Radiotherapy For Localized Prostate Cancer Research Articles

External beam radiotherapy and radical prostatectomy are associated with better survival in Asian prostate cancer patients.

To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients. In the Surveillance, Epidemiology and End Results database 2004-2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics. Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2). Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.

Hybrid Tomo-Helical and Tomo-Direct radiotherapy for localized prostate cancer.

PurposeThe aim of the study is to present a new planning approach to provide better planning target volume (PTV) coverage and reduce bladder and rectum dose with hybrid Tomo‐Helical (TH)/Tomo‐Direct (TD) radiotherapy (RT) for localized prostate cancer (LPC).MethodsTwenty‐five LPC patients were included in this retrospective study. TH plans, TD plans, and hybrid TH/TD plans were created. Lateral beams were used for the hybrid TD plan and the prescribed dose was 70 Gy in 28 fractions (hybrid plans were combined 45 Gy/ 18 fxs for TH and 25 Gy/10 fxs for TD). Doses of PTV (D2%, D98%, D50%, homogeneity index (HI), conformity index (CI), coverage) and organs at risk (OARs) (V50%, V35%, V25%, V5%, and V95%) were analyzed. The Wilcoxon signed‐rank test was used to analyze the difference in dosimetric parameters. p‐Value < 0.05 was considered statistically significant.ResultsTH plans showed better CI, and target coverage (p < 0.01) than TD and hybrid plans in all patient plan evaluations. However, TD plans D2%, D98%, and D50% doses were better than TH and hybrid plans. The HI values were similar between the three plans. Significant reductions in bladder and rectum V50%, V35%, and V25% doses (p < 0.001) were observed with hybrid plans compared to TH and TD. Penile bulb V95% and bowel V5% doses were better in the hybrid plans. Left and right femoral head V5% doses were higher in the hybrid plan compared to others (p < 0.001).ConclusionConcurrently hybrid TH/TD RT plan can be a good option to reduce the doses of the rectum and bladder in the RT of LPC.

EDITORIAL COMMENT

In this interesting study, an automatically calculated electronic comorbidity measure, the Care Assessment Needs (CAN) score, was studied as predictor of life expectancy in a huge Veterans Health Administration (VHA) patient sample. 1 N. N. et al. Using an automated electronic health record score to estimate life expectancy in men diagnosed with prostate cancer in the Veterans Health Administration. Urology. 2021; ([in press]) Google Scholar The score was originally designed to estimate short-term risks of hospitalization and mortality. The authors demonstrated a strong association of the CAN score with medium-term mortality after prostate cancer diagnosis. 1 N. N. et al. Using an automated electronic health record score to estimate life expectancy in men diagnosed with prostate cancer in the Veterans Health Administration. Urology. 2021; ([in press]) Google Scholar Although this instrument may be automatically available in VHA patients, its high complexity may hinder its routine use in different institutions. Instruments predicting life expectancy to support treatment selection in men with early prostate cancer should not only be accurate but also simple to use. 2 Daskivich TJ Kwan L Dash A et al. Weighted versus unweighted Charlson score to predict long-term other-cause mortality in men with early-stage prostate cancer. Eur Urol. 2014; 66: 1002-1009 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar In contrast to some contrary claims, 3 Walz J Gallina A Perrotte P et al. Clinicians are poor raters of life-expectancy before radical prostatectomy or definitive radiotherapy for localized prostate cancer. BJU Int. 2007; 100: 1254-1258 Crossref PubMed Scopus (113) Google Scholar at least in candidates for radical prostatectomy, clinicians are probably able raters of life expectancy. In our radical prostatectomy series, even patients with the highest risk of competing mortality (age-adjusted Charlson score of 6 or higher, comprising only 4% of the sample) had a 10-year non-prostate cancer mortality rate of only 40% 4 Froehner M. Patient reported vs claims based measures of health for modeling life expectancy in men with prostate cancer. Letter. J Urol. 2021; 205: 1235-1236 Crossref Scopus (1) Google Scholar and the 50% level was not reached before narrowly 14 years. Complex tools requiring comprehensive data collection will probably not change routine decision making in candidates for radical prostatectomy regardless of their accuracy. If the risk classifications were, however, automatically calculated and readily available, there may be a different situation. Because of the huge sample size and the detailed information collected, the impressive data source used in this study 1 N. N. et al. Using an automated electronic health record score to estimate life expectancy in men diagnosed with prostate cancer in the Veterans Health Administration. Urology. 2021; ([in press]) Google Scholar should encourage further studies, for instance predicting 90-day mortality in vulnerable candidates for radical cystectomy.

