The use of hormonal therapy with radiotherapy for prostate cancer: analysis of prospective randomised trials.
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ABSTRACT:
SUBMITTER: Gottschalk AR
PROVIDER: S-EPMC2409615 | biostudies-other | 2004 Mar
REPOSITORIES: biostudies-other
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Project description:Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with nonmetastatic advanced prostate cancer, as well as frankly metastatic disease. Today's standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g., leuprolide), second-generation nonsteroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today's standard of care will require an accounting of an individual's androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.
| S-EPMC8152444 | biostudies-literature
Project description:BackgroundObservational studies suggest that hormonal contraceptive use may increase depressive symptoms in women, but it is unclear whether the effect is causal.AimsTo quantitatively examine the evidence from randomised clinical trials for the link between hormonal contraceptive use and depressive symptoms.MethodWe performed a systematic review and network meta-analysis of randomised clinical trials comparing women randomised to any form of a hormonal contraceptive with women randomised to any other form of a (non-)hormonal contraceptive or placebo. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, PsycINFO, EMCare and EMBASE, from inception to 1 May 2020. Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. A random-effect Bayesian network meta-analysis was conducted, with change in depressive symptoms between baseline and three cycles as outcome.ResultsThis review identified 3492 records, of which 14 trials were eligible and 12 could be included in the network meta-analysis. These trials included 5833 participants (mean age per study range: 16.8-32.4 years) and compared 10 different interventions. Compared with placebo, hormonal contraceptive use did not cause worsening of depressive symptoms (standardised mean difference: median, -0.04; range, -0.17 [95% credible interval -0.46 to 0.13] to 0.13 [95% credible interval -0.28 to 0.56]).ConclusionsThis study suggests that hormonal contraceptive use does not lead to an increase in depressive symptoms in adult women. Future studies should include first-time users, to confirm the results in young women.
| S-EPMC8220855 | biostudies-literature
Project description:Background: Despite the increasing worldwide utilization of stereotactic body radiation therapy (SBRT) for prostate cancer, there are no known summative data regarding its safety and efficacy. To address this knowledge gap, we conducted a PRISMA-guided systematic review and meta-analysis of prospective prostate SBRT trials. Results: Fourteen trials with a total of 2,038 patients were included. Median follow-up was 37 months (range 6-55 months). Most patients had cT1-T2a, Gleason ?7 disease with median pre-treatment PSAs of 5-10; 1,042 (51%) were low-risk, 744 (37%) were intermediate-risk, 158 (8%) were high-risk, and the remainder were unreported. Doses ranged from 33.5-50.0 Gy, most typically in 5 fractions, with nearly all studies delivering nondaily fractionation with some type of daily image guidance. Outcomes were converted into counts at the end of one year. The pooled rate of FFBF was 98% [95% confidence interval, 97-98%]. The pooled rate of late grade ?3 gastrointestinal and genitourinary toxicities were 1% [0-5%] and 2% [1-3%], respectively. Methods: PubMed and Google Scholar were queried for prospective studies evaluating survival and/or toxicity outcomes in SBRT (?5 fractions) for localized prostate cancer. Pooled rates of freedom from biochemical failure (FFBF) and late grades ?3 gastrointestinal (GI) and genitourinary (GU) toxicities were assessed. Meta-analysis of proportions was logit transformed and pooled using generalized linear mixed models (both fixed and random effects) and subsequently back transformed to standard proportions. Conclusions: Despite the lack of long-term follow-up and heterogeneity of the available evidence, prostate SBRT affords appropriate biochemical control with few high-grade toxicities. These data have implications for ongoing worldwide utilization of prostate SBRT as well as ongoing prospective investigations.
| S-EPMC6771455 | biostudies-literature
Project description:BackgroundThe 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.MethodsThe 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.FindingsBetween 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.InterpretationIn 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.FundingNational Cancer Institute.
