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Le cancer de la prostate est le plus fréquent chez l'homme et, au stade localisé, les schémas d'hypofractionnement de la radiothérapie sont devenus des standards, mais l'absence de risque aggravé de toxicité aiguë et tardive génito-urinaire et gastro-intestinale de l'escalade de dose reste à prouver. La population étudiée comprenait tous les patients pris en charge à l'institut Curie de février 2016 à mars 2018 pour un adénocarcinome prostatique localisé traité par irradiation externe délivrée par un accélérateur linéaire en technique conformationnelle avec modulation d'intensité guidée par l'image à la dose totale de 75 Gy en 30 fractions de 2,5 Gy dans le volume cible prévisionnel comprenant la prostate et les vésicules séminales proximales, et pouvait associer une radiothérapie prophylactique ganglionnaire de 46 Gy en 23 fractions avec la technique de boost intégré. En tout, 166 patients ont été inclus, dont 114 étaient atteints de cancer de risque au moins intermédiaire défavorable (soit 68,7 %). L'âge et le suivi médians étaient de 71,4 ans et 3,96 ans. Cent quarante-neuf patients ont reçu une radiothérapie ganglionnaire (soit 89,8 %). Cent trente et un patients ont reçu une hormonothérapie (soit 78,9 %). Une toxicité génito-urinaire de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans respectivement dans 36,7 %, 8,8 %, 3,1 % et 4,7 % des cas. Deux patients ont souffert à 5 ans d'une toxicité de grade 4 (soit 1,6 %). Une toxicité gastro-intestinale de grade 2 ou plus a été notée en cours de radiothérapie, à 6 mois, 1 an et 5 ans dans respectivement 15,1 %, 1,9 %, 14,6 % et 9,3 % des cas. Parmi ces derniers, huit patients ont souffert d'une toxicité de grade 3 (soit 6,2 %). Il n'y a eu aucune toxicité de grade 4. Les analyses n'ont pas mis en évidence de facteur prédictif de toxicité. Les taux de survie globale, sans progression et spécifique à 5 ans étaient respectivement de 82,4 %, 85,7 % et 93,3 %. La concentration sérique d'antigène spécifique de la prostate et les facteurs de risque cardiovasculaires ont été retrouvés comme facteurs prédictifs d'une dégradation de la survie globale (p = 0,0028 pour les deux). La radiothérapie externe pour un cancer prostatique localisé avec notre schéma modérément hypofractionné avec escalade de dose est bien tolérée. En l'absence de toxicité tardive majorée, l'analyse des modes de rechutes à long terme sera intéressante pour déterminer l'intérêt de cette escalade de dose sur les rechutes locales et à distance. Prostate cancer is the most frequent cancer among men and radiotherapy hypofractionation regimens have become standard treatments for the localized stages, but the absence of increased risk of acute and late genitourinary or gastrointestinal toxicity of the dose escalation still must be demonstrated. The study population included all patients with localized prostatic adenocarcinoma treated at the institut Curie from February 2016 to March 2018 by external radiation delivered by a linear accelerator using an image-guided conformal intensity modulation technique at a total dose of 75 Gy in 30 fractions of 2.5 Gy in the planning target volume that included the prostate and the proximal seminal vesicles, and could be paired with a prophylactic lymph node radiotherapy at 46 Gy in 23 fractions with simultaneous integrated boost. A total of 166 patients were included. Among them, 68.6% were unfavourable intermediate or (very) high risk. The median age and follow-up were 71.4 years and 3.96 years. One hundred and forty-nine patients received prophylactic lymph node radiotherapy (89.8%). One hundred and thirty-one patients received hormonotherapy (78.9%). Genito-urinary toxicity events of grades 2 or above during radiotherapy, at 6 months, 1 year and 5 years were respectively 36.7%, 8.8%, 3.1% and 4.7%. Two patients had late grade 4 toxicity at 5 years (1.6%). Grade 2 gastrointestinal toxicity events during radiotherapy, 6 months, 1 year and 5 years were respectively 15.1%, 1.9%, 14.6% and 9.3%. Of these, eight patients had grade 3 toxicity (6.2%). There was no grade 4 toxicity. Analyses did not reveal any predictive factor for toxicity. The 5-year overall, progression-free, and specific survival rates were respectively 82.4%, 85.7%, and 93.3%. Serum prostate specific antigen concentration and cardiovascular risk factors were found to be predictive factors of deterioration in overall survival (P = 0.0028 for both). External radiotherapy for localized prostatic cancer with our moderately hypofractionated dose escalation regimen is well tolerated. In the absence of increased late toxicity, the analysis of the modes of long-term relapses will be interesting to determine the benefit of this dose escalation on local and distant relapses. [ABSTRACT FROM AUTHOR]

The evolution of radiation therapy techniques goes hand in hand with the evolution of the profession of radiation therapist. In the particular context of online adaptive radiotherapy based on cone beam computed tomography images, delegation of certain tasks from the physician to the radiation therapist is possible within the framework of a cooperation protocol. This delegation requires prior theoretical and practical training. It enriches the practice of radiation therapists by allowing them to acquire new skills and greater autonomy. It foreshadows access for radiation therapists to advanced practice. [ABSTRACT FROM AUTHOR]

Erectile function preservation is an important quality of life factor in patients treated for prostate cancer. A dose-optimization approach on sexual structures was developed and evaluated to limit erectile dysfunction after radiotherapy. Twenty-three men with localized prostate cancer and no erectile dysfunction were enrolled in the study. All patients received a prescription dose between 76 and 78 Gy. Computed tomography/magnetic resonance image registration was used to delineate the prostatic volume and the sexual structures: internal pudendal arteries (IPA), penile bulb and corpus cavernosum. Erectile function was evaluated using the 5-items International Index of Erectile Function (IIEF-5) score every 6 months during the 2 years after radiotherapy and once a year afterwards. No erectile dysfunction, mild erectile dysfunction and severe erectile dysfunction were defined if the IIEF-5 scores were 20–25, 17–19 and < 17, respectively. The mean follow-up was 4.5 years. The mean age of the patients was 66.3 years. At 2 years, 67% of the patients had no erectile dysfunction, 11% had mild erectile dysfunction and 22% had severe erectile dysfunction. No significant difference was found between the patients with and without erectile dysfunction (IIEF-5 ≥ 20 and IIEF-5 < 20, respectively) for any of the parameters: dosimetric values (internal pudendal arteries, penile bulb, corpus cavernosum), age, comorbidity and smoking status. The biochemical-relapse free survival was 100% at 2 years. This approach with dose-optimization on sexual structures for localized prostate cancer found excellent results on erectile function preservation after radiotherapy, with 78% of the patients with no or mild erectile dysfunction at 2 years. [ABSTRACT FROM AUTHOR]

We investigated the association between pre-existing comorbidities and prostate cancer management. High overall comorbidity burden, cardiac and respiratory disorders, thrombosis, diabetes, depression and anxiety, and chronic pain were associated with selecting EBRT, ADT alone or watchful waiting over RP. Introduction: We aimed to assess the association between comorbidities and prostate cancer management. Patients and methods: We studied 12,603 South Australian men diagnosed with prostate cancer between 2003 and 2019. Comorbidity was measured one year prior to prostate cancer diagnosis using a medication-based comorbidity index (Rx-Risk). Binomial logistic regression analyses were used to assess the association between comorbidities and primary treatment selection (active surveillance, radical prostatectomy (RP), external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT), brachytherapy, ADT alone, and watchful waiting (WW)). Certain common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and chronic pain) were also assessed. All models were adjusted for sociodemographic and tumor characteristics. Results: Likelihood of receiving RP was lower among men with Rx-Risk score ≥3 (odds ratio (OR) 0.62, 95%CI:0.56-0.69) and Rx-Risk 2 (OR 0.80, 95%CI:0.70-0.92) compared with no comorbidity (Rx-Risk ≤0). Men with high comorbidity (Rx-Risk ≥3) were more likely to have received ADT alone (OR 1.76, 95%CI:1.40-2.21), EBRT (OR 1.30, 95%CI:1.17-1.45) or WW (OR 1.49, 95%CI:1.19-1.88) compared with Rx-Risk ≤0. Pre-existing cardiac and respiratory disorders, thrombosis, diabetes, depression and anxiety, and chronic pain were associated with lower likelihood of selecting RP and higher likelihood of EBRT (except chronic airway disease) or WW (except diabetes and depression and anxiety). Cardiac disorders and thrombosis were associated with higher likelihood of selecting ADT alone. Furthermore, age had greater effect on treatment choice than the level of comorbidit y. Conclusion: High comorbidit y burden was associated with primary treatment choice, with significantly less RP and more EBRT, WW and ADT alone among men with higher levels of comorbidity. Each of the individual comorbid conditions also influenced treatment selection. [ABSTRACT FROM AUTHOR]