PD08-09 META-ANALYSIS OF RADIATION THERAPY AND ANDROGEN DEPRIVATION THERAPY IN LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (PD08)1 Sep 2021PD08-09 META-ANALYSIS OF RADIATION THERAPY AND ANDROGEN DEPRIVATION THERAPY IN LOCALIZED PROSTATE CANCER Tommy Jiang, Daniela Markovic, Jay Patel, Jesus Juarez, Martin Ma, David Shabsovich, Nicholas Zaorsky, Nicholas Nickols, Robert Reiter, David Elashoff, Matthew Rettig, Daniel Spratt, and Amar Kishan Tommy JiangTommy Jiang More articles by this author , Daniela MarkovicDaniela Markovic More articles by this author , Jay PatelJay Patel More articles by this author , Jesus JuarezJesus Juarez More articles by this author , Martin MaMartin Ma More articles by this author , David ShabsovichDavid Shabsovich More articles by this author , Nicholas ZaorskyNicholas Zaorsky More articles by this author , Nicholas NickolsNicholas Nickols More articles by this author , Robert ReiterRobert Reiter More articles by this author , David ElashoffDavid Elashoff More articles by this author , Matthew RettigMatthew Rettig More articles by this author , Daniel SprattDaniel Spratt More articles by this author , and Amar KishanAmar Kishan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001976.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Dose escalation of radiation therapy (RT) and the addition or prolongation of androgen deprivation therapy (ADT) have been independently shown to improve long-term outcomes in randomized trials for localized prostate cancer (PCa). We sought to explore the relative benefits of RT dose intensification and concomitant ADT compared to each other as well as to the historical standard of low dose RT. METHODS: PubMed was searched for Phase III randomized, controlled trials using RT for localized PCa following PRISMA guidelines. Selected trial arms were categorized as low or high dose as well as with or without ADT (categorized as short or long-term). 74 Gy was used as the threshold for “high dose” and 8 months of ADT therapy was the threshold for long-term ADT (LTADT). Outcomes included 5-year overall survival (OS), 5-year prostate cancer specific mortality (PCSM), and 5-year incidence of distant metastases (DM). Pairwise comparisons between treatments were performed using random effects meta regression models with a Bonferroni correction, where the null hypothesis was rejected for p <0.006 with respect to OS and PCSM (9 pairwise comparisons for each) and p <0.008 with respect to DM (6 pairwise comparisons). RESULTS: Forty trials recruiting a total of 21,429 patients met our inclusion criteria. Comparisons of each treatment type are shown in Table 1. Of note, when using low dose RT as the reference, low Dose RT + LTADT showed statistical improvement in PCSM (OR: 0.34 [0.22-0.54]), and DM (OR: 0.35 [0.20-0.63]). Dose escalation alone showed no statistical improvement in any reported outcome compared to low dose RT alone. When compared together, low Dose RT + LTADT was associated with improved 5-yr PCSM (OR: 0.40 [0.25-0.64]) when compared to high Dose RT alone. Improvement in OS and DM did not reach statistical significance. Overall, there was no statistical improvement in 5-year OS comparing any of the treatment modalities. CONCLUSIONS: The results of this meta-analysis suggest the benefit of adding any ADT (STADT or LTADT) to low dose RT alone outweighs the benefits of solely intensifying radiation dose. Dose escalation alone did not demonstrate any significant improvement in OS, PCSM, or DM and appeared to be associated with worse outcomes when compared to low dose RT + LTADT. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e117-e117 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tommy Jiang More articles by this author Daniela Markovic More articles by this author Jay Patel More articles by this author Jesus Juarez More articles by this author Martin Ma More articles by this author David Shabsovich More articles by this author Nicholas Zaorsky More articles by this author Nicholas Nickols More articles by this author Robert Reiter More articles by this author David Elashoff More articles by this author Matthew Rettig More articles by this author Daniel Spratt More articles by this author Amar Kishan More articles by this author Expand All Advertisement Loading ...

Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

BackgroundWhile multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer.MethodsUsing preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial.ResultsDose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001).ConclusionWhile limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

SP-0699 Radiotherapy for localised prostate cancer - How many modalities do we need? (30 mins)

SP-0699 Radiotherapy for localised prostate cancer - How many modalities do we need? (30 mins)

Impact of hydrogel peri-rectal spacer insertion on seminal vesicles intrafraction motion during 1.5 T-MRI-guided adaptive stereotactic body radiotherapy for localized prostate cancer.

MR-guided daily-adaptive radiotherapy is improving the accuracy in the planning and delivery phases of the treatment. Rectal hydrogel-spacer may help in mitigating organ motion, but few data are currently available. We aimed to assess any potential impact of the device on seminal vesicles motion by measuring translational and rotational shifts between the pre- and post-treatment MRI scans of a total of 50 fractions in the first 10 patients who underwent MR-guided prostate SBRT (35 Gy/5 fx). Of them, five patients received the hydrogel-spacer. The comparative analysis was performed using the Mann-Whitney U-test. Median rotational shifts were: in anteroposterior 0° (range, 0.097°/0.112°; SD = 0.05°) vs 0° (-0.162/0.04°; SD = 0.07°) in the no-spacer subgroup (p = 0.36); lateral shifts were 0° (-0.1°/0.54°; SD = 0.28°) vs -0.85° in the no-spacer cohort (-1.56°/0.124°; SD = 0.054°; p = 0.22). Cranio-caudal shifts were 0° (-0.121°/0.029°; SD = 0.06°) in the spacer-cohort vs 0° (-0.066°/0.087°; SD = 0.69°; p = 0.53). Median translational shifts were: in anteroposterior 0.9 mm (-0.014 mm/0.031 mm; SD = 0.036 mm) in the spacer-group vs 0.030 mm (-0.14 mm/0.03 mm; SD = 0.032 mm; p = 0.8); latero-lateral shifts were -0.042 mm (-0.047 mm/0.07 mm; SD = 0.054 mm), vs -0.023 mm (-0.027 mm/-0.01 mm; SD = 0.023 mm) in the no-spacer group (p = 0.94). In cranio-caudal, statistically significant shifts were reported: 0.082 mm (0.06 mm/0.15 mm; SD = 0.04 mm) vs 0.06 mm (-0.06/0.08 mm; SD = 0.09 mm) in the no-spacer cohort (p = 0.031). A favorable impact of the hydrogel-spacer on seminal vesicles motion was observed only in cranio-caudal translational shifts, although being not clinically significant. Further studies are required to fully investigate the potential contribution of this device on vesicles motion. MR-guided daily adaptive radiotherapy may represent a game changer for prostate stereotactic body radiotherapy, given the possibility to better visualize soft-tissues anatomy and to daily recalculate the treatment plan based on real-time conditions. The use of devices like rectal ballon or rectal gel spacers has gained interest in the last years for the possibility to better spare the rectum during prostate radiotherapy. This is one of the first experiences exploring the role of rectal spacer on seminal vesicles intrafraction motion during MR-guided SBRT for prostate cancer.

