Dataset Information

A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

ABSTRACT:

Purpose

To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.

Methods

Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%). Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA). Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.

Results

Eighty eight miRNAs were identified to be significantly (p<0.05) associated with biochemical failure post-prostatectomy by multivariate analysis and clustered into two groups that correlated with early (? 36 months) versus late recurrence (>36 months). Nine miRNAs were identified to be significantly (p<0.05) associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC) was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone.

Conclusion

miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601) were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further validation studies.

SUBMITTER: Bell EH

PROVIDER: S-EPMC4356539 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

Bell Erica Hlavin EH Kirste Simon S Fleming Jessica L JL Stegmaier Petra P Drendel Vanessa V Mo Xiaokui X Ling Stella S Fabian Denise D Manring Isabel I Jilg Cordula A CA Schultze-Seemann Wolfgang W McNulty Maureen M Zynger Debra L DL Martin Douglas D White Julia J Werner Martin M Grosu Anca L AL Chakravarti Arnab A

PloS one 20150311 3

<h4>Purpose</h4>To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.<h4>Methods</h4>Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identif ...[more]

PMID: 25760964

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Project description:PurposeTo compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy.Methods and materialsA total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first.ResultsThe median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively.ConclusionsDose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.

Project description:BackgroundTreatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting.MethodsAn independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases.ResultsMedian age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%).ConclusionsIn our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA responders, however, with significant morbidity. Additionally, post-HIFU PSA nadir appears to be an important predictor for both progression and survival. Further research on focal salvage ablation in order to reduce toxicity while retaining disease control rates is required.

Dataset Information

A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

Purpose

Methods

Results

Conclusion

Publications

A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

Similar Datasets

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