Dataset Information

Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials.

ABSTRACT:

Background

The importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.

Objective

To evaluate the clinical implications of LF after definitive RT.

Design, setting, and participants

Individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.

Outcome measurements and statistical analysis

Multivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints.

Results and limitations

Median follow-up was 6.4?yr overall and 7.2?yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37-2.10]), PCSS (3.10 [95% CI 2.33-4.12]), and DMFS (HR 1.92 [95% CI 1.54-2.39]), p?ConclusionsLF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. LF events warrant consideration for intervention, potentially suggesting a rationale for upfront treatment intensification. However, whether these findings apply to all men or just those without significant comorbidity remains to be determined.

Patient summary

Men who experience a local recurrence of high-grade prostate cancer after receiving upfront radiation therapy are at significantly increased risks of developing metastases and dying of prostate cancer.

SUBMITTER: Kishan AU

PROVIDER: S-EPMC7008470 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials.

Kishan Amar U AU Chu Fang-I FI King Christopher R CR Seiferheld Wendy W Spratt Daniel E DE Tran Phuoc P Wang Xiaoyan X Pugh Stephanie E SE Sandler Kiri A KA Bolla Michel M Maingon Philippe P De Reijke Theo T Nickols Nicholas G NG Rettig Matthew M Drakaki Alexandra A Liu Sandy T ST Reiter Robert E RE Chang Albert J AJ Feng Felix Y FY Sajed Dipti D Nguyen Paul L PL Kupelian Patrick A PA Steinberg Michael L ML Boutros Paul C PC Elashoff David D Collette Laurence L Sandler Howard M HM

European urology 20191110 2

<h4>Background</h4>The importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.<h4>Objective</h4>To evaluate the clinical implications of LF after definitive RT.<h4>Design, setting, and participants</h4>Individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.<h4>Outcome measurements and statistical analysis</h4>Multivariable Cox pro ...[more]

PMID: 31718822

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Project description:BACKGROUND:Prostate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men. OBJECTIVE:To determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men. DESIGN, SETTING, AND PARTICIPANTS:Nested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A prospective cohort in the southeastern USA with recruitment from community health centers. A total of 197 incident PCa patients aged 40-64 yr at study entry and 569 controls matched on age, date of blood draw, and site of enrollment. Total PSA was measured in blood collected and stored at enrollment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Total and aggressive PCa (91 aggressive: Gleason ?7, American Joint Committee on Cancer stage III/IV, or PCa-specific death). Exact conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) for PCa by category of baseline PSA. RESULTS AND LIMITATIONS:Median PSA among controls was 0.72, 0.80, 0.94, and 1.03ng/ml for age groups 40-49, 50-54, 55-59, and 60-64 yr, respectively; 90th percentile levels were 1.68, 1.85, 2.73, and 3.33ng/ml. Furthermore, 95% of total and 97% of aggressive cases had baseline PSA above the age-specific median. Median follow-up was 9 yr. The OR for total PCa comparing PSA >90th percentile versus ?median was 83.6 (95% CI, 21.2-539) for 40-54 yr and 71.7 (95% CI, 23.3-288) for 55-64 yr. For aggressive cancer, ORs were 174 (95% CI, 32.3-infinity) for 40-54 yr and 51.8 (95% CI, 11.0-519) for 55-64 yr. A composite endpoint of aggressive PCa based on stage, grade, and mortality was used and is a limitation. CONCLUSIONS:PSA levels in midlife strongly predicted total and aggressive PCa among black men. PSA levels among controls were similar to those among white controls in prior studies. PATIENT SUMMARY:Prostate-specific antigen (PSA) level during midlife strongly predicted future development of aggressive prostate cancer among black men. Targeted screening based on a midlife PSA might identify men at high risk while minimizing screening in those men at low risk.

Project description:BackgroundObservational data has indicated improved survival after radical prostatectomy (RP) compared with definitive radiotherapy (RT) in men with high-risk prostate cancer (PCa).ObjectiveTo compare PCa-specific mortality (PCSM) and overall mortality (OM) in men with high-risk PCa treated with RP or RT, providing information on target doses and fractionations.Design setting and participantsThis is an observational study from the Cancer Registry of Norway. Patients were diagnosed with high-risk PCa during 2006-2015, treated with RP ≤12 mo or RT ≤15 mo after diagnosis, and stratified according to RP or RT modality; external beam radiotherapy (EBRT; 70-<74, 74-<78, or 78 Gy), hypofractionated RT or EBRT combined with brachytherapy (BT-RT).Outcome measurements and statistical analysisCompeting risk and Kaplan-Meier methods estimated PCSM and OM, respectively. Multivariable Cox regression models evaluated hazard ratios (HRs) for PCSM and OM.Results and limitationsIn total, 9254 patients were included (RP 47%, RT 53%). RT patients were older, had poorer performance status and more unfavorable disease characteristics. With a median follow-up time of seven and eight yrs, the overall 10-yr PCSM was 7.2% (95% confidence interval [CI] 6.4-8.0) and OM was 22.9% (95% CI 21.8-24.1). Compared with RP, EBRT 70-<74 Gy was associated with increased (HR 1.88, 95% CI 1.33-2.65, p < 0.001) and BT-RT with decreased (HR 0.49, 95% CI 0.24-0.96, p = 0.039) 10-yr PCSM. Patients treated with EBRT 70-78 Gy had higher adjusted 10-yr OM than those treated with RP.ConclusionsIn men with high-risk PCa, treatment with EBRT <74 Gy was associated with increased adjusted 10-yr PCSM and OM, and BT-RT with decreased 10-yr PCSM, compared with RP.Patient summaryIn this study, we compared mortality after radical prostatectomy (RP) and radiotherapy (RT) in men with high-risk prostate cancer (PCa); the results suggest that men receiving lower-dose RT have higher, and patients receiving brachytherapy may have lower, risk of death from PCa than patients treated with prostatectomy.

Dataset Information

Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials.

Background

Objective

Design, setting, and participants

Outcome measurements and statistical analysis

Results and limitations

Patient summary

Publications

Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials.

Similar Datasets

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