| S-EPMC6540797 | biostudies-literature
Project description:IntroductionThe systemic therapy, especially androgen deprivation therapy (ADT), is currently recommended for patients with oligometastatic prostate cancer (PCa). However, the results have not been satisfactory including adverse reactions and castration resistance. Therefore, it is necessary to explore more effective treatment to prolong biochemical progression-free survival (bPFS) and delay the start of hormonal therapy for treating oligometastatic PCa. Stereotactic body radiotherapy (SBRT) is an emerging treatment alternative for patients with oligometastases with high local control rates and minimal toxic effects. This prospective trial aims to demonstrate whether SBRT for the oligometastases of hormone-sensitive PCa can delay the start of ADT and prolong the time from inception of the study to castration-resistant prostate cancer (CRPC).Methods and analysisPatients with ≤3 oligometastatic recurrences, diagnosed on Ga-68 prostate-specific membrane antigen PET/CT, will be randomised in a 1:1 ratio between arm A (ADT only) and arm B (SBRT for oligometastases only). SBRT is conducted by CyberKnife with prescription dose 30-50 Gy in 3-5 fractions. One of the primary endpoints is ADT-free survival of arm B, the other is the time from inception of the study to CRPC. The secondary endpoints include radiotherapy-related toxicity, ADT-related toxicity, bPFS, local PFS and overall survival. Toxicity will be assessed using the National Cancer Institute Common Toxicity Criteria V.5.0.Ethics and disseminationThis protocol was approved by the institutional review board of Shanghai Changhai Hospital (CHEC2020-101). This is a randomised control clinical trial comparing SBRT to ADT for men with oligometastatic PCa. The study will be performed in compliance with applicable local legislation and in accordance with the ethical principles developed by the World Medical Association in the Declaration of Helsinki 2013. Study results will be disseminated through conferences and peer-reviewed scientific journals.Trial registration numberClinicaltrials.gov identifier:NCT04599686.
| S-EPMC9528669 | biostudies-literature
Project description:The aim of this research was to identify miRNAs that are associated with neoadjuvant hormonal therapy resisitance in prostate cancer.
2022-11-01 | GSE186994 | GEO
Project description:In patients with prostate cancer, earlier use and longer duration of new-generation hormonal therapy (NGHT), added to androgen deprivation therapy, requires careful evaluation of cognitive function. The aim of this systematic review is to describe the evidence about cognitive function in all the randomized trials (RCTs) testing NGHT (abiraterone, enzalutamide, apalutamide, darolutamide). We assessed the availability of both investigator-assessed cognitive impairment and disorders and patient-reported evaluation of cognitive function. Nineteen RCTs (17,617 patients) were included. The investigator-based evaluation of cognitive impairment was available in seven RCTs (36.8%). In total, 19/19 RCTs (100%) included patient-reported outcomes (PROs) collection, but PRO tools adopted allowed evaluation of cognitive function in two RCTs (10.5%). Among them, PRO-based cognitive function results were presented only in one RCT (5.3%): in ENZAMET, mean changes from baseline were worse with enzalutamide than with placebo, but deterioration-free survival favored enzalutamide. Despite cognitive deterioration could be relevant, clinical development of NGHT has not included a systematic evaluation of cognitive function. Assessment by investigators is at risk of underreporting, and commonly used PROs do not allow proper cognitive function analysis. Furthermore, the methodology of analysis can jeopardize the interpretation of results. Although direct comparisons are scanty, there could be differences between different NGHTs.
| S-EPMC7564823 | biostudies-literature
Project description:BackgroundThis study assesses the use of hormonal therapy to treat high-risk localized prostate cancer (HRLPCa) cases diagnosed between 2005 and 2015.MethodsAll N0-XM0 with ≥T3a, or PCa cases with poorly differentiated feature (equivalent to Gleason score ≥ 8), diagnosed between 2005 and 2015 were extracted from German population-based cancer registries. Cases treated by surgery or chemotherapy were excluded. Description of hormonal therapy use by HRLPCa cases' profile was presented. Relative risk (RR) was computed with a log-link function to identify factors associated with hormonal therapy use among radiotherapy-treated HRLPCa cases.ResultsA total of 5361 HRLPCa cases were analyzed. Only 27.6% (95% confidence interval [CI]: 26.4-28.8%) of the HRLPCa cases received hormonal therapy in combination with radiotherapy. The use of combined hormonal therapy and radiotherapy varied from 19.8% in Saxony to 47.8% in Schleswig-Holstein. Application of hormonal therapy was higher for the locally advanced cases compared to the poorly differentiated cases (relative risk [RR] = 1.28; 95%CI: 1.19, 1.37). Older patients showed a slightly increased use of hormonal therapy (RR for a 10-year age increase = 1.09; 95%CI: 1.02, 1.16). Compared to PCa cases from the most affluent residential areas, cases from the least affluent (RR = 0.71; 95%CI: 0.55, 0.92) and medium (RR = 0.75; 95%CI: 0.58, 0.96) areas had decreased use of hormonal therapy. The introduction of the German S3-guideline did not make a marked difference in the uptake of both hormonal therapy and radiotherapy (RR = 1.02; 95%CI: 0.95, 1.09).ConclusionThis study found a low use of hormonal therapy among HRLPCa patients treated without surgery. The introduction of the German S3-guideline for prostate cancer treatment does not seem to have impacted hormonal therapy use.