A study of 3425 men showed that those with STAR-CAP stages 1A-1C had similar risk of needing additional therapies and developing metastases after primary treatment. Stages 2A to 3B increased the risk of these outcomes. Men who underwent surgery were more likely to receive subsequent therapy, while radiation therapy patients were more likely to receive upfront intensified multimodality therapies. Introduction: The International Staging Collaboration for Prostate Cancer (STAR-CAP) has been proposed as a risk model for prostate cancer with superior prognostic power compared to the current staging system. This study aimed to evaluate the performance of STAR-CAP in predicting the risk of subsequent therapy after initial treatment and the risk of developing metastases. Patients and Methods: The study included 3425 men from an institutional observational registry with a median age of 64.9 years and a median follow-up time of 5.4 years. The primary endpoints were metastases and progression to additional therapy after initial therapy (radiation ± surgery). The risk of progression in the STAR-CAP group was estimated using a competing risk model (death). Results: The results showed that patients with STAR-CAP stages 1A-1C had a similar risk of requiring additional therapies and developing metastasis. Compared to stage IC, each stage from 2A to 3B incrementally increased the risk of subsequent therapy (hazard ratio (HR) 1.4-5.8, respectively) and metastases (HR 1.5-10.8, respectively). The 5-year probability of receiving subsequent therapy for a patient with stage IC was 8.6%, which increased from 11.4% to 37.4% for those with stages 2A to 3B. The 5-year probability of developing metastases for patients with stage IC was 1.5%, which increased from 2.2% to 8.2% for patients with stages 2A to 3B. Conclusions: The probability of receiving subsequent therapy was higher for patients undergoing surgery, while radiation therapy patients were more likely to receive treatment with intensified multimodality therapies upfront. [ABSTRACT FROM AUTHOR]

Purpose: Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort. Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010– 2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50–79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/ watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D’Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes. Results: After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81–0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41–0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death. Conclusions: Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation - especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group. [ABSTRACT FROM AUTHOR]

This prospective study investigated the health-related quality of life (HRQoL) of the patients with an early prostate cancer (PC) treated with radiotherapy (RT) without hormonal treatment compared to that in the agestandardized general male population. Patients have equal overall HRQoL measured with the 15D instrument compared to the general male population. Patients had more depression at the beginning of RT, and their sexual activity remained at a lower level after RT. Background: The effects of radiotherapy (RT) patients' health-related quality of life (HRQoL) are usually compared to those of other treatment modalities instead of HRQoL of the general population in oncological studies. We examined HRQoL of patients with an early prostate cancer (PC) not receiving hormonal treatment up to 3 years after RT using the 15D instrument and the FACT-P questionnaire. Methods: The 15D results were compared to those in the agestandardized general male population (N = 952) using an independent-sample t test. The study population (N = 73) received RT either with 78/2 Gy, 60/3 Gy or 36.25/7.25 Gy fractionation. Results: No significant differences in the mean total HRQoL scores were found between the RT groups and the general male population at any time point. Patients with PC had more depression (P = .015) and distress (P = .029) than the general male population before the treatment and depression up to 3 months after treatment (P = .019), which did not persist at 3 years. The sexual activity dimension had declined by the end of treatment, and this decline persisted 3 years later (P = .033). Excretion functions were worse compared to those in peers at the end of treatment (P < .001) but no longer at 3 months and later after RT. Regarding the FACT-P, HRQoL remained good at 3 years after RT in all the treatment groups and there were no significant differences between the different RT groups at this time point. Conclusion: This study demonstrated that patients treated with RT for early PC had similar HRQoL compared to the age-standardized general male population at 3 years after treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort. Methods: Patients who underwent 68 Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS. Results: Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values ≥ median (p = 0.071), SUVmax values ≥ 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1–4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results. Conclusion: The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology—Genitourinary. [ABSTRACT FROM AUTHOR]

Prostate radiotherapy is associated with worse outcomes in bladder cancer, but the effect on BCG efficacy is not well-characterized. In our single-institution retrospective study we evaluated BCG outcomes in NMIBC patients who have undergone prostate radiotherapy compared to patients with no prior history. The risk of recurrence after BCG for NMIBC does not vary according to prior prostate radiation treatment. Introduction: Prostate radiotherapy is associated with worse oncologic outcomes in patients with bladder cancer. The underlying mechanism is incompletely understood but is thought to be related to an altered microenvironment promoting tumorigenesis. However, there is a gap in the literature regarding how the effect of BCG varies according to prior radiotherapy in patients with non-muscle invasive bladder cancer (NMIBC). In this context, we sought to evaluate oncologic outcomes in NMIBC patients who have previously undergone prostate radiotherapy compared to patients with no prior history of pelvic radiotherapy. Methods: This is a retrospective cohort study that includes all patients who received intravesical for NMIBC at our institution from 2001 to 2019. Patients were stratified into 3 cohorts: prior radiotherapy (RT), radical prostatectomy (RP), and no prostate cancer (No PCa). The outcomes of interest were recurrence at 1-year, progression to muscle-invasive bladder cancer (MIBC), and progression to metastatic disease. Comparisons were also made bet ween cohor ts with respect to elapsed time from radiation therapy. Wilcoxon ranksum test was used for comparing continuous variables, while 2 and Fischer's exact tests were used to examine categor ical var iables. Results: In 199 total patients who underwent BCG for NMIBC, 23 had a prior history of prostate radiotherapy treatment, while 17 underwent prior radical prostatectomy. Overall, 41.2% of patients had recurrence at 1 year. There was no difference in the number of induction or maintenance BCG administrations received between the cohorts within the first year. There was no significant difference in recurrence at 1 year between the 3 cohorts (P = .56). There was also no difference in progression to MIBC or progression to metastatic disease with P = .50 and 0.89, respectively. Conclusion: The risk of recurrence after induction BCG treatment for high-grade NMIBC does not vary according to prior radiation treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

Aim: In this study, patients who underwent salvage Radiotherapy (RT) after biochemical recurrence (BCR) were evaluated retrospectively. The aim of this study was to evaluate the factors affecting the time to biochemical recurrence and salvage RT after radical prostatectomy. Materials and Methods: In Ankara Atatürk Education Hospital, patients with prostate cancer who received salvage RT between 01.01.2011 and 01.01.2018 were analyzed retrospectively. Patients who had undergone radical prostatectomy for prostate adenocarcinoma, and received salvage RT for PSA (Prostate-specific antigen) recurrence, were included. Patients who received post-surgery hormone therapy, and received definitive or palliative RT, were excluded. SPSS Ver. 22 software package was used for statistical analysis and the statistical significance limit was accepted as p≤0.05. Results: Results of 84 patients who met the criteria of the study were analyzed. The median follow-up was 78.5 (range 28-172) months and the median time between surgery and RT was 23.7 (range 5.1-136.9) months. The relationship between the time from surgery to BCR and the Gleason Score (GS) was statistically significant; the median time was 16.3 (2.17-125.9) months in the group with GS ≤8, and 8.9 (2.8-20.3) months in the group with GS 9-10 (p=0.05). The relationship between the time from surgery to BCR and Tumor (T) stage was statistically significant. In subgroup analysis, this difference was seen between T3A and T3B stages. That time was 17.8 (range 2.17-73.77) months in T3A and 8.7 (range 2.8-29.6) months in T3B stages (p=0.02). The relationship between the level of nadir PSA and the median time between surgery and BCR was significant. It was median 20.6 (range 5.4-65.2) months in patients with PSA< 0.03 and 8.8 (range 2.2-125.9) months in patients with PSA ≥0.03 (p<0.0001). Conclusion: BCR time is shorter in patients with high GS, advanced T stage, and high postoperative PSA nadir. [ABSTRACT FROM AUTHOR]

Purpose: Determine the time-dependent magnitude of intrafraction prostate displacement and a cutoff for the tracking decision. Methods: Nine patients with localized prostate cancer were treated with ultra-hypofractionated radiotherapy (CyberKnife) with fiducial markers. Exact tract kV/kV imaging was used with an average interval of 19–92 s. A Gaussian distribution was calculated for the x-, y-, and z-directions (σx,y,z). The variation of prostate motion (μσ) was obtained by averaging the patients' specifics, and the safety margin was calculated to be MAB = WYm + WBSs. Results: The calculated PTV safety margins were as follows: at 40 s: 0.55 mm (L/r), 0.85 mm (a/p), and 1.05 mm (s/i); at 60 s: 0.9 mm (L/r), 1.35 mm (a/p), and 1.55 mm (s/i); at 100 s: 1.5 mm (L/r), 2.3 mm (a/p), and 2.6 mm (s/i); at 150 s: 1.9 mm (L/r), 3.1 mm (a/p), and 3.6 mm (s/i); at 200 s: 2.2 mm (L/r), 3.8 mm (a/p), and 4.2 mm (s/i); and at 300 s: 2.6 mm (L/r), 5.3 mm (a/p), and 5.6 mm (s/i). A tracking cutoff of 2.5 min seemed reasonable. In order to achieve an accuracy of < 1 mm, tracking with < 50 s intervals was necessary. Conclusions: For ultra-hypofractionated radiotherapy of the prostate with treatment times > 2.5 min, intrafraction motion management is recommended. [ABSTRACT FROM AUTHOR]

