Dataset Information

Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy.

ABSTRACT:

Background

Clinical 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 methods

This 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.

Results

Median 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).

Conclusions

MFS 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.

SUBMITTER: Schweizer MT

PROVIDER: S-EPMC3888237 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy.

Schweizer M T MT Zhou X C XC Wang H H Yang T T Shaukat F F Partin A W AW Eisenberger M A MA Antonarakis E S ES Antonarakis E S ES

Annals of oncology : official journal of the European Society for Medical Oncology 20130814 11

<h4>Background</h4>Clinical 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.<h4>Patients and methods</h4>This 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 metas ...[more]

PMID: 23946329

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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.

Project description:ImportanceVery high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment-resources more readily available at high-volume centers.ObjectiveTo examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer.Design, setting, and participantsA retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, >4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016.ExposuresTreatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient's treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test.Main outcomes and measuresOverall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards.ResultsA total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers (P < .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P < .001). These results were also significant after inverse probability score weighted-based adjustment.Conclusions and relevanceIn this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.

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Project description:ImportanceLong-term control of node-positive (N1) prostate cancer, the incidence of which is increasing, is obtainable with aggressive treatment, and definitive external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT) is an increasingly preferred option. Caring for these patients is complex and may require resources more readily available at high-volume centers.ObjectiveTo evaluate the association between radiation facility case volume and overall survival (OS) in men with N1 prostate cancer.Design, setting, and participantsThis cohort study included 1899 men diagnosed with T1N1M0 to T4N1M0 prostate cancer treated with curative-intent EBRT and ADT between January 2004 and December 2016 at US facilities reporting to the National Cancer Database. Data analysis was performed from March to June 2020.ExposuresTreatment at a center with high vs low average cumulative facility volume (ACFV), defined as the total number of prostate radiation cases at an individual patient's treatment facility from 2004 until the year of that patient's diagnosis.Main outcomes and measuresOS was assessed between high- vs low-ACFV centers using the Kaplan-Meier method with and without propensity score-based weighted adjustment and multivariable Cox proportional hazards. The nonlinear association between continuous ACFV and OS was examined through a Martingale residual plot, and the optimal ACFV cutoff point that maximized the separation between high vs low ACFV was identified via a bias adjusted log rank test.ResultsA total of 1899 men met inclusion criteria. The median (interquartile range) age was 66 (60-72) years, 1491 (78.5%) were White individuals, and 1145 (60.3%) were treated at nonacademic centers. The optimal ACFV cutoff point was 66.4 patients treated per year. The median OS for patients treated at high-ACFV vs low-ACFV centers was 111.1 (95% CI, 101.5-127.9) months and 92.3 (95% CI, 87.7-103.9) months, respectively (P = .01). On multivariable analysis, treatment at a low-ACFV center was associated with increased risk of death (HR, 1.22; 95% CI, 1.02-1.46, P = .03) compared with treatment at a high-ACFV center. These results persisted after propensity score-based adjustment.Conclusions and relevanceThis cohort study found a significant association of facility case volume with long-term outcomes in men with N1 prostate cancer undergoing EBRT with ADT. Specifically, treatment at a facility with high radiation case volume was independently associated with longer OS. Further studies should focus on identifying which factors unique to high-volume centers may be responsible for this benefit.

Dataset Information

Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy.

Background

Patients and methods

Results

Conclusions

Publications

Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy.

Similar Datasets

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