scholarly journals Real World Evaluation of Upfront Docetaxel in Metastatic Castrate Sensitive Prostate Cancer

2021 ◽  
Author(s):  
Jenny Isaksson ◽  
Henrik Green ◽  
Dimitrios Papantoniou ◽  
Linn Pettersson ◽  
Mats Andén ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Real World ◽  
Treatment Strategy ◽  
Statistical Significance ◽  
Combined Treatment ◽  
Dose Intensity ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Study Cohort

Abstract Background: Recent randomised phase III trials demonstrate survival benefit for the addition of upfront docetaxel to androgen deprivation therapy (ADT) in metastatic castrate sensitive prostate cancer (mCSPC). Following its implementation in routine care, this combined treatment strategy needs further evaluation in a real world setting.Methods: A multicentre retrospective cohort study in the South East Health care region of Sweden was conducted. All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included. Primary endpoint was progression free survival (PFS) at 12 months and secondary endpoints were PFS at 24 months, overall survival (OS), treatment intensity, adverse events, and unplanned hospitalisations. Exploratory analyses on potentially prognostic parameters were performed.Results: 94 patients were eligible and formed the study cohort. PFS at 12 and 24 months were 75% (95% CI 66-84) and 58% (46-70). OS at 12 and 24 months were 93% (87-99) and 86% (76-96). 91% (n=86) initiated docetaxel according to the standard protocol of 75 mg/m2 every 3 weeks (6 cycles), whereas 9% (n=8) received a modified protocol of 50 mg/m2 every 2 weeks (9 cycles). The average overall dose intensity for those commencing standard treatment was 91%. Univariate cox regression analyses revealed that baseline PSA >180 vs <180 and presence vs absence of distant metastases were negative prognostic factors (HR 2.86, 95% CI 1.39-5.87, p =0.0041 and 3.36, 95% CI 1.03-10.96, p=0.045). Following multivariate analysis, the statistical significance remained for PSA (2.51, CI 1.21-5.19, p =0.013) but not for metastatic status (2.60, 95% CI 0.78-8.65, p=0.12). Febrile neutropenia was recorded in 21% (n=20) and 26% (n=24) had at least one episode of unplanned hospitalisation under and up to 30 days after the treatment course. Conclusions: The outcome and safety profile of upfront docetaxel in addition to androgen deprivation therapy in metastatic castrate sensitive prostate cancer appear similar in real world and randomised controlled populations. Further implementation of this treatment strategy is encouraged.

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

2021 ◽  
Author(s):  
Tommy Jiang ◽  
Daniela Markovic ◽  
Jay Patel ◽  
Jesus E. Juarez ◽  
Ting Martin Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Dose Escalation ◽  
Low Dose ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Treatment Intensification ◽  
Meta Regression

Abstract Background While 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. Methods Using 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. Results Dose-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). Conclusion While 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.

scholarly journals Effect of Salvage Radiotherapy and Endocrine Therapy on Patients with Biochemical Recurrence After Prostate Cancer Operation— a Meta‑Analysis

2021 ◽  
Vol 15 (3) ◽  
pp. 155798832110248
Author(s):  
Yong Yuan ◽  
Qiang Zhang ◽  
Chaofan Xie ◽  
Tao Wu
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Endocrine Therapy ◽  
Androgen Deprivation Therapy ◽  
Biochemical Recurrence ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Androgen Deprivation ◽  
Salvage Radiotherapy ◽  
End Point