Node-positive prostate cancer is a difficult clinical scenario without clear guidelines regarding postoperative management. We identified 336 men with node-positive prostate cancer treated at a single center with or without postoperative radiation therapy in order to develop nomograms predictive of metastasis and death. These models can discretely quantify an individual's risk of metastasis or death with and without postprostatectomy radiotherapy. Purpose/Objectives: We aimed to develop nomograms to predict the risk reduction for metastasis and death in pathologically node-positive (pN +) prostate cancer patients treated with or without radiation therapy (RT). Materials/Methods: From a prospectively gathered institutional database, we identified patients with pN + M0 prostate cancer after surgery. We evaluated several regression models of known or suspected clinical-pathologic covariates and selected the model with the highest Harrell's concordance-index (c-index) and clinical utility to prognosticate metastasis for inclusion in a nomogram. Covariates in the final, competing-risk adjusted, metastasis model included PSA nadir after surgery, pathologic T-stage, margin status, Gleason score (GS), number of positive lymph nodes, and use of postoperative radiotherapy combined with androgen deprivation therapy (RT + ADT). The overall survival model also included Charlson comorbidity score and age. Results: 336 pN + men with a mean age of 64.9 years and a median follow-up of 4.1 years who had a radical prostatectomy were included in the analysis. 83 men were recommended RT + ADT, of whom 4% refused the ADT and received RT alone. C-index was 0.85 and 0.71 for the MFS and OS models, respectively. On multivariable analysis (MVA) adjusted for competing risks, RT + ADT significantly improved MFS (HR = 0.70 P = < .01) with number of nodes positive, GS 8-10, PSA nadir > 1 ng/mL, and pT3b prognostic for metastasis. MVA for OS demonstrates RT + ADT improves survival (HR = 0.40, P = .02), with GS8-10 and PSA nadir > 1.0 prognostic for death. Conclusion: We developed predictive nomograms for patients with pN + prostate cancer following radical prostatectomy. These models can discretely quantify an individual's risk of metastasis or death with and without postprostatectomy radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction: during radiotherapy, interfractional and intrafractional anatomic variations in pelvic organs may be observed. The purpose of this study is to evaluate these variations in patients with prostate cancer receiving intensity-modulated radiotherapy (IMRT). Methods: ten patients were enrolled in this study. Five weekly dosimetry scans were performed with delineation of prostate and pelvic organs (bladder and rectum). Volumetric variations of these three organs as well as prostate isocenter shift along the three axes of space (X, Y, Z) were recorded. Results: a significant mean decrease in prostate volume of 18.82% ± 3.87% (p= 0.008) was found at the end of treatment. Significant and random volumetric variations were detected in organs at risk with a higher amplitude at the level of the bladder compared to those of the rectum (-90.17 cc ± 151.56 cc and -23.90 cc ± 35.42 cc, respectively). Changes in rectal volume were correlated with prostate isocenter shift along the Y and Z axes, with an average migration of +1.90 mm ± 3,36 mm and -0.78 mm ± 1,21 mm, respectively. Conclusion: volumetric variation of the rectum in patients with prostate cancers receiving IMRT was accompanied by a significant displacement of the prostate along the Y and Z axes, which could cause partial deviation of the initially established prostate volume. [ABSTRACT FROM AUTHOR]

Background/Aim: In prostate cancer, postoperative radiotherapy timing is debated to avoid overtreatments and toxicities. This study compared acute and late rectal and bladder toxicities in the adjuvant and salvage setting. Patients and Methods: In total, 129 patients were analyzed in two groups: adjuvant radiotherapy (aRT) and salvage radiotherapy (sRT). Results: In aRT and sRT, grade 1 (G1) acute bladder toxicities were detected in 40 and 30 patients, and grade 2 (G2) in 1 and 6; G1 late bladder toxicities were described in 30 and 20, and G2 in 6 and 2, respectively. In aRT and sRT, acute G1 rectal toxicities were reported in 18 and 27 patients, and G2 in 5 and 4, respectively. Late rectal G1 toxicities were observed in 10 patients, G2 in 6 and G3 in 1 in the aRT. In sRT, 8 patients and 1 developed G1 and G2 toxicities, respectively. Regarding bladder toxicity, a higher incidence occurred in aRT; late toxicity was lower in sRT. Conclusion: Adjuvant and salvage RT in prostate cancer treatment resulted in acceptable toxicities. [ABSTRACT FROM AUTHOR]

Background/Aim: We investigated the changes in and characteristics of renal function in Japanese patients with highrisk prostate cancer (PCa) who underwent radiotherapy and long-term androgen deprivation therapy (ADT), including those seen after the ADT was discontinued. Patients and Methods: Among 60 patients who were pathologically diagnosed with PCa and received ADT for 24 months and radiotherapy, 36 patients who underwent treatment for stage B or C PCa were eligible. We assessed renal function using the estimated glomerular filtration rate (eGFR) and investigated the rate of change in the eGFR (ΔeGFR) during and after ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction at 36 months. Results: The incidence of renal dysfunction at 36 months was 75% (27/36). Multivariate analysis showed that the presence/absence of HF was an independent predictor of renal dysfunction at 36 months. Conclusion: Renal function tended to recover after ADT was received for 24 months and subsequently discontinued. The presence/absence of HF represents new and meaningful information for patients receiving ADT, and highrisk PCa patients prior to ADT. [ABSTRACT FROM AUTHOR]

Background/Aim: To evaluate the clinical outcomes of men with prostate cancer (PCa) submitted to hydrogel spacer injection before hypofractionated radiotherapy (HRT). Patients and Methods: From April 2018 to April 2020, 32 patients with clinically localized PCa underwent hydrogel injection Space OAR before HRT to the prostate and seminal vesicle; the prescription dose was 60 Gy in 20 fractions, 5 days/week over 4 weeks. PSA levels, genitourinary (GU) and gastrointestinal (GI) toxicities, and sexual function were prospectively evaluated. Results: PSA levels at the median follow up of 15 months was 0.52 ng/ml; 28.1% vs. 78.1% patients had GI vs. GU Grade 0 acute toxicity and 93.7% vs. 0% had GI vs. GU Grade 0 late toxicity. Furthermore, 88.1% of patients kept pretreatment sexual potency. Conclusion: The use of the hydrogel Spacer OAR before HRT is useful for reducing acute and late GU and GI toxicities. [ABSTRACT FROM AUTHOR]

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5–87.5% of cases); presentation to multidisciplinary tumour board (2.5–100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42–102.5 days); number of treatment interruptions ≥ 1 day (7.5–97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures. [ABSTRACT FROM AUTHOR]

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions. [ABSTRACT FROM AUTHOR]

The prostate is a hormone-responsive organ where testicular androgens drive the proliferation and survival of prostatic cells, ensuring the development and functioning of this gland throughout life. Androgen deprivation therapy leads to apoptosis of prostatic cells and organ regression, and is a cornerstone of prostate cancer and benign prostatic hypertrophy treatment. For several decades, androgen deprivation has been used as an adjuvant to external beam radiotherapy, however, emerging data suggests that the low rates of epithelial proliferation in the castrated prostate imparts radio-resistance. As proliferating cells exhibit increased sensitivity to radiation, we hypothesized that short bursts of synchronized epithelial proliferation, which can be achieved by exogeneous testosterone supplementation prior to targeted high-dose radiation, would maximize sustained prostate ablation, while minimizing damage to surrounding tissues. To test this hypothesis, we designed a novel computed-tomography (CT)-guided stereotactic prostate radiation therapy (CT-SPRT) technique to deliver a single high-dose 25 Gy fraction of X-ray radiation. Sustained prostatic cell ablation was assessed post CT-SPRT by measuring prostate weight, epithelial cell number, and relative contributions of luminal and basal epithelial populations in control and testosterone-pretreated glands. CT-SPRT was safely delivered with no observed damage to surrounding rectal and bladder tissues. Importantly, castrated mice that received a pulse of testosterone to induce synchronous cell proliferation prior to CT-SPRT exhibited significant sustained gland ablation compared to control mice. These results provide new insights in stereotactic radiotherapy sensitivity to maximize prostatic cell ablation and improve our understanding of prostate gland regeneration that can potentially lead to improved non-invasive therapies for benign prostatic hypertrophy and prostate cancer. [ABSTRACT FROM AUTHOR]