Radiotherapy planning parameters correlate with changes in the peripheral immune status of patients undergoing curative radiotherapy for localized prostate cancer

PurposeThe influence of radiotherapy on patient immune cell subsets has been established by several groups. Following a previously published analysis of immune changes during and after curative radiotherapy for prostate cancer, this analysis focused on describing correlations of changes of immune cell subsets with radiation treatment parameters.Patients and methodsFor 13 patients treated in a prospective trial with radiotherapy to the prostate region (primary analysis) and five patients treated with radiotherapy to prostate and pelvic nodal regions (exploratory analysis), already published immune monitoring data were correlated with clinical data as well as radiation planning parameters such as clinical target volume (CTV) and volumes receiving 20 Gy (V20) for newly contoured volumes of pelvic blood vessels and bone marrow.ResultsMost significant changes among immune cell subsets were observed at the end of radiotherapy. In contrast, correlations of age and CD8+ subsets (effector and memory cells) were observed early during and 3 months after radiotherapy. Ratios of T cells and T cell proliferation compared to baseline correlated with CTV. Early changes in regulatory T cells (Treg cells) and CD8+ effector T cells correlated with V20 of blood vessels and bone volumes.ConclusionsPatient age as well as radiotherapy planning parameters correlated with immune changes during radiotherapy. Larger irradiated volumes seem to correlate with early suppression of anti-cancer immunity. For immune cell analysis during normofractionated radiotherapy and correlations with treatment planning parameters, different time points should be looked at in future projects.Trial registration number:NCT01376674, 20.06.2011

Clinical experience and cost evaluation of magnetic resonance imaging -only workflow in radiation therapy planning of prostate cancer.

In radiation therapy (RT), significant improvements have been made recently particularly in the practices of planning imaging. This study aimed to conduct a cost evaluation between magnetic resonance imaging (MRI) -only and combined computed tomography (CT) and MRI workflows. The time-driven activity-based costing (TDABC) model was used to conduct a cost evaluation between the two workflows in those steps, where cost differences were expected. Costs were divided into capital costs and operational costs. The former consisted of fixed, one-time expenses, e.g. the purchase of a scanner, whereas the latter were partially based on the amount of activity consumed i.e. time required for image acquisition, image registration and structure contouring. In a review over a period of 10years for 300 annual prostate cancer patients, the total cost of the workflow steps included in the study for an individual patient applying the MRI-only workflow was 903 € (100%), comprised of 537 € (59%) capital costs and 366 € (41%) operational costs. The corresponding total cost for an individual patient applying the CT+MRI workflow was 922 € (100%), comprised of 197 € (21%) capital costs and 726 € (79%) operational costs. In 10years for 3000 patients, a total saving of 58,544 € (2%) was achieved with the MRI-only workflow compared with the dual imaging workflow. MRI-only workflow is a feasible and economic way to perform clinical RT for localized prostate cancer, in particular for medium- and large-sized departments treating a sufficient number of patients.

Dose-volume histogram parameters and patient-reported EPIC-Bowel domain in prostate cancer proton therapy.

PurposeTo analyze rectal dose and changes in quality of life (QOL) measured with the Expanded Prostate and Cancer Index Composite (EPIC) bowel domain in patients being treated for prostate cancer with curative-intent proton beam therapy (PBT) within a large single-institution prospective registry.Materials and MethodsData was collected from 243 patients with localized prostate cancer treated with PBT from 2016 to 2018. The EPIC survey was administered at baseline, end-of-treatment, 3, 6, and 12 months, then annually. Dose-volume histogram (DVH) parameters for the rectum were computed, and rectal dose was analyzed using BED (α/β = 3), EQD2Gy, and total dose. Repeated measures mixed models were implemented to determine the effect of patient, clinical, and treatment factors (including DVH) on patient-reported bowel symptom burden (EPIC-Bowel).ResultsTreatment overall resulted in changes in EPIC-Bowel scores (baseline score = 93.7), most notably at end-of-treatment (90.6) and 12 months (89.7). However, they returned to baseline at 36 months (92.9). On multivariate modeling, rectal BED D25 (Gy) ≥23% was significantly associated with decline in QOL scores measuring bother (p < 0.01; 4.06 points different).ConclusionRectal doses, specifically BED D25 (Gy) ≥23%, are significantly associated with decline in bowel bother-related QOL in patients undergoing definitive radiotherapy for localized prostate cancer. This study demonstrates BED as an independent predictor of bowel QOL across dose fractionations of PBT.

