Should androgen deprivation therapy and other systemic treatments be used in men with prostate cancer and a rising PSA post-local treatments?
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ABSTRACT:
SUBMITTER: Patrikidou A
PROVIDER: S-EPMC8543684 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIntermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial.MethodsWe enrolled patients with a PSA level greater than 3 ng per milliliter more than 1 year after primary or salvage radiotherapy for localized prostate cancer. Intermittent treatment was provided in 8-month cycles, with nontreatment periods determined according to the PSA level. The primary end point was overall survival. Secondary end points included quality of life, time to castration-resistant disease, and duration of nontreatment intervals.ResultsOf 1386 enrolled patients, 690 were randomly assigned to intermittent therapy and 696 to continuous therapy. Median follow-up was 6.9 years. There were no significant between-group differences in adverse events. In the intermittent-therapy group, full testosterone recovery occurred in 35% of patients, and testosterone recovery to the trial-entry threshold occurred in 79%. Intermittent therapy provided potential benefits with respect to physical function, fatigue, urinary problems, hot flashes, libido, and erectile function. There were 268 deaths in the intermittent-therapy group and 256 in the continuous-therapy group. Median overall survival was 8.8 years in the intermittent-therapy group versus 9.1 years in the continuous-therapy group (hazard ratio for death, 1.02; 95% confidence interval, 0.86 to 1.21). The estimated 7-year cumulative rates of disease-related death were 18% and 15% in the two groups, respectively (P=0.24).ConclusionsIntermittent androgen deprivation was noninferior to continuous therapy with respect to overall survival. Some quality-of-life factors improved with intermittent therapy. (Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials.gov number, NCT00003653.).
| S-EPMC3521033 | biostudies-literature
Project description:BackgroundClinical trials in men with biochemically recurrent prostate cancer (BRPC) have been hampered by long survival times, making overall survival (OS) a difficult end point to reach. Intermediate end points are needed in order to conduct such trials within a more feasible time frame.Patients and methodsThis is a retrospective analysis of 450 men with BRPC following prostatectomy treated at a single institution between 1981 and 2010, of which 140 developed subsequent metastases. Androgen deprivation therapy (ADT) was deferred until after the development of metastases. Cox regression models were developed to investigate factors influencing OS.ResultsMedian metastasis-free survival (MFS) was 10.2 years [95% confidence interval (CI) 7.6-14.0 years]; median OS after metastasis was 6.6 years (95%CI 5.8-8.4 years). Multivariable Cox regressions identified four independently prognostic variables for OS: MFS (HR 0.77; 95% CI 0.63-0.94), number of metastases (≤3 versus ≥4; HR 0.50; 95% CI 0.29-0.85), pain (absent versus present; HR 0.43; 95% CI 0.25-0.72), and bisphosphonate use (yes versus no; HR 0.60; 95% CI 0.37-0.98).ConclusionsMFS emerged as an independent predictor of OS in men with BRPC treated with deferred ADT after the development of metastases. MFS may be a reasonable intermediate end point in future clinical trials. This observation requires prospective validation.
| S-EPMC3888237 | biostudies-literature
Project description:When a physician decides on a treatment and its schedule for a specific patient, information gained from prior patients and experience in the past is taken into account. A more objective way to make such treatment decisions based on actual data would be useful to the clinician. Although there are many mathematical models proposed for various diseases, so far there is no mathematical method that accomplishes optimization of the treatment schedule using the information gained from past patients or "rapid learning" technology. In an attempt to use this approach, we integrate the information gained from patients previously treated with intermittent androgen suppression (IAS) with that from a current patient by first fitting the time courses of clinical data observed from the previously treated patients, then constructing the prior information of the parameter values of the mathematical model, and finally, maximizing the posterior probability for the parameters of the current patient using the prior information. Although we used data from prostate cancer patients, the proposed method is general, and thus can be applied to other diseases once an appropriate mathematical model is established for that disease.
