Dataset Information

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

ABSTRACT:

Background

To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF).

Methods

422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n=111), minimal residual disease (MRD) SRT (n=70) and SRT (n=83) were defined by PSA levels of <0.2, 0.2-0.49 and ?0.5?ng?ml(-1), respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome.

Results

During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P<0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P=0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high.

Conclusions

The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.

SUBMITTER: Ross AE

PROVIDER: S-EPMC5411670 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Publications

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

Ross A E AE Den R B RB Yousefi K K Trock B J BJ Tosoian J J Davicioni E E Thompson D J S DJ Choeurng V V Haddad Z Z Tran P T PT Trabulsi E J EJ Gomella L G LG Lallas C D CD Abdollah F F Feng F Y FY Klein E A EA Dicker A P AP Freedland S J SJ Karnes R J RJ Schaeffer E M EM

Prostate cancer and prostatic diseases 20160503 3

<h4>Background</h4>To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF).<h4>Methods</h4>422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metast ...[more]

PMID: 27136742

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Project description:Risk prediction models that incorporate biomarkers and clinicopathologic variables may be used to improve decision making after radical prostatectomy (RP). We compared two previously validated post-RP classifiers-the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) and the Decipher genomic classifier (GC)-to predict prostate cancer-specific mortality (CSM) in a contemporary cohort of RP patients.To evaluate the combined prognostic ability of CAPRA-S and GC to predict CSM.A cohort of 1010 patients at high risk of recurrence after RP were treated at the Mayo Clinic between 2000 and 2006. High risk was defined by any of the following: preoperative prostate-specific antigen >20 ng/ml, pathologic Gleason score ?8, or stage pT3b. A case-cohort random sample identified 225 patients (with cases defined as patients who experienced CSM), among whom CAPRA-S and GC could be determined for 185 patients.The scores were evaluated individually and in combination using concordance index (c-index), decision curve analysis, reclassification, cumulative incidence, and Cox regression for the prediction of CSM.Among 185 men, 28 experienced CSM. The c-indices for CAPRA-S and GC were 0.75 (95% confidence interval [CI], 0.55-0.84) and 0.78 (95% CI, 0.68-0.87), respectively. GC showed higher net benefit on decision curve analysis, but a score combining CAPRA-S and GC did not improve the area under the receiver-operating characteristic curve after optimism-adjusted bootstrapping. In 82 patients stratified to high risk based on CAPRA-S score ?6, GC scores were likewise high risk for 33 patients, among whom 17 had CSM events. GC reclassified the remaining 49 men as low to intermediate risk; among these men, three CSM events were observed. In multivariable analysis, GC and CAPRA-S as continuous variables were independently prognostic of CSM, with hazard ratios (HRs) of 1.81 (p<0.001 per 0.1-unit change in score) and 1.36 (p=0.01 per 1-unit change in score). When categorized into risk groups, the multivariable HR for high CAPRA-S scores (?6) was 2.36 (p=0.04) and was 11.26 (p<0.001) for high GC scores (?0.6). For patients with both high GC and high CAPRA-S scores, the cumulative incidence of CSM was 45% at 10 yr. The study is limited by its retrospective design.Both GC and CAPRA-S were significant independent predictors of CSM. GC was shown to reclassify many men stratified to high risk based on CAPRA-S ?6 alone. Patients with both high GC and high CAPRA-S risk scores were at markedly elevated post-RP risk for lethal prostate cancer. If validated prospectively, these findings suggest that integration of a genomic-clinical classifier may enable better identification of those post-RP patients who should be considered for more aggressive secondary therapies and clinical trials.The Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) and the Decipher genomic classifier (GC) were significant independent predictors of prostate cancer-specific mortality. These findings suggest that integration of a genomic-clinical classifier may enable better identification of those post-radical prostatectomy patients who should be considered for more aggressive secondary therapies and clinical trials.

Project description:Simple Summary Meningiomas are the most common primary brain tumour and their prevalence increases in the ageing population. Among researchers, predicting surgical outcomes, complications, and quality of life (QoL) after surgery still represents a major subject of debate. The aim of the study hereby presented was to review well known and potential new prognostic factors affecting the early and long-term functional outcomes and quality of life of patients treated for intracranial meningiomas. Our findings might help define tailored surgical and perioperative protocols to maximise the standard of care, relying on a patient-specific multi-domain surgical, biometric, and clinical assessment to be conducted during the pre-operative medical interview. This approach might be beneficial for reducing complications occurrence, predicting surgical and functional outcomes, counselling patients and caregivers on surgical indications, reducing legal issues, and providing a valuable tool to healthcare providers for resources allocation. Abstract Object: To investigate those parameters affecting early and follow-up functional outcomes in patients undergoing resection of meningiomas and to design a dedicated predictive score, the Milan Bio(metric)-Surgical Score (MBSS) is hereby presented. Methods: Patients undergoing transcranial surgery for intracranial meningiomas were included. The most significant parameters in the regression analyses were implemented in a patient stratification score and were validated by testing its classification consistency with a clinical–radiological grading scale (CRGS), Milan complexity scale (MCS), and Charlson Comorbidity Index (CCI) scores. Results: The ASA score, Frailty index, skull base and posterior cranial fossa locations, a diameter of >25 mm, and the absence of a brain–tumour interface were predictive of early post-operative deterioration and were collected in MBSS Part A (AUC: 0.965; 95%C.I. 0.890–1.022), while the frailty index, posterior cranial fossa location, a diameter of >25 mm, a edema/tumour volume index of >2, dural sinus invasion, DWI hyperintensity, and the absence of a brain–tumour interface were predictive of a long-term unfavourable outcome and were collected in MBSS Part B (AUC: 0.877; 95%C.I. 0.811–0.942). The score was consistent with CRGS, MCS, and CCI. Conclusion: Patients’ multi-domain evaluation and the implementation of frailty indexes might help predict the perioperative complexity of cases; the functional, clinical, and neurological early outcomes; survival; and overall QoL after surgery.

Dataset Information

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

Background

Methods

Results

Conclusions

Publications

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

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