Impact of radiotherapy for localized prostate cancer on bladder function as demonstrated on urodynamics study: A systematic review.

This study aimed to describe the effects of bladder function following radiotherapy for localized prostate cancer by performing a systematic review on studies reporting on urodynamic findings after radiotherapy. This systematic review was conducted in accordance with PRISMA guidelines. The review protocol was registered at PROSPERO (CRD42021229037). A systematic search was conducted using PubMed, Cochrane Library, Scopus, and OVID Embase. Studies were included if they involved men who underwent urodynamic studies following radiotherapy for localized prostate cancer. A total of 798 articles were screened and five articles included. A qualitative analysis was performed. Bladder compliance appears to be impaired following radiotherapy, especially with longer followup. Impaired bladder compliance was reported in 18.8-62.5% of patients following radiotherapy. Bladder capacity was found to be statistically significantly lower following radiotherapy compared to pre-radiotherapy, and when compared with patients who did not undergo pelvic radiotherapy. Bladder outlet obstruction (BOO) persists post-radiotherapy in most patients at three and 18 months post-radiotherapy. De novo detrusor overactivity (DO) of 13.3% has been reported at 18 months post-radiotherapy. This review is limited by the absence of level I/II studies. Radiotherapy for localized prostate cancer results in decreased bladder compliance and capacity demonstrated on urodynamic studies. Resolution of BOO appears less likely in comparison to series on radical prostatectomy. De novo DO may develop following radiotherapy, especially with longer followup. With only low level of evidence studies available at present, further high-quality, prospective studies are important to elucidate the impact of radiotherapy on bladder and urethral function.

Late Gastrointestinal Tolerance After Prostate Radiotherapy: Is the Anal Canal the Culprit? A Narrative Critical Review.

IntroductionLate gastro-intestinal toxicities (LGIT) secondary to pelvic radiotherapy (RT) are well described in the literature. LGIT are mainly related to rectal or ano-rectal irradiation; however, involvement of the anal canal (AC) in the occurrence of LGIT remains poorly described and understood.Materials and MethodsThe aim of this work was to explore the potential role of the AC in the development of LGIT after prostate irradiation and identify predictive factors that could be optimized in order to limit these toxicities. This narrative literature review was realized using the Pubmed database. We identified original articles published between June 1997 and July 2019, relating to LGIT after RT for localized prostate cancer and for which AC was identified independently. Articles defining the AC as part of an anorectal or rectal volume only were excluded.ResultsA history of abdominal surgery or cardio-vascular risk, anticoagulant or tobacco use, and the occurrence of acute GIT during RT increases the risk of LGIT. A dose-effect relationship was identified between dose to the AC and development of LGIT. Identification and contouring of the AC and adjacent anatomical structures (muscles or nerves) are justified to apply specific dose constraints. As a limitation, our review mainly considered on 3DCRT which is no longer the standard of care nowadays; we did not identify any reports in the literature using moderately hypofractionated RT for the prostate and AC specific dosimetry.ConclusionThese results suggest that the AC may have an important role in the development of LGIT after pelvic RT for prostate cancer. The individualization of the AC during planning should be recommended in prospective studies.