| S-EPMC4481271 | biostudies-literature
Project description:Androgen deprivation therapy (ADT) improves prostate cancer outcomes in specific clinical settings, but is associated with adverse effects, including cardiac complications and possibly thromboembolic complications. The objective of this study was to estimate the impact of ADT on thromboembolic events (TEs) in a population-based cohort.In the linked Surveillance, Epidemiology and End Results-Medicare database, we identified men older than 65 who were diagnosed with nonmetastatic prostate cancer between 1999 and 2005. Medical or surgical ADT was identified by Medicare claims for gonadotropin-releasing hormone agonists or bilateral orchiectomy at any time following diagnosis. TEs included deep venous thrombosis, pulmonary embolism, and arterial embolism. The impact of ADT on the risk of any TE and on total number of events was estimated, controlling for patient and tumor characteristics.Of 154,611 patients with prostate cancer, 58,466 (38%) received ADT. During a median follow-up of 52 months, 15,950 men had at least 1 TE, including 8829 (55%) who had ADT and 7121 (45%) with no ADT. ADT was associated with increased risk of a TE (adjusted hazard ratio = 1.56; 95% confidence interval, 1.50-1.61; P < .0001), and duration of ADT was associated with the total number of events (P < .0001).In this population-based cohort, ADT was associated with increased risk of a TE, and longer durations of ADT were associated with more TEs. Men with intermediate- and low-risk prostate cancer should be assessed for TE risk factors before starting ADT and counseled regarding the risks and benefits of this therapy.
| S-EPMC3678973 | biostudies-literature
Project description:Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer.In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures.At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups.Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.)
| S-EPMC3038121 | biostudies-literature
Project description:ContextDespite a lack of data, increasing numbers of patients are receiving primary androgen deprivation therapy (PADT) as an alternative to surgery, radiation, or conservative management for the treatment of localized prostate cancer.ObjectiveTo evaluate the association between PADT and survival in elderly men with localized prostate cancer.Design, setting, and patientsA population-based cohort study of 19,271 men aged 66 years or older receiving Medicare who did not receive definitive local therapy for clinical stage T1-T2 prostate cancer. These patients were diagnosed in 1992-2002 within predefined US geographical areas, with follow-up through December 31, 2006, for all-cause mortality and through December 31, 2004, for prostate cancer-specific mortality. Instrumental variable analysis was used to address potential biases associated with unmeasured confounding variables.Main outcome measuresProstate cancer-specific survival and overall survival.ResultsAmong patients with localized prostate cancer (median age, 77 years), 7867 (41%) received PADT, and 11,404 were treated with conservative management, not including PADT. During the follow-up period, there were 1560 prostate cancer deaths and 11,045 deaths from all causes. Primary androgen deprivation therapy was associated with lower 10-year prostate cancer-specific survival (80.1% vs 82.6%; hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.03-1.33) and no increase in 10-year overall survival (30.2% vs 30.3%; HR, 1.00; 95% CI, 0.96-1.05) compared with conservative management. However, in a prespecified subset analysis, PADT use in men with poorly differentiated cancer was associated with improved prostate cancer-specific survival (59.8% vs 54.3%; HR, 0.84; 95% CI, 0.70-1.00; P = .049) but not overall survival (17.3% vs 15.3%; HR, 0.92; 95% CI, 0.84-1.01).ConclusionPrimary androgen deprivation therapy is not associated with improved survival among the majority of elderly men with localized prostate cancer when compared with conservative management.
| S-EPMC2645653 | biostudies-literature
Project description:Pomegranate juice has been associated with PSA doubling time (PSADT) elongation in a single-arm phase II trial. This study assesses biological activity of two doses of pomegranate extract (POMx) in men with recurrent prostate cancer, using changes in PSADT as the primary outcome.This randomized, multi-center, double-blind phase II, dose-exploring trial randomized men with a rising PSA and without metastases to receive 1 or 3 g of POMx, stratified by baseline PSADT and Gleason score. Patients (104) were enrolled and treated for up to 18 months. The intent-to-treat (ITT) population was 96% white, with median age 74.5 years and median Gleason score 7. This study was designed to detect a 6-month on-study increase in PSADT from baseline in each arm.Overall, median PSADT in the ITT population lengthened from 11.9 months at baseline to 18.5 months after treatment (P < 0.001). PSADT lengthened in the low-dose group from 11.9 to 18.8 months and 12.2 to 17.5 months in the high-dose group, with no significant difference between dose groups (P = 0.554). PSADT increases >100% of baseline were observed in 43% of patients. Declining PSA levels were observed in 13 patients (13%). In all, 42% of patients discontinued treatment before meeting the protocol-definition of PSA progression, or 18 months, primarily due to a rising PSA. No significant changes occurred in testosterone. Although no clinically significant toxicities were seen, diarrhea was seen in 1.9% and 13.5% of patients in the 1- and 3-g dose groups, respectively.POMx treatment was associated with ? 6 month increases in PSADT in both treatment arms without adverse effects. The significance of this on-study slowing of PSADT remains unclear, reinforcing the need for placebo-controlled studies in this patient population.