| S-EPMC9171996 | biostudies-literature
Project description:PurposeThe sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).Materials and methodsIndividual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.ResultsOverall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.ConclusionADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.
| S-EPMC9902004 | biostudies-literature
Project description:ImportanceTechnical advances in treatment of prostate cancer and a better understanding of prostate cancer biology have allowed for hypofractionated treatment courses using a higher dose per fraction. Use of ultrahypofractionated stereotactic body radiotherapy (SBRT) has also been characterized.ObjectiveTo characterize US national trends of different RT fractionation schemes across risk groups of prostate cancer.Design, setting, and participantsThis retrospective cohort study used data collected by the National Cancer Database (NCDB) to characterize the fractionation regimens used for 302 035 patients diagnosed as having prostate cancer from January 1, 2004, to December 31, 2020, who underwent definitive RT. The analysis was performed between February 1 and April 30, 2023.ExposureStereotactic body RT or ultrahypofractionation, defined as 5 or fewer fractions of external beam RT (EBRT), moderate hypofractionation, defined as 20 to 28 fractions of EBRT, or conventional fractionation, defined as all remaining EBRT fractionation schemes.Main outcomes and measuresTemporal trends and clinical and sociodemographic factors associated with SBRT, moderate hypofractionation, and conventional fractionation use.ResultsA total of 302 035 men receiving EBRT for localized prostate cancer between 2004 and 2020 were identified (40.1% aged 60-69 years). Black patients comprised 17.6% of this cohort; White patients, 77.9%; and other races and ethnicities, 4.5%. Patients with low-risk disease comprised 17.5% of the cohort; favorable intermediate-risk disease, 23.5%; unfavorable intermediate-risk disease, 23.9%; and high-risk disease, 35.1%. Treatment consisted of conventional fractionation for 81.2%, moderate hypofractionation for 12.9%, and SBRT for 6.0%. The rate of increase over time in patients receiving SBRT compared with conventional fractionation was higher (adjusted odds ratio [AOR] for 2005 vs 2004, 3.18 [95% CI, 2.04-4.94; P < .001]; AOR for 2020 vs 2004, 264.69 [95% CI, 179.33-390.68; P < .001]) than the rate of increase in patients receiving moderate hypofractionation compared with conventional fractionation (AOR for 2005 vs 2004, 1.05 [95% CI, 0.98-1.12; P = .19]; AOR for 2020 vs 2004, 4.41 [95% CI, 4.15-4.69; P < .001]). Compared with White patients, Black patients were less likely to receive SBRT compared with conventional fractionation or moderate hypofractionation (AOR for conventional fractionation, 0.84 [95% CI, 0.80-0.89; P < .001]; AOR for moderate hypofractionation, 0.77 [95% CI, 0.72-0.81; P < .001]). Compared with 2019, patients treated with all fractionation regimens declined in 2020 by 24.4%.Conclusions and relevanceIn this hospital-based cohort study of patients with prostate cancer treated with definitive EBRT, use of moderate hypofractionation and SBRT regimens for definitive prostate cancer treatment has increased from 2004 to 2020. Despite this increasing trend, findings suggest potential health care disparities for Black patients receiving EBRT for localized prostate cancer. The number of patients treated with EBRT in the year 2020 decreased, coinciding with official onset of the COVID-19 pandemic in March 2020.
| S-EPMC10565603 | biostudies-literature