Long‐term cancer control outcomes in patients with biochemical recurrence and the impact of time from radical prostatectomy to biochemical recurrence

Pompe, Raisa S.; Gild, Philipp; Karakiewicz, Pierre I.; Bock, Lea-Philine; Schlomm, Thorsten; Steuber, Thomas; Graefen, Markus; Huland, Hartwig; Tian, Zhe; Tilki, Derya

doi:10.1002/pros.23511

Cited by 29 publications

(14 citation statements)

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“…Time to BCR is also crucial for CRD as this has already been demonstrated in our multivariable analysis ( p = 0.03). Similar results are found in other studies (12, 13, 37). Briganti et al (13) appropriately point out correlation between early BCR and CRD.…”

Section: Discussionsupporting

confidence: 93%

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Significance of Time Until PSA Recurrence After Radical Prostatectomy Without Neo- or Adjuvant Treatment to Clinical Progression and Cancer-Related Death in High-Risk Prostate Cancer Patients

2019

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Objective: The aim of our study was to evaluate the impact of time until biochemical recurrence (BCR) after radical prostatectomy (RP) without neo- or adjuvant treatment on clinical progression (CP) and cancer-related death (CRD) in high-risk prostate cancer (HRPCa) patients.Materials and methods: A total of 433 men with clinically HRPCa treated between 2001 and 2017 were identified. HRPCa was defined as clinical stage ≥T2c and/or biopsy Gleason score (GS) ≥8 and/or preoperative prostate specific antigen (PSA) value ≥20 ng/ml. Exclusion criteria were neo- or adjuvant treatment and incomplete pathological or follow-up data. BCR was defined as two consecutive PSA values ≥0.2 ng/ml after RP. CP was identified as skeletal lesions, local or loco-regional recurrence. CRD was defined as death from PCa. All men were divided into two groups according to BCR. The chi-square and t-tests were used to compare baseline characteristics between groups. Biochemical progression free survival (BPFS), clinical progression free survival (CPFS), and cancer-specific survival (CSS) rates were estimated using Kaplan–Meier analysis. Patients with detected BCR were analyzed for prediction of CP and CRD with respect to time until BCR. The impact of baseline parameters on BCR, CP, and CRD was assessed by Cox regression analysis.Results: BCR, CP, and CRD rates were 47.8% (207/433), 11.3% (49/433), and 5.5% (24/433), respectively. Median (quartiles) time of follow-up after RP was 64 (40–110) months. Ten-year BPFS rate was 34.2%; CPFS, 81%; and CSS, 90.1%. Men with detected BCR were analyzed for prediction of CP and CRD with respect to time until BCR. The most informative cutoff for time from RP until CP and CRD was ≤ 1 year (p < 0.008). According to this cutoff, men were divided into two groups: BCR detected within 1 year and after a 1-year period. Ten-year CPFS was 49.8% in men with early BCR vs. 81.1% in men with late BCR; CSS was 70.9 vs. 92.8% (p = 0.001). Multivariable analysis confirmed that time until BCR within 1 year predicts CP (p = 0.005) and CRD (p = 0.03).Conclusions: Early BCR is associated with poorer oncological outcomes. The presented results may help both to improve follow-up strategy and opt for more aggressive multimodal treatment of HRPCa in men with very early BCR.

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Section: Discussionsupporting

confidence: 93%

“…It should be mentioned that Briganti et al defined early BCR as that which occurred in the first 3 years after RP. Pompe et al (37) demonstrated that CRD correlates with early BCR (≤1 year), pathological GS, and short PSA-DT. We did not calculate PSA-DT and pathological GS was not a significant factor for CRD in our study.…”

Section: Discussionmentioning

confidence: 99%

Significance of Time Until PSA Recurrence After Radical Prostatectomy Without Neo- or Adjuvant Treatment to Clinical Progression and Cancer-Related Death in High-Risk Prostate Cancer Patients

2019

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“…After primary curative-intent treatment for prostate cancer (PCa) with radical prostatectomy (RP) or radiotherapy, approximately one out of four men experience biochemical recurrence (BCR) (1).…”

Section: Introductionmentioning

confidence: 99%

PSMA PET Validates Higher Rates of Metastatic Disease for European Association of Urology Biochemical Recurrence Risk Groups: An International Multicenter Study