La consultation annuelle de suivi après la radiothérapie d'un cancer de la prostate se résume en un entretien oral avec un oncologue radiothérapeute. L'objectif de ce travail était de sonder la population cible sur ses connaissances et perceptions de la téléconsultation. Une étude prospective a été menée à l'Institut de cancérologie Lucien Neuwirth chez les patients en cours de traitement ou de suivi au cours du printemps 2019 (n = 158). Un autoquestionnaire a été élaboré pour les besoins de l'étude. La satisfaction et l'enthousiasme du patient ont été évalués à l'aide d'une échelle visuelle analogique (de 0/10 à 10/10). Cent cinquante-huit patients ont accepté de répondre à l'enquête. La quasi-totalité de la population utilisait le téléphone comme moyen de communication et 56 % des patients disposaient d'une connexion internet. Environ 56 % des patients affirmaient avoir des notions sur la téléconsultation, sans n'avoir jamais eu recours à ce dispositif. Si 60,8 % des patients ne seraient pas opposés à une proposition de téléconsultation avec un enthousiasme d'EVA (Échelle visuelle analogique) médiane de 6/10, les avis étaient partagés concernant le mode surveillance : 48,7 % souhaitaient conserver une surveillance classique et 48,7 % envisageaient d'alterner entre consultation présentielle et téléconsultation. Cette enquête de faisabilité menée sur une population de seniors montre que la téléconsultation est une option envisageable pour le suivi après la radiothérapie du cancer de la prostate, même si un travail d'information et d'éducation thérapeutique sera nécessaire pour encadrer cette nouvelle pratique. The annual follow-up in radiotherapy for prostate cancer consists of an oral interview with a radiation oncologist. The present study aimed at surveying the target population on their knowledge and perceptions of telemedicine. A prospective study was conducted at the Lucien Neuwirth Cancer Institute (France) that included patients with prostate cancer undergoing treatment or in follow-up, during spring 2019 (n = 158). A specific questionnaire was designed for the study. Patient's self-evaluation of satisfaction and enthusiasm was assessed through visual analog scale (VAS) (0/10 to 10/10). One hundred and fifty-eight patients completed the survey. The vast majority of the population commonly used phone for communication and 56% of patients owned internet connexion. Around 56% of patients declared telemedicine knowledge without having ever experienced telemedicine. If 60.8% of patients would not be against telemedicine with a median enthusiasm VAS of 6/10, patients' opinions were divergent: 48.7% of patients would like to keep a classical follow-up and 48.7% of patients would envision to alternate classical consultation with telemedicine. This feasibility study with an aged cohort showed that telemedicine is a valuable option for long-term radiotherapy follow-up, even if therapeutic education and information will be necessary to supervise this novel approach. [ABSTRACT FROM AUTHOR]

Background/Aim: We examined the prognostic value of intraprostatic gross tumour volume (GTV) as measured by multiparametric MRI (mpMRI) in patients with prostate cancer following (primary) external beam radiation therapy (EBRT). Patients and Methods: In a retrospective monocentric study, we analysed patients with prostate cancer (PCa) after EBRT. GTV was delineated in pre-treatment mpMRI (GTV-MRI) using T2-weighted images. Coxregression analyses were performed considering biochemical failure recurrence-free survival (BRFS) as outcome variable. Results: Among 131 patients, after a median follow-up of 57 months, biochemical failure occurred in 27 (21%). GTV-MRI was not correlated with % of positive biopsy cores, Gleason score and initial PSA (all r<0.2) and only moderately correlated with cT stage (r=0.32). In univariate analysis, cT stage, Gleason score and GTV-MRI were higher in subjects with shorter BRFS (p<0.05). GTV-MRI remained a significant predictor for BRFS in multivariate analyses, independent of Gleason score and cT stage. Conclusion: GTV, defined using mpMRI, provides incremental prognostic value for BRFS, independent of established risk factors. This supports the implementation of imaging-based GTV for riskstratification, although further validation is needed. [ABSTRACT FROM AUTHOR]

Background/Aim: In percutaneous radiotherapy dose-distribution and volumetric-load of normal tissue varies in different radiation-techniques. Haematotoxicity may lead to deficiencies of the immune and blood system or to secondary malignancies. Therefore, regular blood-counts are carried out during fractionated radiotherapy. The aim was to investigate patient haemogram courses during radiotherapy of localised prostate-cancer treated with different radiationtechniques (n=3). Patients and Methods: In this prospective study, blood count changes were examined during fractionated radiotherapy (3D-conformal-RT/step-and-shootIMRT/helical-IMRT) on the prostate-region in localised prostate-cancer cases (n=50). Results: The whole patient group displayed a small but significant reduction in leukocytes. This reduction was higher in the two IMRT groups compared to the 3D-group but without any case of leukopenia. Haemoglobin- or thrombocyte-levels did not significantly change. Conclusion: Regardless of the delivery mode used, localised fractionated irradiation of prostate region did not cause any clinically relevant haemogram changes in this study. These findings question the necessity of regular blood counts during fractionated radiotherapy of the prostate region for patients without any risk factors. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the dose-volume histogram parameters for late hematuria and rectal hemorrhage in patients receiving radiotherapy after radical prostatectomy. Patients and Methods: Data of 86 patients treated between January 2006 and June 2019 were retrospectively evaluated. The median radiation dose was 64 Gy in 32 fractions. Receiver operating characteristic (ROC) curves were used to identify optimal cut-off values for late adverse events. Results: Eleven patients experienced hematuria, and the 5-year cumulative rate was 18%. Four patients experienced rectal hemorrhage, and the 5-year cumulative rate was 7%. ROC curve analysis demonstrated the following significant cut-off values: bladder V50 Gy: 43% (p=0.02) and V40 Gy: 50% (p=0.03) for hematuria, and rectum V60 Gy: 13% (p=0.04) and V50 Gy: 33% (p=0.03) for rectal hemorrhage. Conclusion: This is the first study to identify dose constraints that may reduce hematuria and rectal hemorrhage in patients receiving radiotherapy in the postoperative setting. [ABSTRACT FROM AUTHOR]

Background/Aim: To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. Patients and Methods: Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. Results: A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate- and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p<0.01). Conclusion: Dose escalation to >74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage. [ABSTRACT FROM AUTHOR]

Abstract Background To assess multiparametric magnetic resonance imaging (mpMRI) characteristics in prostate cancer (PCa) before and after irreversible electroporation (IRE) and to investigate their correlation with the presence of post-operative recurrence of PCa. Methods MpMRI was performed in 30 men with PCa prior to treatment, after 10 days and at 6 months. An additional scan at 1 year was available for 18 men. Two radiologists assessed retrospectively the following parameters by planimetry: tumour volume, necrotic volume (early post-treatment scan) and residual fibrosis. Residual tumour/recurrence were defined as a suspicious area within the treatment field scored ≥ 4 on a 1-to-5 scale. Oncological outcome was also assessed. Results The median follow-up of the entire study was 16 months. Six men were undertreated and showed mpMRI recurrence after 6 months. At 1-year, three additional men had recurrence. Overall, four of these 9 men (44%) were retreated. The other five men did not receive any further treatment. Median time to re-treatment was 15 months. Median pre-treatment lesion volume was 0.65 cc, 0.66 cc and 0.43 cc on the different mpMRI sequences (T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging). Median necrotic volume was 10.77 cc. Median overall residual fibrosis volumes were 0.84 cc and 0.95 cc at 6-month and 1-year mpMRI. Pre-treatment, necrotic and residual fibrosis volumes were significantly different (p < 0.001). Pre-treatment tumour volumes on diffusion-weighted imaging and necrotic volumes were correlated (r = 0.18; p = 0.02). Conclusions MpMRI is able to visualise the IRE ablation effects in men with PCa. MpMRI-derived parameters - such as tumour, necrotic and fibrosis volumes - can be measured and are potentially useful for assessing efficacy in the medium term, as with other ablative techniques. [ABSTRACT FROM AUTHOR]

Purpose: Retrospective analyses of cancer registry and institutional data have consistently found better survival after radical prostatectomy versus radiation therapy, which contrasts with findings from a randomized trial. This is likely because of the inability of retrospective studies to fully account for comorbidity differences across treatment groups because of the lack of detailed data in the registries. We use a unique population-based data set with detailed data regarding comorbidities and functional limitations to assess whether this can provide valid comparisons of survival across prostate cancer treatment groups.Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) data set results from a linkage between the SEER database and the MHOS database, which includes detailed information regarding patient-reported comorbidity and functional limitations. We analyzed 3102 patients with prostate cancer in SEER-MHOS and used latent class analysis to identify the healthiest group with minimal comorbidity burden and functional limitations. Among the healthiest group, we examined overall survival across treatments using the Kaplan-Meier method.Results: Three distinct health groups were identified using latent class analysis; the healthiest group comprised 57% of the cohort and had a 10-year overall survival of 67%. Other health groups had higher rates of comorbidities or functional limitations. Among the healthiest group, 10-year overall survival differed across treatment groups: no local treatment (55%), external beam radiation therapy (69%), brachytherapy (76%), and radical prostatectomy (85%). Survival curves for the 3 treated groups separated at 4 years of follow-up.Conclusions: Despite the detailed health status information available in SEER-MHOS, our retrospective analysis could not fully account for patient selection biases across prostate cancer treatment groups. These findings highlight an important limitation of retrospective studies using population-based data sets and serve as a reminder to interpret results with caution. [ABSTRACT FROM AUTHOR]

Abstract The purpose of this case study is to develop a method to account for the difference in the daily volumes in the bladder, rectum, and targets in prostate radiotherapy and to compare the predicted dose to the actual dose to these organs. Five patients, both prospectively and retrospectively, were selected from 2 different cancer centers, with a biopsy-confirmed diagnosis of prostate cancer. The patients' planning target volume (PTV) and organs at risk (OAR) were contoured on the computed tomography (CT) dataset using either Eclipse or Monaco treatment planning systems (TPSs). Cone-beam computed tomography (CBCT) scans were collected before each daily treatment and exported to MIM software for analysis. The automatically generated reports evaluated the organ volume changes, the actual dose received during a single fraction, and the projected dose to each organ at the completion of the treatment course via comparative cumulative dose-volume histograms (DVHs). Volume changes in the bladder and rectum can cause notable variations in the prescribed dose vs the actual dose received. MIM software was proven to have utility prospectively by tabulating daily dose and projecting final doses, potentially aiding physicians in decisions about the boost plans, thus making offline adaptive radiation therapy (ART) clinically manageable. [ABSTRACT FROM AUTHOR]