Early health economic analysis of 1.5 T MRI-guided radiotherapy for localized prostate cancer: Decision analytic modelling

Background and purpose1.5 Tesla magnetic resonance imaging radiotherapy linear accelerator (MR-Linac) is gaining interest for treatment of localized prostate cancer. Clinical evidence is lacking and it therefore remains uncertain whether MR-Linac is cost-effective. An early health economic analysis was performed to calculate the necessary relative reduction in complications and the maximum price of MR-Linac (5 fractions) to be cost-effective compared to 5, 20 and 39 fractionation schedules of external beam radiotherapy (EBRT) and low-dose-rate (LDR) brachytherapy. Materials and methodsA state transition model was developed for men with localized prostate cancer. Complication rates such as grade ≥2 urinary, grade ≥2 bowel and sexual complications, and utilities were based on systematic literature searches. Costs were estimated from a Dutch healthcare perspective. Threshold analyses were performed to identify the thresholds of complications and costs for MR-Linac to be cost-effective, while holding other outcomes such as biochemical progression and mortality constant. One-way sensitivity analyses were performed to outline uncertainty outcomes. ResultsAt €6460 per patient, no reductions in complications were needed to consider MR-Linac cost-effective compared to EBRT 20 and 39 fractions. Compared to EBRT 5 fractions and LDR brachytherapy, MR-Linac was found to be cost-effective when complications are relatively reduced by 54% and 66% respectively. Results are highly sensitive to the utilities of urinary, bowel and sexual complications and the probability of biochemical progression. ConclusionsMR-Linac is found to be cost-effective compared to 20 and 39 fractions EBRT at baseline. For MR-Linac to become cost-effective over 5 fractions EBRT and LDR brachytherapy, it has to reduce complications substantially or be offered at lower costs.

Prognostic value of testosterone castration levels following androgen deprivation and high-dose radiotherapy in localized prostate cancer: Results from a phase III trial

Background/objectiveThe optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT). Patients and methodsThe DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum <20 ng/dL; median 20–49 ng/dL; and maximum ≥50 ng/dL. Kaplan–Meyer and Cox regression analysis were used for overall survival (OS) and Fine & Gray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery. ResultsThere were no statistically significant differences in 10-year bDFS, MFS, or OS between the <20 ng/mL and 20–49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28–33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups. ConclusionsOur results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20–49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Announcing the Lancet Commission on Prostate Cancer

Prostate cancer is the second most frequent cancer in men, and there were about 1·4 million new cases around the world in 2020. 1 Sung H Ferlay J Siegel RL et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; (published online Feb 4.)https://doi.org/10.3322/caac.21660 Crossref PubMed Scopus (2010) Google Scholar , 2 Ferlay J Ervik M Lam F et al. Global Cancer Observatory: cancer today. https://gco.iarc.fr/todayDate: 2020 Date accessed: April 16, 2021 Google Scholar Prostate cancer accounts for an estimated 15% of all cancer cases in men worldwide and is the most common form of cancer in men in in 112 countries (figure). Globally, there are many hundreds of thousands of premature deaths from prostate cancer annually, 3 Bray F Ferlay J Soerjomataram I Siegel RL Torre LA Jemal A Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394-424 Crossref PubMed Scopus (33702) Google Scholar and a huge toll in morbidity, particularly bone metastases leading to pain, fracture, and disability. 4 James N Pirrie S Pope A et al. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer. Health Technol Assess. 2016; 20: 1-288 Crossref PubMed Scopus (19) Google Scholar Curative treatment itself can also cause adverse effects on urinary and sexual function. 5 Hamdy FC Donovan JL Lane JA et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016; 375: 1415-1424 Crossref PubMed Scopus (1360) Google Scholar There is a growing tension between the need to diagnose advanced disease early while not overdiagnosing lower risk disease that probably does not need treatment.

