, with low rates of severe adverse events. • Salvage brachytherapy is a promising approach for locally recurrent prostate cancer. We sought to describe the safety and efficacy of salvage low dose rate (LDR) brachytherapy for local prostate cancer recurrence following definitive RT. We included patients from two prospectively maintained institutional databases who underwent salvage LDR brachytherapy for biopsy confirmed intra-prostatic recurrence following primary RT. All patients were without evidence of metastatic disease. Freedom from biochemical failure (FFbF), prostate cancer specific survival (PCaSS), and overall survival (OS) were determined using the Kaplan–Meier estimates. Cox proportional hazard models were used to identify factors predictive of FFbF. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 108 patients were included. Median follow-up was 6.3 years. The 5- and 10-year actuarial survival outcomes were as follows: FFbF, 63.1% and 52.0%; PCaSS, 90.5% and 77.8%; OS, 80.9% and 56.7%. On multivariate modeling, increasing grade group (HR 1.41, 95% CI 1.02–1.95, p = 0.036) and initial PSA at diagnosis (HR 1.02, 95% CI 1.004–1.05, p = 0.022) were associated with worse FFbF. Grade 3 toxicity occurred in 16.7% of patients; including genitourinary events in 15.7% and gastrointestinal events in 2.8% of patients. IPSS scores increased following implant, peaking at 2 months (median IPSS 20, p = 0.002) and thereafter remaining elevated throughout follow-up. Salvage LDR brachytherapy is safe and efficacious, with acceptable grade 3+ toxicity and good biochemical control on long-term follow-up. Patients with higher grade group and higher PSA at initial diagnosis may be at increased risk for biochemical failure. [ABSTRACT FROM AUTHOR]

The aim of this work was to analyze the exposure rates measured in the proximity of patients who underwent prostate low-dose-rate brachytherapy with I-125 implant. Effective doses to relatives and to population were computed to estimate the time to reach radioprotection dose constraints. Measurements were obtained from 180 patients, whereas the body mass index was calculated and reported for 77 patients. The day after the implant, K ˙ measurements were conducted at various skin distances and positions and converted to effective doses. A theoretical model was developed to estimate effective doses from total implanted activity. The latter was approximated with a 10-mL vial inside the patient. The K ˙ measurements showed a low correlation with the total implanted activity, albeit an increasing trend of K ˙ was observed on increasing the activity. A stronger correlation was found between body mass index and K ˙ measurements. The effective dose to population is in general lower than dose constraints as well as the effective doses to relatives, with the exception of children and pregnant women, who command special precautions. We report differences between the experimental model– and theoretical model–based dose evaluation together with their comparison with previous studies found in literature. Based on the K ˙ measurements and the results of the present analysis, it is possible to provide the patient with radiation safety instructions specifically tailored to his relatives' habits and working environment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate international prostate symptom score and urinary quality of life in patients with prostate cancer who underwent low-dose-rate brachytherapy, and to identify lower urinary tract symptoms that must be improved to enhance post-operative urinary quality of life and factors associated with lower urinary tract symptoms., Material and Methods: This study included 193 patients who underwent low-dose-rate brachytherapy alone (145 Gy). Importance-performance analysis was conducted to identify lower urinary tract symptoms that should be prioritized to improve urinary quality of life. Association between lower urinary tract symptom scores and each factor was investigated. Receiver operating characteristic curve analysis was used to evaluate dosimetric parameters related to lower urinary tract symptom score to predict an average score of ≥ 3. Cut-off values were determined., Results: One to nine months post-implantation was a period of significantly increased urinary quality of life scores compared with baseline ( p < 0.05 each). The importance-performance analysis conducted for 1-9 months revealed that frequency, nocturia, and weak stream required improvement. Multivariate analysis showed that each lower urinary tract symptom score presented a significant association with its baseline value ( p < 0.001 each, positive correlation). Frequency, incomplete emptying, urgency, and straining scores were significantly associated with prostate volume, whereas weak stream and intermittency scores were associated with dose covering 90% of the prostate and dose covering 90% of the urethra, respectively ( p < 0.05 each, positive correlations). Cut-off values for these doses were 167.01 Gy and 136.84 Gy, respectively., Conclusions: This study highlights the importance of prioritizing specific lower urinary tract symptoms for improvement in post-operative urinary quality of life, and identifies the associated factors that can help in personalized treatment planning and goal-setting for better patient satisfaction., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Termedia.)