Context: Several studies reported the application of androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. Objective: To perform a systematic review and meta-analysis evaluating of endocrine therapy and radiotherapy in patients with biochemical recurrence after prostate cancer surgery. The primary end point was biochemical progression-free survival (bPFS). Secondary end point was overall survival (OS). Methods: A systematic review of PubMed/Medline, Embase, and Cochrane databases to identify relevant studies published in English up to March 2020. Twelve studies were selected for inclusion. Results: There were 11 studies included in the present study. Including two randomized controlled trials and nine cohort studies. The meta-analysis shows a significant bPFS benefit from androgen deprivation therapy and radiotherapy in patients with biochemical recurrence after prostate cancer operation. (hazard ratio [HR]: 0.57; 95% confidence interval CI, 0.52–0.63; p < .001). For patients with GS < 7 and low-risk patients, combined treatment can have a benefit for BPFs (HR: 0.53; 95% CI, 0.37–0.76; HR: 0.58; 95% CI, 0.36–0.93). Androgen deprivation therapy and radiotherapy in patients with biochemical recurrence was associated with a slightly OS improvement (HR: 0.73; 95% CI, 0.57–0.93; p = 0.01). Conclusions: Compared with salvage radiotherapy alone, This meta-analysis shows a significant bPFS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence after prostate cancer operation. And benefit more for high-risk groups. However, there was no significant benefit in group GS ≥ 8. It shows a slightly OS benefit from endocrine therapy combined with salvage radiotherapy in patients with biochemical recurrence.

scholarly journals Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial

2020 ◽  
Vol 38 (6) ◽  
pp. 593-601 ◽  
Author(s):  
Shawn Malone ◽  
Soumyajit Roy ◽  
Libni Eapen ◽  
Choan E ◽  
Robert MacRae ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Definitive Treatment ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Grade 3

PURPOSE Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

scholarly journals Effect of Androgen Deprivation Therapy on Other-Cause of Mortality in Elderly Patients with Clinically Localized Prostate Cancer Treated with Modern Radiotherapy: Is There a Negative Impact?

2019 ◽  
Vol 8 (3) ◽  
pp. 338 ◽  
Author(s):  
Hideya Yamazaki ◽  
Koji Masui ◽  
Gen Suzuki ◽  
Satoaki Nakamura ◽  
Norihiro Aibe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Androgen Deprivation Therapy ◽  
Negative Impact ◽  
Statistical Significance ◽  
Intensity Modulated Radiotherapy ◽  
Risk Groups ◽  
Androgen Deprivation ◽  
Localized Prostate Cancer ◽  
High Dose

The influence of androgen deprivation therapy (ADT) on other-cause of mortality (OCM) was investigated in patients with localized prostate cancer treated with modern high-dose radiotherapy. A retrospective review was conducted on 1125 patients with localized prostate cancer treated with high-dose radiotherapy, including image-guided, intensity-modulated radiotherapy or brachytherapy with a median follow-up of 80.7 months. Overall survival rate was no different between ADT (+) and ADT (−) group in high-, intermediate-, and low-risk groups. OCM was found in 71 patients, consisting of 4% (10/258) in the ADT (−) group and 7% (61/858) in the ADT (+) group (p = 0.0422). The 10-year OCM-free survival rate (OCMFS), if divided by the duration of ADT (ADT naïve (ADT (−)), ADT <2-year, and ADT ≥2-year groups), showed statistical significance, and was 90.7%, 88.2%, and 78.6% (p = 0.0039) for the ADT (−), ADT <2-year, and ADT ≥2-year groups, respectively. In patients aged ≥75 years, 10-year OCMFS for ADT (−), ADT <2-, and ADT ≥2-year groups was 93.5% (at 115.6 months), 85.6%, and 60.7% (p = 0.0189), respectively, whereas it was 90.7%, 89.9%, and 89.0% (p = 0.4716), respectively, in their younger counterparts. In localized prostate cancer patients, treatment with longer ADT for ≥2 years potentially increases the risk of OCM, especially in patients aged ≥75 years.

A phase III trial of short-term androgen deprivation therapy in intermediate-risk prostate cancer treated with radiotherapy.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5019-5019 ◽  
Author(s):  
Abdenour Nabid ◽  
Nathalie Carrier ◽  
Eric Vigneault ◽  
Luis Souhami ◽  
Céline Lemaire ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Intermediate Risk ◽  
Short Term ◽  
Phase Iii Trial ◽  
Risk Prostate Cancer
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