Ultrahypofractionated radiotherapy for localized prostate cancer with simultaneous boost to the dominant intraprostatic lesion: a plan comparison

To compare different stereotactic body techniques-intensity-modulated radiotherapy with photons and protons, applied to radiotherapy of prostatic cancer-with simultaneous integrated boost (SIB) on the dominant intraprostatic lesion (DIL). Ten patients were selected for this planning study. Dosimetric results were compared between volumetric modulated arc therapy, intensity-modulated radiation therapy (IMRT), and intensity-modulated proton therapy both with two (IMPT 2F) and five fields (IMPT 5F) planning while applying the prescription schemes of 7.25 Gy/fraction to the prostate gland and 7.5 Gy/fraction to the DIL in 5 fractions. Comparison of the coverages of the planning target volumes showed that small differences exist. The IMPT-2F-5F techniques allowed higher doses in the targets; conformal indexes resulted similar; homogeneity was better in the photon techniques (2%-5%). Regarding the organs at risk, all the techniques were able to maintain the dose well below the prescribed constraints: in the rectum, the IMPT-2F-5F and IMRT were more efficient in lowering the intermediate doses; in the bladder, the median dose was significantly better in the case of IMPT (2F-5F). In the urethra, the best sparing was achieved only by IMPT-5F. Stereotactic radiotherapy with SIB for localized prostate cancer is feasible with all the investigated techniques. Concerning IMPT, the two-beam technique does not seem to have a greater advantage compared to the standard techniques; the 5-beam technique seems more promising also accounting for the range uncertainty.

Safety of image-guided radiotherapy in definitive radiotherapy for localized prostate cancer: a population-based analysis.

Objectives:Image-guided radiotherapy (IGRT) is a recommended advanced radiation technique that is associated with fewer acute and chronic toxicities. However, one Phase III trial showed worse overall survival in the IGRT arm. The purpose of this observational study is to evaluate the impact of IGRT on overall survival.Methods:We used the Taiwan Cancer Registry Database to enroll cT1-4N0M0 prostate cancer patients who received definitive radiotherapy between 2011 and 2015. We used inverse probability treatment weighting (IPW) to construct balanced IGRT and non-IGRT groups. We compared the overall survival of those in the IGRT and non-IGRT groups. Supplementary analyses (SA) were performed with alternative covariates in propensity score (PS) models and PS approaches. The incidence rates of prostate cancer mortality (IPCM), other cancer mortality (IOCM), and cardiovascular mortality (ICVM) were also evaluated.Results:There were 360 patients in the IGRT arm and 476 patients in the non-IGRT arm. The median follow-up time was 50 months. The 5-year overall survival was 88% in the IGRT arm and 86% in the non-IGRT arm (adjusted hazard ratio [HR] of death = 0.93; 95% CI, 0.61–1.45; p = 0.77). The SA also showed no significant differences in the overall survival between those in the IGRT and non-IGRT arms. Both groups did not significantly differ in terms of IPCM, IOCM, and ICVM.Conclusions:The overall survival of localized prostate cancer patients who underwent IGRT was not inferior to those who did not.Advances in knowledge:We demonstrated that the overall survival for prostate cancer patients with IGRT was not worse than those who did not undergo IGRT; this important outcome comparison has not been previously examined in the general population.

Multicentre International Study for the Prevention with iAluRil of Radio-induced Cystitis (MISTIC): A Randomised Controlled Study