Background and purpose: In prostate cancer treatment with external beam radiation therapy (EBRT), prostate motion and internal changes in tissue distribution can lead to a decrease in plan quality. In most currently used planning methods, the uncertainties due to prostate motion are compensated by irradiating a larger treatment volume. However, this could cause underdosage of the treatment volume and overdosage of the organs at risk (OARs). To reduce this problem, in this proof of principle study we developed and evaluated a novel adaptive planning method. The strategy proposed corrects the dose delivered by each beam according to the actual position of the target in order to produce a final dose distribution dosimetrically as similar as possible to the prescribed one. Material and methods: Our adaptive planning method was tested on a phantom case and on a clinical case. For the first, a pilot study was performed on an in-silico pelvic phantom. A “library” of intensity modulated RT (IMRT) plans corresponding to possible positions of the prostate during a treatment fraction was generated at planning stage. Then a 3D random walk model was used to simulate possible displacements of the prostate during the treatment fraction. At treatment stage, at the end of each beam, based on the current position of the target, the beam from the library of plans, which could reproduce the best approximation of the prescribed dose distribution, was selected and delivered. In the clinical case, the same approach was used on two prostate cancer patients: for the first a tissue deformation was simulated in-silico and for the second a cone beam CT (CBCT) taken during the treatment was used to simulate an intra-fraction change. Then, dosimetric comparisons with the standard treatment plan and, for the second patient, also with an isocenter shift correction, were performed. Results: For the phantom case, the plan generated using the adaptive planning method was able to meet all the dosimetric requirements and to correct for a misdosage of 13% of the dose prescription on the prostate. For the first clinical case, the standard planning method caused underdosage of the seminal vesicles, respectively by 5% and 4% of the prescribed dose, when the position changes for the target were correctly taken into account. The proposed adaptive planning method corrected any possible missed target coverage, reducing at the same time the dose on the OARs. For the second clinical case, both with the standard planning strategy and with the isocenter shift correction target coverage was significantly worsened (in particular uniformity) and some organs exceeded some toxicity objectives. While with our approach, the most uniform coverage for the target was produced and systematically the lowest toxicity values for the organs at risk were achieved. Conclusions: In our proof of principle study, the adaptive planning method performed better than the standard planning and the isocenter shift methods for prostate EBRT. It improved the coverage of the treatment volumes and lowered the dose to the OARs. This planning method is particularly promising for hypofractionated IMRT treatments in which a higher precision and control on dose deposition are needed. Further studies will be performed to test more extensively the proposed adaptive planning method and to evaluate it at a full clinical level. [ABSTRACT FROM AUTHOR]

Background: To compare WBC counts during treatment of localized prostate cancer with either conventionally fractionated (CF) or moderately hypofractionated (HYPO) radiotherapy.Methods: Weekly blood test results were extracted from the charts of patients treated within a phase III study comparing HYPO to CF. In order to compare WBC counts at the same nominal dose in both arms and thus to tease out the effect of fractionation, for each recorded WBC value the corresponding cumulative total dose was extracted as well. WBC counts were binned according to percentiles of the delivered dose and three dose levels were identified at median doses of 16, 34.1 and 52 Gy, respectively. A General Linear Model based on mixed design Analysis Of Variance (ANOVA) was used to test variation of WBC counts between the two treatment arms.Results: Out of 168 randomized patients, 140 (83.3%) had at least one observation for each one of the selected dose levels and were included in the analysis. Mean counts were lower in the CF than the HYPO arm at all selected dose levels, reaching a statistically significant difference at dose level #3 (5397/mm3 vs 6038/mm3 for CF and HYPO, respectively, p = 0.004). The GLM model confirms that the impact of dose on WBC counts is significantly lower in the HYPO arm over the CF one (Greenhouse-Geisser test, p = 0.04). Interestingly, while WBC counts tend to drop throughout all dose levels in the CF arm, this is the case only in the earlier part of treatment in the HYPO arm.Conclusion: This secondary analysis of a phase III study shows that dose fractionation is correlated to WBC drop during treatment of localized prostate cancer, favoring HYPO over CF. [ABSTRACT FROM AUTHOR]

Highlights • Quantitative Susceptibility Mapping generated positive contrast for brachytherapy seeds. • Seeds were differentiable from calcifications on magnetic susceptibility maps. • An unsupervised machine learning algorithm was developed for seed detection and localization. • The output of the proposed MRI-based workflow was in perfect agreement with the CT-based approach. Abstract Background and purpose Permanent seed brachytherapy is an established treatment option for localized prostate cancer. Currently, post-implant dosimetry is performed on CT images despite challenging target delineation due to limited soft tissue contrast. This work aims to develop an MRI-only workflow for post-implant dosimetry of prostate brachytherapy seeds. Material and methods A prostate mimicking phantom containing twenty stranded I-125 dummy seeds and calcifications was constructed. A three-dimensional gradient-echo MR sequence was employed on 3T and 1.5T MR scanners. An optimized quantitative susceptibility mapping (QSM) technique was applied to generate positive contrast for the seeds and calcifications. Seed numbers, centroids, and orientations were determined using unsupervised machine learning algorithms (K-means and K-medoids clustering). The geometrical seed positions and the resulting dose distribution were compared to the clinical CT-based approach. Results The optimized QSM-based method generated high quality positive contrast for the seeds that were significantly different from that for calcifications and could be easily differentiated by thresholding. The estimated seed centroids from both 3T and 1.5T MR data were in perfect agreement with the standard CT-based seed detection algorithm (maximum difference of 0.7 mm). The estimated seed orientations were highly correlated with the actual orientations (R > 0.98). Conclusions The proposed MRI-based workflow enabling an accurate and robust means to localize the seeds (position and orientation) upon validation on complex seed configurations, has the potential to replace the current widely practiced CT-based workflow. [ABSTRACT FROM AUTHOR]

Abstract Background and purpose To explore the use of texture analysis (TA) features of patients' 3D dose distributions to improve prediction modelling of treatment complication rates in prostate cancer radiotherapy. Material and methods Late toxicity scores, dose distributions, and non-treatment related (NTR) predictors for late toxicity, such as age and baseline symptoms, of 351 patients of the hypofractionation arm of the HYPRO randomized trial were used in this study. Apart from DVH parameters, also TA features of rectum and bladder 3D dose distributions were used for predictive modelling of gastrointestinal (GI) and genitourinary (GU) toxicities. Logistic Normal Tissue Complication Probability (NTCP) models were derived, using only NTR parameters, NTR + DVH, NTR + TA, and NTR + DVH + TA. Results For rectal bleeding, the area under the curve (AUC) for using only NTR parameters was 0.58, which increased to 0.68, and 0.73, when adding DVH or TA parameters respectively. For faecal incontinence, the AUC went up from 0.63 (NTR only), to 0.68 (+DVH) and 0.73 (+TA). For nocturia, adding TA features resulted in an AUC increase from 0.64 to 0.66, while no improvement was seen when including DVH parameters in the modelling. For urinary incontinence, the AUC improved from 0.68 to 0.71 (+DVH) and 0.73 (+TA). For GI, model improvements resulting from adding TA parameters to NTR instead of DVH were statistically significant (p < 0.04). Conclusion Inclusion of 3D dosimetric texture analysis features in predictive modelling of GI and GU toxicity rates in prostate cancer radiotherapy improved prediction performance, which was statistically significant for GI. [ABSTRACT FROM AUTHOR]

Highlights • PSA bounce after HDR-BT combined with external RT is common and associated with a good prognosis. • Younger age and lower Gleason score were associated with the occurrence of PSA bounce. • No association was found between prostate volume or concurrent GU symptoms and a PSA bounce. Abstract Background PSA kinetics after curative radiotherapy for prostate cancer is an important part of the posttreatment evaluation. We analysed PSA bounce occurrence after combined high dose rate brachytherapy (HDR-BT) and external radiotherapy (ERT). Material & methods We analysed 623 patients treated from 1995 to 2008. The median age was 66 years (47–79). The median initial PSA was 12 ng/ml (0.1–224). Neoadjuvant endocrine therapy was given to 429 patients. ERT was given with 2 Gy fractions to 50 Gy and HDR-BT in two 10 Gy fractions. The median follow-up was 11 years (range 2–266 months). PSA bounce was defined as a temporary rise in PSA >0.2 ng/ml. PSA failure was defined according to the Phoenix definition. Results PSA bounce occurred in 159 patients (26%), where 56 patients had a bounce amplitude >2 ng/ml and 31 patients had multiple bounces. Median time to bounce peak was 15 (3–103) months with a median bounce value of 1.5 (0.3–12) ng/ml. Younger age and lower Gleason scores were associated with PSA bounce. In a Cox regression analysis with PSA bounce as a time-dependent covariate and adjusted for other prognostic factors, PSA bounce was associated with a lower risk for PSA failure (HR = 0.42; 95% confidence interval 0.26–0.70). Conclusion PSA bounce after HDR-BT combined with ERT is common and associated with a good prognosis. As the relapse risk after an early bounce is very low, the findings should alert clinicians not to initiate salvage treatment too early. Research in prospective identification of PSA bounce is clinically relevant. [ABSTRACT FROM AUTHOR]

