Dataset Information

Outcomes following radical prostatectomy or external beam radiation for veterans with Gleason 9 and 10 prostate cancer.

ABSTRACT:

Background

The optimal upfront treatment modality for patients with nonmetastatic Gleason Score 9 and 10 prostate cancer (GS 9-10 PCa) is unknown.

Methods

We conducted a retrospective cohort study of patients in the Veterans Health Administration (VHA) with GS 9-10 PCa treated with radical prostatectomy (RP) or external beam radiation therapy with androgen deprivation therapy (EBRT+ADT) from 1/2000 to 12/2010. Outcomes included overall survival (OS), distant metastasis-free survival (DMFS), and salvage/adjuvant therapy-free survival (SAFS), as assessed by Kaplan-Meier analysis.

Results

We identified 1220 veterans with GS 9-10 PCa; 335 were treated with RP, and 885 were treated with EBRT+ADT. With a median follow-up of 9.9 years, propensity score-matched analyses demonstrated that RP had superior 10-year OS (70.8% [RP] vs. 61.2% [EBRT+ADT], p < 0.001), 10-year DMFS rates were similar between RP (76.7%) and EBRT+ADT (81.0%), and 10-year SAFS rates were lower for RP vs EBRT + ADT (35.2% [RP] vs. 75.2% [EBRT+ADT], p < 0.001). The receipt of salvage ADT was higher with upfront RP (51.9% vs. 26.1%, p < 0.001), despite receipt of adjuvant/salvage EBRT in 41.8% of RP patients. Among patients treated with RP, there were no differences in outcomes by race. However, higher survival rates were noted among Black patients treated with EBRT+ADT compared with White patients.

Conclusions

This analysis demonstrated higher 10-year OS rates among men treated with upfront RP versus EBRT+ADT, though missing confounders and similar DMFS rates suggest the long-term cause-specific OS rates may be similar. We also highlight real-world outcomes of a diverse patient population in the VHA and improved outcomes for Black patients receiving EBRT+ADT.

SUBMITTER: Chao HH

PROVIDER: S-EPMC9359878 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Outcomes following radical prostatectomy or external beam radiation for veterans with Gleason 9 and 10 prostate cancer.

Chao Hann-Hsiang HH Soni Payal D PD Dahman Bassam B Stilianoudakis Spiro C SC Ford Hampton H Singh Raj R Freedland Stephen J SJ Moghanaki Drew D Vapiwala Neha N Chang Michael G MG

Cancer medicine 20220315 15

<h4>Background</h4>The optimal upfront treatment modality for patients with nonmetastatic Gleason Score 9 and 10 prostate cancer (GS 9-10 PCa) is unknown.<h4>Methods</h4>We conducted a retrospective cohort study of patients in the Veterans Health Administration (VHA) with GS 9-10 PCa treated with radical prostatectomy (RP) or external beam radiation therapy with androgen deprivation therapy (EBRT+ADT) from 1/2000 to 12/2010. Outcomes included overall survival (OS), distant metastasis-free surviv ...[more]

PMID: 35289111

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Project description:Importance:The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective:To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants:Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures:Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures:The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results:Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance:Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Project description:We assessed survival after radical prostatectomy, intensity modulated radiation therapy or conformal radiation therapy vs no local therapy for metastatic prostate cancer adjusting for patient comorbidity, androgen deprivation therapy and other factors.We identified men 66 years old or older with metastatic prostate cancer treated with radical prostatectomy, intensity modulated radiation therapy, conformal radiation therapy or no local therapy in the SEER-Medicare linked database from 2004 to 2009. Multivariable Cox proportional hazards models before and after inverse propensity score weighting were used to assess all cause and prostate cancer specific mortality. Competing risk regression analysis was done to assess prostate cancer specific mortality.Of 4,069 men with metastatic prostate cancer radical prostatectomy in 47, intensity modulated radiation therapy in 88 and conformal radiation therapy in 107 were selected as local therapy vs no local therapy in 3,827. Radical prostatectomy was associated with a 52% decrease (HR 0.48, 95% CI 0.27-0.85) in the risk of prostate cancer specific mortality after adjusting for sociodemographics, primary tumor characteristics, comorbidity, androgen deprivation therapy and bone radiation within 6 months of diagnosis. Intensity modulated radiation therapy was associated with a 62% decrease (HR 0.38, 95% CI 0.24-0.61) in the risk of prostate specific cancer specific mortality. Conformal radiation therapy was not associated with improved survival compared to no local therapy. Propensity score weighting yielded comparable results. Competing risk analysis revealed a 42% and 57% decrease (SHR 0.58, 95% CI 0.35-0.95 and SHR 0.43, 95% CI 0.27-0.68, respectively) in the risk of prostate cancer specific mortality for radical prostatectomy and intensity modulated radiation therapy.Local therapy with radical prostatectomy and intensity modulated radiation therapy but not with conformal radiation therapy was associated with a survival benefit in men with metastatic prostate cancer. This finding warrants prospective evaluation in clinical trials.

