scholarly journals Effect of Chemotherapy With Docetaxel With Androgen Suppression and Radiotherapy for Localized High-Risk Prostate Cancer: The Randomized Phase III NRG Oncology RTOG 0521 Trial

2019 ◽  
Vol 37 (14) ◽  
pp. 1159-1168 ◽  
Author(s):  
Seth A. Rosenthal ◽  
Chen Hu ◽  
Oliver Sartor ◽  
Leonard G. Gomella ◽  
Mahul B. Amin ◽  
...  

PURPOSE Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer. PATIENTS AND METHODS The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT. RESULTS A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided P = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 v 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided P = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.76; 95% CI, 0.58 to 0.99; two-sided P = .043). CONCLUSION For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 374-374
Author(s):  
Ray Manneh Kopp ◽  
Mauricio Lema ◽  
Linda Ibatá

374 Background: In order to improve long term results for high-risk prostate cancer, several clinical trials have tested the addition of docetaxel chemotherapy. The outcomes of this trials have not led to clear conclusions. We conducted a meta-analysis of randomized phase 3 trials testing the efficacy of docetaxel after radiotherapy in high risk prostate cancer patients. Methods: A systematic review of PubMed (Medline), Embase and the Cochrane Library was conducted. We followed the PRISMA guidelines, three investigators independently selected the articles and verified inclusion criteria. We compared the overall survival and disease-free survival between the intervention group (adjuvant chemotherapy with docetaxel) and the control group (without adjuvant chemotherapy) by calculating the hazard ratio (HR) with 95% confidence intervals (CIs). Pooled effects were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: 382 publications were identified, four phase III trials (STAMPEDE, RTOG0521, SPCG-13, GETUG 12) comparing docetaxel vs standard of care after radiotherapy for high-risk prostate cancer fulfilled the inclusion criteria with data from 2034 patients (1135 in placebo group and 899 in adjuvant docetaxel group). Heterogeneity was not found between the included studies for OS (I 2 0%), but it was found between studies for disease-free survival (I2 60%). Adjuvant docetaxel chemotherapy showed overall survival benefit when compared to ADT alone (HR 0,72 95% CI 0,54-0,96). Adjuvant docetaxel also improved the disease-free survival when compared to ADT alone (HR 0,74 95% CI 0,64-0,86). No evidence of publication bias was observed. Conclusions: This meta-analysis shows that docetaxel after definitive radiotherapy in high-risk prostate cancer is likely to be more effective than standard of care in terms of overall survival and disease-free survival. Further prospective studies are needed in order to increase the sample that would lead to show a more robust data.


2021 ◽  
Vol 11 ◽  
Author(s):  
Stine Elleberg Petersen ◽  
Morten Høyer

PurposeThere is high-level evidence for addition of androgen deprivation therapy to photon-based radiotherapy of the prostate in intermediate- and high-risk prostate cancer. Little is known about the value of ADT in particle therapy of prostate cancer. We are conducting a systematic review on biochemical disease-free survival, overall survival, and morbidity after combined particle therapy and ADT for prostate cancer.MethodsA thorough search in PubMed, Embase, Scopus, and Web of Science databases were conducted, searching for relevant studies. Clinical studies on prostate cancer and the treatment combination of particle therapy and androgen deprivation therapy were included. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD42021230801).ResultsA total of 298 papers were identified. Fifteen papers reporting on 7,202 patients after proton or carbon-ion therapy for localized prostate cancer where a fraction or all patients received ADT were selected for analysis. Three thousand five hundred and nineteen (49%) of the patients had received combined ADT and particle therapy. Primarily high-risk (87%), to a lesser extent intermediate-risk (34%) and low-risk patients (12%) received ADT. There were no comparative studies on the effect of ADT in patients treated with particles and no studies identified ADT as an independent prognostic factor related to survival outcomes.ConclusionsThe review found no evidence to support that the effects on biochemical disease-free survival and morbidity of combining ADT to particle therapy differs from the ADT effects in conventional photon based radiotherapy. The available data on the topic is limited.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3486
Author(s):  
Hideya Yamazaki ◽  
Gen Suzuki ◽  
Koji Masui ◽  
Norihiro Aibe ◽  
Daisuke Shimizu ◽  
...  