Abstract Purpose To describe toxicity, biochemical outcome and quality of life after MRI guided focal high dose rate brachytherapy (HDR-BT) in a single fraction of 19 Gy for localized prostate cancer. Materials and methods Between May 2013 and April 2016, 30 patients were treated by MRI-guided focal HDR-BT. Patients with visible tumour on MRI were included. All patients were ≥65 years, T-stage

Background: Investigating oncological outcomes in patients registered in the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) in terms of biochemical relapse-free survival (bRFS) by the Phoenix and the newly developed J-POPS definitions, exploration of predictive factors for bRFS, and preliminary verification of pitfalls of prostate-specific antigen (PSA) failure definitions.Methods: Between July 2005 and June 2007, 2316 clinically localized patients underwent permanent seed implantation. The primary endpoint was bRFS. One of the secondary endpoints was overall survival (OS).Results: The median age was 69 and performance status was 0 in 99.1% of participants. The median biologically effective dose (BED) was about 180 Gy2. During a median follow-up of 60.0 months, 8.4 and 5.9% had PSA failure by the Phoenix and the J-POPS definitions, respectively. The 5-year bRFSs based on the Phoenix and the J-POPS definitions were 89.1 and 91.6%, respectively. The 5-year OS was 97.3%. According to multivariate analyses, only age affected bRFS based on the Phoenix definition, whereas the risk group and BED independently affected bRFS based on the J-POPS definition. A spontaneous PSA decrease was seen in 91.1% of participants after PSA failure based on the Phoenix definition alone, but in only 22.2% after PSA failure based on the J-POPS definition alone.Conclusion: The world’s largest registration study, J-POPS, consisted of patients with longevity, and a highly quality-controlled BED resulted in excellent bRFS and OS. The high likelihood of PSA bounce by the Phoenix definition should be taken into account, especially in younger patients.Clinical trial information: NCT00534196. [ABSTRACT FROM AUTHOR]

Background: The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment.Methods: The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial.Findings: Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group.Interpretation: In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT.Funding: National Cancer Institute. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of late-stage prostate cancer by targeted radiotherapeutics such as 131I-MIP-1095 and 177Lu-PSMA-617 has shown encouraging early results. Lu-177 is preferred to I-131 in clinical settings, but targeted radioligand therapy (RLT) with 177Lu-PSMA-617 has not reached its full potential due to insufficient dose delivery to the tumor. We recently developed a dual-targeting radioiodinated ligand, RPS-027, that targets PSMA and uses albumin binding to enable good tumor uptake and significantly reduced kidney uptake in a preclinical model. Further development of this ligand is limited by the inability to independently modify PSMA and albumin binding and the requirement of I-131 for therapeutic application. We therefore sought to devise a new class of trifunctional ligands for RLT with (1) a high-affinity PSMA-binding domain, (2) an albumin-binding group (ABG), and (3) a chelator for radiometals such as 68Ga3+, 177Lu3+ and 225Ac3+.Methods: Ligands incorporating a triazolylphenylurea-containing PSMA-targeting group, an Nε-(2-(4-iodophenyl)acetyl)lysine ABG and the bifunctional chelator p-SCN-Bn-DOTA linked by a PEG-containing polymer containing 0,3,4,6,8 or 12 repeats were prepared. PSMA affinity was determined in LNCaP cells and uptake and tissue distribution was studied in mice bearing LNCaP tumor xenografts and compared to 177Lu-PSMA-617. Imaging studies were performed up to 24 h post-injection (p.i.) using 66Ga3+ and biodistribution studies at 4 h, 24 h and 96 h p.i. with 177Lu3+.Results: PSMA affinity was high (IC50 = 1-10 nM) and inversely proportional to the linker length. Tumor uptake correlated with binding affinity and was significantly greater than for 177Lu-PSMA-617 over 96 h. The highest uptake was achieved with 177Lu-RPS-063 (30.0 ± 6.9 %ID/g; 4 h p.i.). Kidney uptake was generally high, with the exception of the lowest affinity ligand 177Lu-RPS-067. Each of the compounds showed slower blood clearance than 177Lu-PSMA-617, with clearance proportional to linker length.Conclusions: The high tumor uptake achieved with these trifunctional ligands predicts larger (up to 4×) doses delivered to the tumor than can be achieved with 177Lu-PSMA-617. Although PSMA-mediated kidney uptake was also observed, the exceptional area under the curve (AUC) in the tumor warrants further investigation of these novel ligands as candidates for RLT. [ABSTRACT FROM AUTHOR]

Purpose: Hypofractionated radiotherapy of prostate cancer is gaining clinical acceptance given its potential increase in therapeutic ratio and evidence for noninferiority and lack of added late toxicities compared to conventional fractionation. However, concerns have been raised that smaller number of fractions might lead to larger dosimetric influence by interfractional motion. We aim to compare the effect of these variations on hypofractionated pencil beam scanning (PBS) proton therapy and volumetric modulated arc therapy (VMAT) for localized prostate cancer. Methods: Weekly CT images were acquired for 6 patients participating in a randomized clinical trial. PBS plans featuring bilateral (BL) and a combination of lateral and anterior‐oblique beams (AOL), and VMAT plans were created. All patients were treated to a conventional 79.2 Gy total dose in 44 fractions. For this study, hypofractionated dose to the prostate gland was 51.6 Gy in 12 fractions or 36.25 Gy in 5 fractions, and 32.8, and 23.1 Gy to proximal seminal vesicles, respectively. Patients were simulated with endorectal balloons to aid gland immobilization. Three fiducial markers were implanted for setup guidance. All plans were recomputed on the weekly CT images after aligning with the simulation CT. The entire set of 9 CT images was used for dose recalculation for 12‐fraction and only 5 used for the 5‐fraction case. Adaptive range adjustments were applied to anterior‐oblique beams assuming clinical availability of in vivo range verification. Fractional doses were summed using deformable dose accumulation to approximate the delivered dose. Biologically equivalent dose to 2 Gy(EQD2) was calculated assuming α/β of 1.5 Gy for prostate and 3 Gy for bladder and rectum. Results: The median delivered prostate D98 was 0.13/0.14/0.13 Gy(EQD2) smaller than planned for PBS‐BL, 0.13/0.27/0.17 Gy(EQD2) for PBS‐AOL and 0.59/0.66/0.59 Gy(EQD2) for VMAT, for 44/12/5 fractions, respectively. The largest D98 reduction was 1.5 and 3.5 Gy(EQD2) for CTV1 and CTV2, respectively. Target dose degradation was comparable for all fractionation schemes within each modality. The maximum increase in rectum D2 was 0.98 Gy(EQD2) for a 5‐fraction PBS case. Conclusions: The robustness of PBS and VMAT were comparable for all patients for the studied fractionations. The delivered target dose generally remained within clinical tolerance and the deviations were relatively minor for both fractionation schemes. The delivered OAR dose stayed in compliance with the RTOG hypofractionation constraints for all cases. [ABSTRACT FROM AUTHOR]

Purpose: To compare patient-reported disease-specific functional outcomes after external beam radiation therapy (EBRT) and EBRT combined with low-dose-rate brachytherapy prostate boost (EB-LDR) among men with localized prostate cancer.Methods and Materials: The prospective, population-based Comparative Effectiveness Analysis of Surgery and Radiation study enrolled men with localized prostate cancer in 2011 to 2012. The 26-item Expanded Prostate Cancer Index Composite measured patient-reported disease-specific function at baseline and at 6, 12, and 36 months. Higher domain scores indicate better function. Minimal clinically important difference was defined as 6 for urinary incontinence, 5 for urinary irritative function, 4 for bowel function, 12 for sexual function, and 4 for hormonal function. Multivariable linear and logistic regression models were fit to estimate the effect of treatment on patient-reported outcomes.Results: Five-hundred seventy-eight men received EBRT and 109 received EB-LDR. Median patient age was 69 years, and 70% had intermediate- or high-risk disease. Men in the EB-LDR group were younger (P < .001) and less likely to receive androgen deprivation therapy (P < .001). Baseline urinary, bowel, sexual, and hormonal function was similar between treatment groups (P > .05). On multivariable analyses, men receiving EB-LDR reported worse urinary irritative function at 6 months (adjusted mean difference [AMD] -14.4, P < .001), 12 months (AMD -12.9, P < .001), and 36 months (AMD -4.7, P = .034) than men receiving EBRT. At 12 months, men receiving EB-LDR reported worse bowel function (AMD -5.8, P = .002), but these differences were not seen at 36 months. There were no significant differences in sexual or hormone function between treatment groups.Conclusions: Men treated with EB-LDR report worse bowel function at 1 year and worse urinary irritative function through 3 years compared with men treated with EBRT alone. These side effect profiles should be discussed with patients when considering EB-LDR versus EBRT treatment. [ABSTRACT FROM AUTHOR]

