Dataset Information

Integrating Serum Biomarkers into Prediction Models for Biochemical Recurrence Following Radical Prostatectomy.

ABSTRACT: This study undertook to predict biochemical recurrence (BCR) in prostate cancer patients after radical prostatectomy using serum biomarkers and clinical features. Three radical prostatectomy cohorts were used to build and validate a model of clinical variables and serum biomarkers to predict BCR. The Cox proportional hazard model with stepwise selection technique was used to develop the model. Model evaluation was quantified by the AUC, calibration, and decision curve analysis. Cross-validation techniques were used to prevent overfitting in the Irish training cohort, and the Austrian and Norwegian independent cohorts were used as validation cohorts. The integration of serum biomarkers with the clinical variables (AUC = 0.695) improved significantly the predictive ability of BCR compared to the clinical variables (AUC = 0.604) or biomarkers alone (AUC = 0.573). This model was well calibrated and demonstrated a significant improvement in the predictive ability in the Austrian and Norwegian validation cohorts (AUC of 0.724 and 0.606), compared to the clinical model (AUC of 0.665 and 0.511). This study shows that the pre-operative biomarker PEDF can improve the accuracy of the clinical factors to predict BCR. This model can be employed prior to treatment and could improve clinical decision making, impacting on patients' outcomes and quality of life.

SUBMITTER: Moghaddam S

PROVIDER: S-EPMC8391749 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Integrating Serum Biomarkers into Prediction Models for Biochemical Recurrence Following Radical Prostatectomy.

Moghaddam Shirin S Jalali Amirhossein A O'Neill Amanda A Murphy Lisa L Gorman Laura L Reilly Anne-Marie AM Heffernan Áine Á Lynch Thomas T Power Richard R O'Malley Kieran J KJ Taskèn Kristin A KA Berge Viktor V Solhaug Vivi-Ann VA Klocker Helmut H Murphy T Brendan TB Watson R William RW

Cancers 20210819 16

This study undertook to predict biochemical recurrence (BCR) in prostate cancer patients after radical prostatectomy using serum biomarkers and clinical features. Three radical prostatectomy cohorts were used to build and validate a model of clinical variables and serum biomarkers to predict BCR. The Cox proportional hazard model with stepwise selection technique was used to develop the model. Model evaluation was quantified by the AUC, calibration, and decision curve analysis. Cross-validation ...[more]

PMID: 34439316

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Project description:ImportanceStratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments.ObjectiveTo evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM.Design, setting, and participantsThis population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023.Main outcomes and measuresPrimary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria.ExposuresRadical prostatectomy or radiotherapy.ResultsA total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category.Conclusions and relevanceThese findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.

Project description:ObjectivesTo construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour.Patients and methodsPatients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence-free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre- and post-surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA-PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria.ResultsData from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3-year BRFS for both pre- and post-surgical models. SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 66% to 42% for a patient aged 65 years with typical pre-surgical parameters (PSA level 8 ng/mL, Prostate Imaging-Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post-surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed.ConclusionTumour SUVmax on diagnostic PSMA-PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP.

Project description:The objective of this study was to utilize a microarray platform to determine the microRNA (miRNA) expression profile in prostate cancer tissue from patients who underwent radical prostatectomy and were followed for an average of 47 months. The GeneChip® miRNA Array (Affymetrix) contains more than 46,000 probes, and more than 1,100 mature human miRNAs and transcripts. An expression level higher or lower than 1.1 with a p<0.05 were considered to be differentially expressed. When tumors with a GS<7 were compared with those with a GS≥7, five miRNAs were down-regulated and nine were up-regulated. In comparing tumors from patients with PSA <10 ng/mL vs. those with PSA ≥10 ng/mL, 21 miRNAs were down-regulated and 29 were overexpressed. There was decreased expression of 21 miRNAs and increased expression of 22 miRNAs when pT2 and pT3 tumors were compared. The comparison of the expression profiles of men with vs. without recurrent disease (PSA>0.2 ng/mL) revealed that 14 miRNAs were down-regulated and 17 were up-regulated. Considering the three prognostic factors and biochemical recurrence, miR-335 was overexpressed in pT3 tumors in patients with PSA>10 ng/mL, miR-1202 was overexpressed in recurrent tumors in which PSA >10 ng/mL, and miR-885 and miR-1226 were overexpressed in recurrent pT3 tumors. Six miRNAs (miR- 361, 378, 548, 574, 652 and 892) had decreased expression in pT3 tumors in patients with PSA >10 ng/mL. miR-16 was down-regulated in recurrent pT3 tumors. miR-92 and miR-450 exhibited decreased expression in recurrent tumors in patients with PSA > 10 ng/mL. miR-28 was down-regulated in pT3 adenocarcinomas with a GS ≥ 7. The differentially expressed miRNAs in recurrent tumors were validated using qRT-PCR in 74 additional specimens. miR-21 was overexpressed in recurrent tumors, and in the Cox model, expression levels higher than 0.64 were indicative of biochemical recurrence with a risk of 2.4. These results, which were based on clinical specimens from patients treated in a standardized way and followed for an average of 47 months, provide an initial understanding of the role of miRNAs in prostatecancer progression; the foremost representative is miR-21, which has been implicated in the progression of various human cancers.