Project description:PURPOSE:Very high-risk prostate cancer (PC) is associated with poor response to local and systemic treatments; however, few cases have been molecularly profiled. We studied clinical outcomes and molecular profiles of patients with clinically localized primary Gleason pattern 5 PC. PATIENTS AND METHODS:Clinicopathologic features, targeted somatic and germline sequencing, and PTEN, TP53, and ERG status by immunohistochemistry were assessed in patients undergoing surgery from 2005 to 2015; 60 consecutive patients were identified with Gleason score 5 + 4 = 9 or 5 + 5 = 10 PC after radical prostatectomy with available tissue and clinical follow-up. Clinicopathologic and genomic parameters were correlated with biochemical relapse, metastasis-free survival, time to castration resistance, and overall survival using Cox proportional hazards models. RESULTS:Of patients with somatic sequencing data and clinical follow-up, 34% had DNA repair gene mutations, including 22% (11 of 49) with homologous recombination and 12% (six of 49) with mismatch repair gene alterations. Homologous recombination mutations were germline in 82% (nine of 11) of patients. In addition, 33% (16 of 49) had TP53 mutation, and 51% (29 of 57) had PTEN loss. Overall, 43% developed metastasis, with a time to castration resistance of 12 months. On multivariable analysis of clinicopathologic variables, only ductal/intraductal histology (hazard ratio, 4.43; 95% CI, 1.76 to 11.15; P = .002) and seminal vesicle invasion (hazard ratio, 5.14; 95% CI, 1.83 to 14.47; P = .002) were associated with metastasis. Among genomic alterations, only TP53 mutation and PTEN loss were associated with metastasis on univariable analysis, and neither remained significant in multivariable analyses. These data are retrospective and hypothesis generating. CONCLUSION:Potentially actionable homologous recombination and mismatch repair alterations are observed in a significant proportion of patients with very high-risk PC at the time of radical prostatectomy. These findings could inform the design of prospective trials in this patient population.

Project description:The time and speed of biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) is highly variable. Stratification methods based on TNM staging and Gleason score (GS) do not allow the identification of patients at risk of BCR following RP. Therefore, the aim of the present study was to identify molecular signatures that can predict BCR risk effectively and facilitate treatment-related decisions for patients with PCa. RNA sequencing data and corresponding clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Oncomine databases. Bioinformatics analysis was performed to identify differentially expressed genes in patients with GS=6 and GS ≥7. Cox regression models were used to determine the PCa signature (PCasig) and a clinical nomogram for the prediction of BCR. The performance of nomograms was assessed using time-dependent receiver operating characteristic curves and the concordance index (C-index). A PCasig comprising 10 genes, including SEMG2, KCNJ16, TFAP2B, SYCE1, KCNU1, AFP, GUCY1B2, GRIA4, NXPH1 and SOX11, was significantly associated with BCR, which was identified in TCGA cohort [hazard ratio (HR), 5.18; 95% CI, 3.241-8.272; C-index, 0.777] and validated in the Oncomine cohort (HR, 2.78; 95% CI, 1.39-5.54; C-index, 0.66). The expression levels of SEMG2, KCNJ16 and TFAP2B were downregulated in patients with GS ≥7. The expression levels of SYCE1, KCNU1, AFP, GUCY1B2, GRIA4, NXPH1 and SOX11 were upregulated in patients with GS ≥7. The clinical nomogram was constructed based on the GS and pathologic T stage (HR, 4.15; 95% CI, 1.39-5.54; C-index, 0.713). The addition of the PCasig to the clinical nomogram significantly improved prognostic value (HR, 7.25; 95% CI, 4.54-11.56; C-index, 0.782) with an net reclassification improvement of 75.3% (95% CI, 46.8-104.6%). Furthermore, the endogenous expression of each gene in the PCasig was measured in five PCa cell lines and in normal prostate cells, and these genes exhibited different expression levels relative to one another. In conclusion, an PCasig was identified by mining TCGA and successfully validated in an Oncomine cohort. This PCasig was an independent prognostic factor with a greater prognostic value for all patients regardless of GS than traditional clinical variables, which can improve the performance of clinical nomograms in predicting BCR of patients with GS ≥7.

Dataset Information

Outcomes following radical prostatectomy or external beam radiation for veterans with Gleason 9 and 10 prostate cancer.

Background

Methods

Results

Conclusions

Publications

Outcomes following radical prostatectomy or external beam radiation for veterans with Gleason 9 and 10 prostate cancer.

Similar Datasets

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