| S-EPMC3549301 | biostudies-literature
Project description:Androgen deprivation therapy (ADT) has been an essential treatment option for treating prostate cancer (PCa). The role for hormonal treatment initially was restricted to men with metastatic and inoperable, locally advanced disease. Now it has been extended to neoadjuvant or adjuvant therapy for surgery and radiotherapy, for biochemical relapse after surgery or radiation, and even as primary therapy for non-metastatic disease. Fifty percent of PCa patients treated will receive ADT at some point. There is growing concern about the adverse effects and costs associated with more widespread ADT use. The adverse effects on quality of life (QoL), including physical, social and psychological well-being when men are androgen-deprived, may be considerable. This review examines the QoL issues in the following areas: body feminisation, sexual changes, relationship changes, cognitive and affective symptoms, fatigue, sleep disturbance, depression and physical effects. Further suggestions for therapeutic approaches to reduce these alterations are suggested.
| S-EPMC3735091 | biostudies-other
Project description:Androgen deprivation therapy (ADT) is a treatment used across the prostate cancer disease spectrum and works by suppressing testicular androgen production to castrate levels. Although ADT can provide survival benefits, it is also associated with increased risk for cardiovascular disease, metabolic syndrome, increased visceral fat mass, dyslipidemia, decreased arterial compliance, and diminished health-related quality of life. The Staying Strong And Healthy protocol is a telephone-delivered intervention led by a nurse coordinator to minimize the increased cardiovascular and metabolic risks associated with ADT. This study will evaluate the feasibility of the protocol and provides the foundation for future behavioral interventions across diverse populations of men on ADT.
| S-EPMC6767619 | biostudies-literature
Project description:ImportanceAndrogen-deprivation therapy (ADT) plus docetaxel is the standard of care in hormone-naive metastatic prostate cancer but is of uncertain benefit in a nonmetastatic, high-risk prostate cancer setting.ObjectiveTo assess the benefit of ADT plus docetaxel in patients presenting with rising prostate-specific antigen (PSA) levels after primary local therapy and high-risk factors but no evidence of metastatic disease.Design, setting, and participantsThis open-label, phase 3, randomized superiority trial comparing ADT plus docetaxel vs ADT alone enrolled patients from 28 centers in France between June 4, 2003, and September 25, 2007; final follow-up was conducted April 12, 2017, and analysis was performed May 2 to July 31, 2017. Patients had undergone primary local therapy for prostate cancer, were experiencing rising PSA levels, and were considered to be at high risk of metastatic disease. Stratification was by prior local therapy and PSA-level doubling time (≤6 vs >6 months), and intention-to-treat analysis was used.InterventionsPatients were randomly assigned to receive ADT (1 year) plus docetaxel, 70 mg/m2 (every 3 weeks [6 cycles]), or ADT alone (1 year).Main outcomes and measuresThe primary outcome was PSA progression-free survival (PSA-PFS). Secondary end points were PSA response, radiologic PFS, overall survival, safety, and quality of life.ResultsOverall, 254 patients were randomized (1:1) to the trial; median age, 64 years in the ADT plus docetaxel arm, 66 years in the ADT alone arm. At a median follow-up of 30.0 months, the median PSA-PFS was 20.3 (95% CI, 19.0-21.6) months in the ADT plus docetaxel arm vs 19.3 (95% CI, 18.2-20.8) months in the ADT alone arm (hazard ratio [HR], 0.85; 95% CI, 0.62-1.16; P = .31). At a median follow-up of 10.5 years, there was no significant between-arm difference in radiologic PFS (HR, 1.03; 95% CI, 0.74-1.43; P = .88). Overall survival data were not mature. The most common grade 3 or 4 hematologic toxic effects in the ADT plus docetaxel arm were neutropenia (60 of 125 patients [48.0%]), febrile neutropenia (10 [8.0%]), and thrombocytopenia (4 [3.0%]). There was no significant between-arm difference in overall quality of life.Conclusions and relevanceCompared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA-PFS in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease.Trial registrationFrench Health Products Safety Agency identifier: 030591; ClinicalTrials.gov identifier: NCT00764166.
| S-EPMC6512307 | biostudies-literature