Purpose: No prospective data examined the effect of radical prostatectomy (RP) vs. external beam radiotherapy (EBRT) in locally advanced prostate cancer (PCa). We aimed to compare survival outcomes of RP and EBRT in patients harboring cT3N0-1 PCa.Methods: Within the SEER database (2004-2014), we identified 5500 cT3N0-1 PCa patients. Cumulative incidence plots and competing-risks regression models (CRRs) tested cancer-specific mortality (CSM) and other cause of mortality (OCM) according to treatment type. The multivariable relationship between baseline prostate-specific antigen (PSA) values and 10-year CSM after either RP or EBRT was graphically depicted using the LOESS smoothing method. Sensitivity analyses were performed in cT3N0-only patients, after OCM propensity score matching, and through landmark analyses.Results: Ten-year CSM and OCM rates were significantly higher after EBRT (15.8 and 28.2%) than RP (8.1 and 10.4%) (all p < 0.0001). In multivariable CRRs, RP yielded lower CSM [hazard ratio (HR): 0.64] than EBRT. Significantly lower 10-year CSM rate was recorded after RP vs. EBRT through the entire range of baseline PSA values. The same results were recorded in cT3N0 subgroup, as well as after OCM propensity score matching. Finally, landmark analyses at 6, 12, 24, and 36 months rejected the effect of favorable survival bias after RP.Conclusions: CSM was significantly lower after RP than EBRT in cT3N0-1 PCa. A lower CSM was recorded throughout the entire range of baseline PSA and even in cT3N0 subgroup, as well as after OCM propensity score matching and landmark analyses. [ABSTRACT FROM AUTHOR]

Abstract: Prostate cancer (PCa) is one of the most common malignancies associated with bone metastases, and palliative radiation therapy (RT) is an effective treatment option. A total of 2641 patients were identified with PCa and bone metastases at diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as short course ([SC‐RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long course ([LC‐RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient characteristics were correlated with fractionation scheme using logistic regression. Overall survival was analyzed using the Kaplan‐Meier method, log‐rank test, Cox proportional hazards models, and propensity score‐matched analyses. A total of 2255 (85.4%) patients were included in the LC‐RT group and 386 (14.6%) patients in the SC‐RT group. SC‐RT was more common in patients over 75 years age (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32‐2.20), treatment at an academic center (OR: 1.76, 1.20‐2.57), living greater than 15 miles distance to treatment facility (OR: 1.38, 1.05‐1.83), treatment to the rib (OR: 2.99, 1.36‐6.60), and in 2014 (OR: 1.73, 1.19‐2.51). RT to the spine was more commonly long course (P < .0001). In the propensity‐matched cohort, LC‐RT was associated with improved OS (P < .0001), but no OS difference was observed between 37.5 Gy and either 8 Gy in one fraction or 20 Gy in 5 fractions (P > .5). LC‐RT remains the most common treatment fractionation scheme for palliative bone metastases in PCa patients. Use of palliative SC‐RT is increasing, particularly in more recent years, for older patients, treatment at academic centers, and with increasing distance from a treatment center. [ABSTRACT FROM AUTHOR]

Purpose: This observational study investigates the influence of interfractional motion on clinical target volume (CTV) coverage, planning target volume (PTV) margins, and rectum tissue sparing in carbon ion radiation therapy (CIRT). It reports dose coverage to target structures and organs at risk in the presence of interfractional motion, investigates rectal tissue sparing, and provides recommendations for lowering the rate of toxicity. We also propose probabilistic DVH based on cone-beam computed tomography (CBCT) table shifts from photon therapy for consideration in bone-matching CIRT treatment planning to represent probable dose to our CIRT patient population. Methods: At Gunma University Hospital intensity-modulated x-ray therapy (IMXT, aka IMRT) prostate cancer patients are positioned on a table which is shifted twice based on CBCT to align bones and then align prostate tissue to isocenter. These shifts thereby contain interfractional motion. A total of 1306 such table shifts from 85 patients were collected. Normal probability distributions were fit to the difference between bone-matching and prostate-matching CBCT-to-planning CT table shifts (i.e. interfractional motion). Between 2011 and 2016 CIRT prostate patients were treated with three beams to PTV1 (lateral-opposing and anterior) one per day for 9 fractions and two beams for a boost PTV2 (lateral-opposing) one per day for 7 fractions for a prescribed total of 57.6 Gy(RBE) as follows: PTV1 extends the prostate contour by 10/10, 5/10, 6/6 mm in the right/left, posterior/anterior, and superior/inferior directions, respectively, and the proximal seminal vesicles contour by 5 mm superiorly and inferiorly, 3 mm right and left. PTV2 reduces PTV1 posteriorly along a straight line to exclude the rectum and reduces the superior and inferior margins by 6 mm. Probable interfractional motion for 40 patients was simulated using each patient’s own beam data as follows: The previously fit normal probability distributions were randomly sampled 2000 times per patient, and the five beams were shifted and summed with the same relative weighting as in the 16-fraction regimen. The resulting dose distribution was then scaled back down by 16/2000 to match the prescribed number of fractions. We then analyzed the resulting doses to contoured structures. Results: Probable dose to rectum is substantially less than planned: For example, mean+-standard deviation D2% for planned and probable DVH is 51+-1.9 and 45+-2.4, respectively. Cumulative DVH show mean CTV fraction receiving a given probable dose is less than the mean fraction receiving the corresponding planned dose for doses larger than 52 Gy(RBE), up to 19% less at 57.4 Gy(RBE). Our PTV1 margins generally cover 95% of interfractional motion but seminal vesicles and inferior prostate receive less dose than planned due to insufficient PTV2 margins. Conclusion: Assuming rigidly shifting interfractional motion around the prostate region and neglecting minor changes in soft tissue stopping power, interfractional motion resulted in target underdosing but better tissue sparing in all cases. Given our low rates of relapse and recurrence, it appears less curative dose is needed than previously thought or else current planning target margins may be excessive: Planning target volumes should be reconsidered with the adoption of dose verification methods. Our probable dose distributions quantify expected dose for future dose verification studies. [ABSTRACT FROM AUTHOR]

Objective: To explore whether TachoSil, a hemostatic patch, can reduce the incidence of lymphocele formation. Development of a lymphocele is a frequent complication after pelvic lymph node dissection (PLND) for nodal staging in prostate cancer.Materials and Methods: From 2013 to 2017, 100 patients with prostate cancer who were set to undergo a staging PLND before external beam radiotherapy (n = 50) or PLND concomitant with radical prostatectomy (RP) (n = 50) were prospectively randomized 1:1 between bilateral TachoSil placement or nonplacement. Primary end points were radiographic lymphocele development, lymphocele volume (1 week and 1 month postoperatively), and the duration and volume of postoperative catheter drainage.Results: Patient, tumor, and surgical characteristics of the TachoSil and the control groups did not differ significantly. In total, 65 patients (65%) experienced a radiographic lymphocele up to 3 months after surgery: 29 (58%) in the TachoSil group and 36 (72%) in the control group (P = .34). Significantly less radiographic lymphoceles were observed 1 week postoperatively for patients who underwent sole PLND and 1 month postoperatively for patients who underwent PLND with RP in the TachoSil group compared with the control group (16% vs 48%, P = .024, and 24% vs 52%, P = .047, respectively). The other postoperative characteristics presented no significant differences between the 2 groups, neither for patients undergoing sole PLND nor for patients undergoing PLND with RP.Conclusion: Patients undergoing bilateral TachoSil placement after PLND seem less likely to develop a radiographic lymphocele early postoperatively. Nevertheless, the clinical relevance of the use of TachoSil remains highly debatable. [ABSTRACT FROM AUTHOR]

Purpose: In situ drug release concurrent with radiation therapy has been proposed to enhance the therapeutic ratio of permanent prostate brachytherapy. Both brachytherapy sources and brachytherapy spacers have been proposed as potential eluters to release compounds, such as nanoparticles or chemotherapeutic agents. The relative effectiveness of the approaches has not been compared yet. This work models the physical dose enhancement of implantable eluters in conjunction with brachytherapy to determine which delivery mechanism provides greatest opportunity to enhance the therapeutic ratio. Materials and methods: The combined effect of implanted eluters and radioactive sources were modeled in a manner that allowed the comparison of the relative effectiveness of different types of implantable eluters over a range of parameters. Prostate geometry, source, and spacer positions were extracted from treatment plans used for 125I permanent prostate implants. Compound concentrations were calculated using steady‐state solution to the diffusion equation including an elimination term characterized by the diffusion‐elimination modulus (ϕb). Does enhancement was assumed to be dependent on compound concentration up to a saturation concentration (csat). Equivalent uniform dose (EUD) was used as an objective to determine the optimal configuration of eluters for a range of diffusion‐elimination moduli, concentrations, and number of eluters. The compound delivery vehicle that produced the greatest enhanced dose was tallied for points in parameter space mentioned to determine the conditions under whether there are situations where one approach is preferable to the other. Results: The enhanced effect of implanted eluters was calculated for prostate volumes from 14 to 45 cm3, ϕb from 0.01 to 4 mm−1, csat from 0.05 to 7.5 times the steady‐state compound concentration released from the surface of the eluter. The number of used eluters (ne) was simulated from 10 to 60 eluters. For the region of (csat, Φ)‐space that results in a large fraction of the gland being maximally sensitized, compound eluting spacers or sources produce equal increase in EUD. In the majority of the remaining (csat, Φ)‐space, eluting spacers result in a greater EUD than sources even where sources often produce greater maximal physical dose enhancement. Placing eluting implants in planned locations throughout the prostate results in even greater enhancement than using only source or spacer locations. Conclusions: Eluting brachytherapy spacers offer an opportunity to increase EUD during the routine brachytherapy process. Incorporating additional needle placements permits compound eluting spacer placement independent of source placement and thereby allowing a further increase in the therapeutic ratio. Additional work is needed to understand the in vivo spatial distribution of compound around eluters, and to incorporate time dependence of both compound release and radiation dose. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS).Methods: A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders.Results: There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21).Conclusions: The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018;124:2939-47. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity.Methods and Materials: The study design was retrospective, with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiation therapy with curative intent, and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis, or mucus) were related to freedom from late biochemical failure (FFBF; nadir + 2). The validation cohort was from two separate institutions.Results: In all, 503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage had a longer FFBF on both univariate (hazard ratio [HR] 0.37; P = .004) and multivariate (HR 0.45; P = .035) analysis. The impact of acute toxicity on late FFBF seemed to be greater in patients treated with androgen deprivation (HR 0.19) than in those without (HR 0.48).Conclusion: Patients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiation therapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity. [ABSTRACT FROM AUTHOR]