This study aimed to examine the role of very high-risk (VHR) factors (T3b–4 and Gleason score 9–10) for prognosis of clinically localized high-risk prostate cancer. We reviewed multi-institutional retrospective data of 1413 patients treated with radiotherapy (558 patients treated with external beam radiotherapy (EBRT) and 855 patients treated with brachytherapy (BT) ± EBRT. We introduced an index by simple summation of the number of VHR factors—VHR-0, VHR-1, and VHR-2. With median follow-up of 69.6 months, the 5-year biochemical disease free survival rate (bDFS), prostate cancer-specific mortality (PCSM), and distant metastasis-free survival (DMSF) rates were 59.4%, 7.65%, and 83.2% for the VHR-2 group, respectively; 86.7%, 1.50%, and 95.4% for the VHR-1 group, respectively; and 93.1%, 0.12%, and 98.2% for the VHR-0 group, respectively. The VHR-2 group had significantly worse bDFS, PCSM, and DMSF than the VHR-0 (hazard ratios: 4.55, 9.607, and 7.904, respectively) and VHR-1 (hazard ratios: 1.723, 2.391, and 1.491, respectively) groups. The VHR-2 group could be identified as a super high-risk group compared with other groups, and could be a good candidate for clinical trials using multimodal intensified treatments. Simple summation of the number of VHR factors is an easy and useful predictive index for bDFS, PCSM, and DMSF.


2021 ◽  
Author(s):  
Yong Seong Lee ◽  
Tae Young Shin

Abstract Background Robot-assisted radical prostatectomy (RARP) is an acceptable procedure for localized prostate cancer. However, RARP has not been offered to patients with high-risk prostate cancer. We report long-term functional and oncologic outcomes of patients who underwent RARP for clinically high-risk prostate cancer and to assess the role of RARP in patients with high-risk prostate cancer. Methods This study included 90 patients with high-risk prostate cancer according to the D'Amico criteria who underwent RARP between January 2014 and December 2019. High risk was based on the presence of a clinical stage of ≥ T2c, a pretreatment prostate-specific antigen level > 20 ng/mL, or a biopsy Gleason score ≥ 8. Functional outcomes including postoperative continence and potency were assessed at 1, 3, 6, and 12 months after RARP. Oncologic outcomes comprised positive surgical margins (PSMs), biochemical recurrence (BCR), BCR-free survival, and clinical recurrence (CR)-free survival rates at 1 and 3 years. Results The median operative time was 185 (interquartile range [IQR], 140–250) minutes. Based on postoperative pathology, the rates of PSMs in the entire cohort and in those with stage pT2 disease were 27.8% and 8.9%, respectively. The continence and potency rates at 12 months were 87.8% and 56.7%, respectively. The BCR rate was 23.3%, and the median time to BCR was 10.5 (IQR, 3.5–26.9) months. The 1- and 3-year BCR-free survival rates were 91.5% and 85.5%, respectively, and the 1- and 3-year CR-free survival rates were 97.5% and 90.8%, respectively. Conclusions Most patients with clinically high-risk prostate cancer treated with RARP remained BCR-free and CR-free during the long-term follow-up. The optimal functional and oncologic outcomes indicating RARP as a safe and feasible approach in the present study should be confirmed in future studies.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248461
Author(s):  
Jae-Uk Jeong ◽  
Taek-Keun Nam ◽  
Ju-Young Song ◽  
Mee Sun Yoon ◽  
Sung-Ja Ahn ◽  
...  

Introduction To determine the prognostic significance of long-term adjuvant androgen deprivation therapy (A-ADT) over 1 year in achieving undetectable levels of prostate-specific antigen (PSA) less than 0.001 ng/mL in prostate cancer patients with high- or very high-risk prostate cancer who underwent radiotherapy (RT). Materials and methods A total of 197 patients with prostate cancer received RT, with a follow-up of ≥12 months. Biochemical failure was defined as PSA ≥nadir + 2 ng/mL after RT. We analyzed clinical outcomes, including survival, failure patterns, and prognostic factors affecting outcomes. Results Biochemical failure-free survival (BCFFS), clinical failure-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival (OS) rates at 5 years were 91.1%, 95.4%, 96.9%, 99.5%, and 89.1%, respectively. Administration of long-term A-ADT significantly predicted favorable BCFFS (p = 0.027) and OS (p < 0.001) in multivariate analysis. Nadir PSA ≤0.001 ng/mL was an independent prognostic factor for BCFFS (p = 0.006) and OS (p = 0.021). The use of long-term A-ADT significantly affected nadir PSA ≤0.001 ng/mL (p < 0.001). The patients with A-ADT for 1 year or longer had better BCFFS or OS than those for less than 1 year or those without A-ADT (p < 0.001). The best prognosis was demonstrated in patients treated with long-term A-ADT and nadir PSA ≤0.001 ng/mL in BCFFS (p < 0.001). Conclusion The addition of long-term A-ADT over 1 year to RT demonstrated good treatment outcomes in patients with locally advanced prostate cancer. Achieving a nadir PSA value ≤0.001 ng/mL using combination therapy with RT and A-ADT is a powerful clinical predictor of treatment outcomes.


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