et al. 2021

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The European Association of Urology (EAU) Prostate Cancer Guidelines Panel recommends risk groups for biochemically recurrent prostate cancer (BCR) to identify men at high risk of progression or metastatic disease. The rapidly growing availability of PSMA-directed PET imaging (PSMA PET) will impact prostate cancer staging. We determined the rates of local and metastatic disease in recurrent and persistent prostate cancer stratified by EAU BCR risk groups and biochemical persistence (BCP). Methods:Patients with BCR/BCP were enrolled under the same prospective clinical trial protocol conducted at three sites (n=1777, 91%; UCLA n=662, NCT02940262; UCSF n=508, NCT03353740; Michigan, n=607, NCT03396874); 183 patients with BCP from Universities of Essen, Bologna, and Munich were included retrospectively. Patients with BCR had to have sufficient data to determine EAU risk score. Multivariate, binomial logistic regression models were applied to assess independent predictors of M1 disease.Results: A total of 1960 patients were included. Post-RP EAU BCR low risk, EAU BCR high risk, and BCP groups yield distant metastatic (M1) detection in 43/176 (24%), 342/931 (37%), and 154/386 (40%) of patients. For post-radiotherapy EAU BCR low risk and EAU BCR high risk groups, M1 detection rate was 113/309 (37%) and 110/158 (70%), respectively. BCP, high risk BCR and higher levels of serum PSA were significantly associated with PSMA PET M1 disease in multivariate regression analysis. PSMA-PET revealed no disease in 25% and locoregional only disease in 33% of patients with post-RP or postradiotherapy EAU BCR high risk. Conclusion: Our findings support the new EAU classification; EAU BCR high-risk groups have higher rates of metastatic disease on PSMA PET than the low-risk groups. Discordant subgroups, including metastatic disease in low risk and no disease in high risk patients warrant inclusion of PSMA PET stage to refine risk assessment.

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“…(16) A limitation of the study was the lack of more definitive clinical endpoints such as death and although BCR is a clinically relevant determinate, it is largely considered a "surrogate" endpoint as only a small proportion of BCR patients will develop metastatic disease and/or die of prostate cancer. (2,17) Moreover, though that study did adjust for confounders through multivariable analysis, there was no further survival analysis of competing risks for BCR, such as death from another cause. We are unaware of any other studies which corroborate the work by Skove and we sought to validate these findings in an Australian population by querying the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) registry database.…”

Section: Introductionmentioning

confidence: 99%

Time to Prostate-Specific Antigen Nadir After Radical Prostatectomy – a new potential predictive prognostic parameter and its impact on clinical outcomes

Tran¹,

Moretti²,

O’Callaghan³

2020

Preprint

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BackgroundTo investigate and validate previously published associations between time to prostate-specific antigen nadir and the time-to-nadir after radical prostatectomy with biochemical recurrence and to extend this analysis to overall survival and prostate cancer-specific mortality risk. MethodsThis is a retrospective analysis of 1796 men from the South Australian Prostate Cancer Clinical Outcomes Collaborative database treated with radical prostatectomy between 1998-2018 with available prostate-specific antigen nadir data within 1-6 months after surgery. Uni- and multivariable analyses of prostate-specific antigen nadir, time-to-nadir, biochemical recurrence and death were performed with Cox and competing risks models (adjusted for age, surgery year, tumour features and preoperative prostate-specific antigen).ResultsThe univariable analysis demonstrated those with shorter time-to-nadir <3 months had a decreased risk of biochemical recurrence (log-rank, p=0.0098) compared to those with longer time-to-nadir 3-6 months. For men with a time-to-nadir <3 months, a Log-rank test showed a decreased risk of prostate cancer-specific mortality (p=0.026) compared to time-to-nadir 3-6 months, without a difference in overall survival. Multivariable competing risk analyses indicated that biochemical recurrence was more likely when time-to-nadir was 3-6 months compared to <3 months (sHR=1.43, CI 1.01-2.02, p=0.04).ConclusionsAmong men undergoing radical prostatectomy, a shorter post-operative time-to-nadir <3 months is associated with decreased risk of biochemical recurrence compared to time-to-nadir 3-6 months. Following adjustment for confounders and competing risks, there was no significant difference in time-to-nadir for mortality outcomes.

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Long‐term cancer control outcomes in patients with biochemical recurrence and the impact of time from radical prostatectomy to biochemical recurrence

Abstract: Only a small proportion of BCR patients proceed to MP or PCSM. Besides higher GS and rapid PSA-DT a shorter RP-BCR interval (<12 months) heralds the most aggressive phenotype for progression to all three examined endpoints: MP, PCSM, and OM.

Cited by 29 publications

References 30 publications

Significance of Time Until PSA Recurrence After Radical Prostatectomy Without Neo- or Adjuvant Treatment to Clinical Progression and Cancer-Related Death in High-Risk Prostate Cancer Patients

Significance of Time Until PSA Recurrence After Radical Prostatectomy Without Neo- or Adjuvant Treatment to Clinical Progression and Cancer-Related Death in High-Risk Prostate Cancer Patients

PSMA PET Validates Higher Rates of Metastatic Disease for European Association of Urology Biochemical Recurrence Risk Groups: An International Multicenter Study

Time to Prostate-Specific Antigen Nadir After Radical Prostatectomy – a new potential predictive prognostic parameter and its impact on clinical outcomes

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