Project description:The objective of this study was to utilize a microarray platform to determine the microRNA (miRNA) expression profile in prostate cancer tissue from patients who underwent radical prostatectomy and were followed for an average of 47 months. The GeneChipM-BM-. miRNA Array (Affymetrix) contains more than 46,000 probes, and more than 1,100 mature human miRNAs and transcripts. An expression level higher or lower than 1.1 with a p<0.05 were considered to be differentially expressed. When tumors with a GS<7 were compared with those with a GSM-bM-^IM-%7, five miRNAs were down-regulated and nine were up-regulated. In comparing tumors from patients with PSA <10 ng/mL vs. those with PSA M-bM-^IM-%10 ng/mL, 21 miRNAs were down-regulated and 29 were overexpressed. There was decreased expression of 21 miRNAs and increased expression of 22 miRNAs when pT2 and pT3 tumors were compared. The comparison of the expression profiles of men with vs. without recurrent disease (PSA>0.2 ng/mL) revealed that 14 miRNAs were down-regulated and 17 were up-regulated. Considering the three prognostic factors and biochemical recurrence, miR-335 was overexpressed in pT3 tumors in patients with PSA>10 ng/mL, miR-1202 was overexpressed in recurrent tumors in which PSA >10 ng/mL, and miR-885 and miR-1226 were overexpressed in recurrent pT3 tumors. Six miRNAs (miR- 361, 378, 548, 574, 652 and 892) had decreased expression in pT3 tumors in patients with PSA >10 ng/mL. miR-16 was down-regulated in recurrent pT3 tumors. miR-92 and miR-450 exhibited decreased expression in recurrent tumors in patients with PSA > 10 ng/mL. miR-28 was down-regulated in pT3 adenocarcinomas with a GS M-bM-^IM-% 7. The differentially expressed miRNAs in recurrent tumors were validated using qRT-PCR in 74 additional specimens. miR-21 was overexpressed in recurrent tumors, and in the Cox model, expression levels higher than 0.64 were indicative of biochemical recurrence with a risk of 2.4. These results, which were based on clinical specimens from patients treated in a standardized way and followed for an average of 47 months, provide an initial understanding of the role of miRNAs in prostatecancer progression; the foremost representative is miR-21, which has been implicated in the progression of various human cancers. Fifty-three patients underwent a radical prostatectomy performed by the same surgeon (MS) to treat localized PC between August 2000 and June 2002. The mean age was 65 years (SD: 7.5, range: 49 - 77). The mean Gleason score was 7 (SD: 1.1, range: 5 - 10); 15 tumors had a score of 5 or 6, and 38 had a score between 7 and 10. Twenty-four (45.3%) of the patients had pT2 tumors, and 29 (54.7%) had pT3 tumors. The control group consisted of three patients with lower urinary tract symptoms, a mean age of 55.3 years and a diagnosis of benign prostatic hyperplasia (BPH) who consented to open surgery.

Dataset Information

Integrating Serum Biomarkers into Prediction Models for Biochemical Recurrence Following Radical Prostatectomy.

Publications

Integrating Serum Biomarkers into Prediction Models for Biochemical Recurrence Following Radical Prostatectomy.

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