Purpose: Data on prostate cancer (PCa) treatment in Africa remains under-reported. We present a review of the management of PCa at the cancer center of the largest tertiary referral facility in Ghana, with emphasis on curative treatment. Methods: We retrospectively reviewed data on 1,074 patients seen at the National Center for Radiotherapy and Nuclear Medicine from 2003 to 2016. Patient and disease characteristics at presentation are presented using descriptive statistics. The χ2 and Fisher’s exact tests and Mann-Whitney U test were used to analyze differences between categorical and continuous variables, respectively. Methods of survival analysis were used to evaluate the relative risk of biochemical disease-free survival (bDFS). Results: Seventy percent of the study population presented with localized disease. High-risk disease presentation accounted for 64.4% of these patients. Only 57.6% of patients with localized disease received curative radiotherapy. The 5-year overall survival for the curative cohort was 96% (interquartile range, 93% to 98%). The 5-year bDFS rates for low-, intermediate-, and high-risk groups were 95%, 70%, and 48%, respectively. Both Gleason score and pretreatment prostate-specific antigen were significant predictors for bDFS in multivariable analysis. Conclusion: We show that the majority of patients with PCa have locally advanced disease at the time of presentation for radiotherapy. bDFS was significantly better for low- and intermediate-risk than for high-risk disease. These data emphasize the dire need to re-evaluate screening and patient education of PCa in regions of the world with high incidence and mortality as well as the need for improved access to care and treatment delivery. [ABSTRACT FROM AUTHOR]

Background Whether prostate cancer severity modifies patient-reported functional outcomes after radical prostatectomy (RP) or external beam radiotherapy (EBRT) for localized cancer is unknown. Objective The purpose of this study was to determine whether differences in predicted function over time between RP and EBRT varied by risk group. Design, setting, and participants The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study that enrolled men with localized prostate cancer in 2011–2012. Among 2117 CEASAR participants who underwent RP or EBRT, 817 had low-risk, 902 intermediate-risk, and 398 high-risk disease. Outcome measurements and statistical analysis Patient-reported, disease-specific function was measured using the 26-item Expanded Prostate Index Composite (at baseline and 6, 12, and 36 mo). Predicted function was estimated using regression models and compared by disease risk. Results and limitations Low-risk EBRT patients reported 3-yr sexual function scores 12 points higher than those of low-risk RP patients (RP, 39 points [95% confidence interval {CI}, 37–42] vs EBRT, 52 points [95% CI, 47–56]; p < 0.001). The difference in 3-yr scores for high-risk patients was not clinically significant (RP, 32 points [95% CI, 28–35] vs EBRT, 38 points [95% CI, 33–42]; p = 0.03). However, when using a commonly used binary definition of sexual function (erections firm enough for intercourse), no major differences were noted between RP and EBRT at 3 yr across low-, intermediate-, and high-risk disease strata. No clinically significant interactive effects between treatment and cancer severity were observed for incontinence, bowel, irritative voiding, and hormone domains. The primary limitation is the lack of firmly established thresholds for clinically significant differences in Expanded Prostate Index Composite domain scores. Conclusions For men with low-risk prostate cancer, EBRT was associated with higher sexual function scores at 3 yr than RP; however, for men with high-risk prostate cancer, no clinically significant difference was noted. Men with high-risk prostate cancer should be counseled that EBRT and RP carry similar sexual function outcomes at 3 yr. Patient summary In this report, we studied the urinary, sexual, bowel, and hormonal functions of patients 3 yr after undergoing prostate cancer surgery or radiation. We found that for patients with high-risk disease, sexual function was similar between surgery and radiation. We conclude that high-risk patients undergoing radiation therapy should be counseled that sexual function may not be as good as low-risk patients undergoing radiation. [ABSTRACT FROM AUTHOR]

Radical treatment of localised prostate cancer is recognised to be an unnecessary intervention or overtreatment in many men. Consequently, there has been a rapid uptake in the use of focal ablative therapies. However, there are several biological and practical concerns about such approaches as they have yet to be proved as robust treatment options. In particular, the multifocal nature of prostate cancer argues against unifocal treatment, while limitations in imaging can preclude the accurate identification of the number, location, and extent of prostate cancer foci. To date, a number of ablative options have reported results on mainly low-risk disease. Most series are relatively immature, with a lack of consistent follow-up, and the morbidity of retreatment is often not considered. The authors consider focal therapy to be an investigational modality, and encourage prospective recording of outcomes and recruitment of suitable patients. Patient summary Focal therapy of prostate cancer is the targeted destruction of cancer within a specific part of the prostate gland, sparing the rest of the prostate and nearby tissue. This procedure could potentially reduce side effects when compared with established standard treatments, such as surgery or radiotherapy, which treat the entire prostate. Studies show that for most men with low-risk cancer, active surveillance is the preferred treatment option. However, the available data regarding all forms of focal therapy are still poor and inconclusive. Consequently, due to both the lack of clear results associated with focal therapy and the difficulties in detecting all cancerous areas of the prostate, focal therapy should be considered an investigational modality only. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the prostate contours drawn by two radiation oncologists and one radiologist on magnetic resonance (MR) and transrectal ultrasound (TRUS) images. TRUS intra- and inter-fraction variability as well as TRUS vs. MR inter-modality and inter-operator variability were studied. Material and methods: Thirty patients affected by localized prostate cancer and treated with interstitial high-doserate (HDR) prostate brachytherapy at the National Cancer Institute in Milan were included in this study. Twenty-five patients received an exclusive two-fraction (14 Gy/fraction) treatment, while the other 5 received a single 14 Gy fraction as a boost after external beam radiotherapy. The prostate was contoured on TRUS images acquired before (virtual US) and after (real US) needle implant by two radiation oncologists, whereas on MR prostate was independently contoured by the same radiation oncologists (MR1, MR2) and by a dedicated radiologist (MR3). Absolute differences of prostate volumes (│ΔV│) and craniocaudal extents (│Δdz│) were evaluated. The Dice's coefficient (DC) was calculated to quantify spatial overlap between MR contours. Results: Significant difference was found between Vvirtual and Vlive (p < 0.001) for the first treatment fractions and between VMR1 and VMR2 (p = 0.043). Significant difference between cranio-caudal extents was found between dzvirtual and dzlive (p < 0.033) for the first treatment fractions, between dzvirtual of the first treatment fractions and dzMR1 (p < 0.001) and between dzMR1 and dzMR3 (p < 0.01). Oedema might be responsible for some of the changes in US volumes. Average DC values resulting from the comparison MR1 vs. MR2, MR1 vs. MR3 and MR2 vs. MR3 were 0.95 ± 0.04 (range, 0.82-0.99), 0.87 ± 0.04 (range, 0.73-0.91) and 0.87 ± 0.04 (range, 0.72-0.91), respectively. Conclusions: Our results demonstrate the importance of a multiprofessional approach to TRUS-guided HDR prostate brachytherapy. Specific training in MR and US prostate imaging is recommended for centers that are unfamiliar with HDR prostate brachytherapy. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have compared the implant quality of linked and loose seeds for prostate brachytherapy. This study aimed to evaluate and compare plan reproducibility of intraoperatively built custom linked seeds and loose seeds for prostate brachytherapy. Material and methods: Between December 2010 and March 2014, 76 localized prostate cancer patients received Iodine-125 brachytherapy with external beam radiotherapy. Linked and loose seeds were implanted in 39 and 37 patients, respectively. The primary endpoint was the mean (± standard deviation) of the absolute change in the minimum dose received by 90% of the prostate volume between intraoperative and post-operative planning (ΔD90) to confirm plan reproducibility. Comparisons between the groups were evaluated using 2-sample t tests. Results: The ΔD90 values were 6.95 ± 11.6% and -0.41 ± 8.5% for the loose and linked seed groups, respectively (p < 0.01). The linked seed group showed decreased post-operative D90 (118.8% vs. 127.2%), V150 (51.7% vs. 66.7%), and RV100 (0.44 ml vs. 0.61 ml) compared to the loose seed group (p < 0.01), whereas lung migration tended to be reduced (0% vs. 8%). Conclusions: The plan reproducibility of the linked seed group was better than that of the loose seed group. Moreover, the linked seed group showed less migration and lower rectal dose. [ABSTRACT FROM AUTHOR]