BackgroundRadiation-induced cystitis is a common side effect of radiotherapy (RT) to the pelvic area. Hyaluronic acid (HA) and chondroitin sulfate (CS) are components of the urothelial mucosa and positive results have been obtained for intravesical HA/CS instillations for the treatment of urinary tract infections and bladder pain syndrome. HA/CS may also have a protective effect against RT bladder toxicity. ObjectiveTo investigate whether HA and CS protect the urothelium during RT, alleviate lower urinary tract symptoms, and improve quality of life. Design, setting, and participantsThis multicentre randomised controlled trial was conducted across seven centres in four countries. Male patients aged ≥18 yr scheduled to undergo primary intensity-modulated radiotherapy for localised prostate cancer were enrolled. InterventionPatients were randomised to intravesical HA/CS plus an oral formulation of curcumin, quercetin, HA, and CS (group A) or no treatment (group B). Outcome measurements and statistical analysisThe primary endpoint was absolute changes from baseline to follow-up in urinary domain scores for the Expanded Prostate Cancer Index Composite (EPIC), the International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ-MLUTS), and the EuroQol Group EQ-5D-5L questionnaire. Data analysis for efficacy and safety outcomes was performed using an intention-to-treat (ITT) approach; the ITT population was defined as all randomised patients. Results and limitationsOf 57 patients screened, 49 were enrolled and randomly assigned to either active treatment (group A, n = 25) or the control (group B, n = 24). Three patients in the control group withdrew after randomisation. Changes from baseline to 12 mo were worse in the control group for subtotal scores for urinary symptoms and impact of symptoms on quality of life and for the total score (p = 0.05, p = 0.003, and p = 0.008, respectively). There was a significant time × group interaction in favour of active treatment for the incontinence symptom score (p = 0.011) and bother score (p = 0.017). The absence of a sham procedure and/or placebo is the main limitation. ConclusionsOur results suggest that intravesical HA/CS in combination with an oral formulation may reduce urinary symptoms and improve QoL at short-term (1 yr) follow-up. Patient summaryWe investigated whether hyaluronic acid (HA) and chondroitin sulfate (CS) have a protective effect against the bladder toxicity of radiotherapy for prostate cancer. HA/CS used for weekly bladder irrigation for 6 wk and given orally with curcumin and quercetin for 12 wk reduced urinary incontinence symptoms and bother measured at 1-year follow-up. This may hold promise as a preventive treatment if the results are confirmed in further trials.

Inverse planning in high-dose rate brachytherapy improves quality of life of prostate cancer patients compared with forward planning.

To understand differences in quality of life outcomes between cases with forward planning and cases with inverse planning, we examine patients undergoing high-dose rate brachytherapy combined with external beam radiotherapy for localized prostate cancer. We prospectively identified 283 patients with localized prostate cancer and divided them into forward planning and inverse planning groups. We extracted data on doses to the prostate, rectum and urethra that could potentially affect quality of life. We also evaluated quality of life using the Japanese version of Medical Outcome Study 8-Items Short Form Health Survey and Expanded Prostate Cancer Index Composite at pre-treatment and at 3, 6, 12 and 24months after treatment. Wilcoxon signed rank test and Bonferroni correction were used to analyze the irradiation dose and any change in quality of life. Doses to the prostate and rectum were not significantly different between the two groups. Notably, however, doses to the urethra were significantly lower in the inverse planning group than in the forward planning group. Patients in the forward planning group had significantly poorer physical component summary scores at 3months according to survey results. In Expanded Prostate Cancer Index Composite, patients in the forward planning group had statistically significant poorer urinary, bowel and sexual scores than those in the inverse planning group. Quality of life related to decline in sexual function was significantly reduced in the inverse planning group. Inverse planning in high-dose rate brachytherapy could significantly improve quality of life of patients with prostate cancer.

Hypofractionated radiotherapy recommendations for localized prostate cancer in Brazil

SUMMARY OBJECTIVE: Several prospective randomized trials have shown that hypofractionation has the same efficacy and safety as the conventional fractionation in the treatment of localized prostate cancer. There are many benefits of hypofractionation, including a more convenient schedule for the patients and better use of resources, which is especially important in low- and middle-income countries like Brasil. Based on these data, the Brazilian Society of Radiotherapy (Sociedade Brasileira de Radioterapia) organized this consensus to guide and support the use of hypofractionated radiotherapy for localized prostate cancer in Brasil. METHODS: The relevant literature regarding moderate hypofractionation (mHypo) and ultra-hypofractionation (uHypo) was reviewed and discussed by a group of experts from public and private centers of different parts of Brasil. Several key questions concerning clinical indications, outcomes and technological requirements for hypofractionation were discussed and voted. For each question, consensus was reached if there was an agreement of at least 75% of the panel members. RESULTS: The recommendations are described in this article. CONCLUSION: This initiative will assist Brazilian radiation oncologists and medical physicists to safely treat localized prostate cancer patients with hypofractionation.