Background: Radiotherapy is one of the most frequently selected treatment options for patients with prostate cancer. However, adverse effects related to the irradiated surrounding normal organs are significant clinical concerns. Specifically, genitourinary and gastrointestinal toxicities can lead to a dramatically reduced quality of life. The aim of this clinical trial is to determine the efficacy of oral 5-aminolevulinic acid (ALA) phosphate with sodium ferrous citrate (SFC) in patients treated with low-dose-rate brachytherapy (LDR-BT) using an iodine-125 seed source. Methods: The AMBER study is a prospective, single-center trial in patients with localized prostate cancer undergoing LDR-BT. Patients who undergo supplementary extra-beam radiotherapy are excluded, whereas those who undergo pre-implantation short-term (4–6 months) androgen deprivation therapy to decrease the prostate volume and/or improve oncological outcomes are included. After the screening and registration, the patients will be instructed to take capsules of ALA-SFC twice a day (200 mg and 229.42 mg per day) for 6 months from the day of seed implantation (prescribed radiation dose of 160 Gy). Patient data will be collected before the implantation; during oral ALA-SFC treatment; and 1, 3, 6, 9, and 12 month(s) after seed implantation. The primary endpoint of this trial is the urinary frequency 3 months after seed implantation. At each visit, the 24-h urinary frequency, total voided volume, and mean voided volume on a frequency volume chart and other patient-reported outcomes are recorded. The data of the trial cases will be compared with those of historical controls, who are consecutive patients undergoing LDR-BT without supplementary extra-beam radiotherapy between January 2016 and January 2019. The number of subjects has been set to be 50 for trial cases and 150 for the historical control cases. Pre- and post-treatment clinicopathologic factors are compared between two groups. Discussion: The goal of this trial is to determine the potential benefit of ALA-SFC in patients who undergo LDR-BT. To the best of our knowledge, this is the first study investigating the potential clinical benefit of oral ALA-SFC after radiotherapy. More evidence from a further randomized controlled trial is needed to change the standard of care and lead to better post-radiotherapy management. Trial registration: This clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 5 December 2019. The reference number is jRCTs051190077, nara0013 (Certified Review Board of Nara Medical University).

Background: Small cell carcinoma of the prostate is a rare condition with important differences from prostatic adenocarcinoma in terms of clinical and prognostic characteristics. A low prostate-specific antigen and a symptomatic patient, including paraneoplastic symptoms, characterize small cell carcinoma of the prostate. Diagnosis is made on the basis of prostate biopsy, and fluorodeoxyglucose positron emission tomography/computed tomography is often used for staging because up to 60% of patients present with de novo metastatic disease. Patients with metastatic disease are usually treated with platinum-based cytotoxic chemotherapy regimens similar to those used for small cell carcinoma of the lung. However, prognosis remains poor, with a median overall survival of 9 to 17 months despite therapy.Case Presentation: This report describes a case of an 80-year-old Caucasian patient with lymph node and bone metastatic small cell carcinoma of the prostate following low-dose-rate brachytherapy for a low-risk prostate carcinoma and treated with chemotherapy and immunotherapy.Conclusion: Low-dose-rate brachytherapy might be an etiology of small cell prostate cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare an isotropic three-dimensional (3D) T2-weighted sequence sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) with an axial two-dimensional T2-weighted turbo spin echo (TSE) sequence with regard to overall image quality and the delineation of normal prostate and periprostatic anatomy for low-dose-rate prostate cancer brachytherapy planning evaluation. Patients (n = 69) with prostate cancer who had pelvic magnetic resonance imaging (MRI) for low-dose-rate brachytherapy treatment planning were included. Three radiologists independently assessed the visibility of nine anatomic structures on each sequence by using a 5-point scale and overall image quality by using a 4-point scale. The significance of the differences in diagnostic performance was tested with a Wilcoxon signed rank test. No significant intersequence differences were found for most (7/9) anatomical structures and overall image quality. The mean scores for visibility of anatomical structures on the 3D SPACE and 2D TSE sequences, respectively, were as follows: the zonal anatomy (3.7; 3.9, p = 0.05), prostate capsule (3.9; 4.0, p = 0.08), neurovascular bundle (2.9; 2.9, p = 0.9), rectoprostatic angle (3.8; 3.8, p = 0.35), rectum (4.2; 4.3, p = 0.26), urethra (3.8; 3.9, p = 0.12), urinary bladder (4.6; 4.6, p = 0.61), and overall image quality (2.9; 2.9, p = 0.33). 3D SPACE was superior for delineation of the genitourinary diaphragm (3.8; 3.6, p = 0.003), whereas 2D TSE was superior for delineation of the seminal vesicles (3.5; 4.0, p < 0.0001). Anatomic delineation of the prostatic and periprostatic anatomy provided by the 3D SPACE sequence is as robust in quality as that provided by a conventional 2D TSE sequence with superior delineation of the genitourinary diaphragm. For MRI-based brachytherapy treatment planning, the 3D SPACE sequence with subcentimeter isotropic resolution can replace the 2D TSE sequence and be incorporated into standard MRI protocols. [ABSTRACT FROM AUTHOR]

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 125I 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 <10 ng/mL (P < 0.001). D'Amico Risk groups were significantly associated with BRFS (P < 0.001), with a hazard ratio of 2.38 for intermediate‐ and high‐risk patients vs low‐risk patients. The radiation dose covering 90% of the prostate volume (D90) after 6 weeks was significantly lower in patients with recurrence. Functional outcomes returned close to baseline levels after 2–3 years. A major limitation of these findings is a substantial loss to follow‐up. Conclusion: Our results are in line with other studies showing that LDR‐BT is associated with good oncological outcomes together with good functional results. [ABSTRACT FROM AUTHOR]

To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]