Total and free PSA kinetics in patients without prostate cancer undergoing radical cystoprostatectomy

Gregorakis, Alkibiades; Stefanakis, S.; Malovrouvas, Dimitrios; Petraki, Konstantina; Gourgiotis, Dimitrios; Scorilas, Andreas

doi:10.1002/pros.20733

Cited by 6 publications

(5 citation statements)

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“…A linear one-compartment model ( Figure 1 ) was used to describe the pharmacokinetics of a protein serum tumor biomarker in blood, including tumor biomarker secretion by tumor cells (and healthy cells, if background biomarker secretion is also present), transfer to the intravascular space, and final degradation and/or removal from the plasma (represented as outflow [ F out ] in the model). By priming the model parameters on the basis of the literature data for two established and well-studied tumor biomarkers, CA125 for ovarian cancer and PSA for prostate cancer, the potential detection limits needed for a proteomic blood test with regards to tumor burden were calculated under varying physiological and assay conditions ( Tables 1 – 4 ) [ 6 – 8 , 14 , 20 – 24 , 26 , 28 – 31 ]. A sensitivity analysis of the model (by varying model parameters over a range of parameter assumptions) resulted in a wide range of minimally detectable tumor sizes depending on the specific chosen conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The reported sensitivities for clinically available PSA immunoassays range between detection limits of 0.01 ng/ml and 0.1 ng/ml [ 14 , 23 , 24 ]. As mentioned before, the cut-off level for the distinction between healthy and disease depends on whether the blood biomarker is secreted by normal cells or by tumor cells only.…”

Section: Methodsmentioning

confidence: 99%

“…Prostate cancer has a high prevalence in detectable preclinical stages. The introduction of the blood biomarker prostate-specific antigen (PSA) for screening of prostate cancer has already caused a “stage migration” [ 14 ]. The introduction of screening for prostate cancer using PSA and digital rectal examination has resulted in increased detection of prostate cancer in early stages when the disease is still curable.…”

Section: Introductionmentioning

confidence: 99%

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Cancer Screening: A Mathematical Model Relating Secreted Blood Biomarker Levels to Tumor Sizes

et al. 2008

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BackgroundIncreasing efforts and financial resources are being invested in early cancer detection research. Blood assays detecting tumor biomarkers promise noninvasive and financially reasonable screening for early cancer with high potential of positive impact on patients' survival and quality of life. For novel tumor biomarkers, the actual tumor detection limits are usually unknown and there have been no studies exploring the tumor burden detection limits of blood tumor biomarkers using mathematical models. Therefore, the purpose of this study was to develop a mathematical model relating blood biomarker levels to tumor burden.Methods and FindingsUsing a linear one-compartment model, the steady state between tumor biomarker secretion into and removal out of the intravascular space was calculated. Two conditions were assumed: (1) the compartment (plasma) is well-mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein that is secreted by tumor cells into the extracellular fluid compartment, and a certain percentage of the secreted protein enters the intravascular space at a continuous rate. The model was applied to two pathophysiologic conditions: tumor biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor cells and healthy normal cells. To test the model, a sensitivity analysis was performed assuming variable conditions of the model parameters. The model parameters were primed on the basis of literature data for two established and well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]). Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor biomarker reaching the plasma, the calculated minimally detectable tumor sizes ranged between 0.11 mm3 and 3,610.14 mm3 for CA125 and between 0.21 mm3 and 131.51 mm3 for PSA. When biomarker secretion by healthy cells and tumor cells was assumed, the calculated tumor sizes leading to positive test results ranged between 116.7 mm3 and 1.52 × 106 mm3 for CA125 and between 27 mm3 and 3.45 × 105 mm3 for PSA. One of the limitations of the study is the absence of quantitative data available in the literature on the secreted tumor biomarker amount per cancer cell in intact whole body animal tumor models or in cancer patients. Additionally, the fraction of secreted tumor biomarkers actually reaching the plasma is unknown. Therefore, we used data from published cell culture experiments to estimate tumor cell biomarker secretion rates and assumed a wide range of secretion rates to account for their potential changes due to field effects of the tumor environment.ConclusionsThis study introduced a linear one-compartment mathematical model that allows estimation of minimal detectable tumor sizes based on blood tumor biomarker assays. Assuming physiological data on CA125 and PSA from the literature, the model predicted detection limits of tumors that were in qualitative agreement with the actual clinical performance of both biomarkers. The model may be helpful in future estimation of minimal detectable ...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cancer Screening: A Mathematical Model Relating Secreted Blood Biomarker Levels to Tumor Sizes

et al. 2008

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“…However, to our knowledge, few studies have focused on the value of Tc‐99m HYNIC PSMA SPECT/CT in patients with BR After RP . Moreover, rapid changes in PSA kinetics are an indicator of poor prognosis after RP or radiation therapy . Therefore, it is possible that Tc‐99m HYNIC PSMA SPECT/CT is more likely to be positive not only in patients with high levels of trigger PSA but also in patients with faster changes in PSA kinetics.…”

Section: Introductionmentioning

confidence: 99%

Relationship between PSA kinetics and Tc‐99m HYNIC PSMA SPECT/CT detection rates of biochemical recurrence in patients with prostate cancer after radical prostatectomy

Liu

Zhu

et al. 2018

The Prostate

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“…Thus, our data suggest that that routine PSA surveillance is unnecessary following complete removal of the prostate if the serum PSA is initially undetectable postoperatively. Gregorakis et al [11] recently reported on the serum PSA elimination kinetics in a small cohort of patients who underwent RCP without prostate cancer. The authors demonstrated a biphasic elimination pattern for PSA, with an initial rapid exponential phase half-life of 4.27 h and a terminal nonexponential phase half-life of 63 h. Accordingly, these data support the confirmation of an undetectable PSA level at 3 months after RCP for patients with benign prostate pathology, after which it appears that PSA monitoring might be discontinued.…”

Section: Discussionmentioning

confidence: 99%

Is Prostate-Specific Antigen Surveillance Necessary in Men with Benign Prostate Pathology following Radical Cystoprostatectomy for Bladder Cancer?

et al. 2010

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Background: Radical cystoprostatectomy (RCP) remains the gold standard for the treatment of muscle-invasive bladder cancer. There are limited data regarding the clinical impact and detection of PSA following complete prostatectomy or the need to monitor serum PSA in patients with benign prostate pathology at time of RCP. The purpose of our study was to analyze the postoperative PSA characteristics of men without prostate cancer who underwent a RCP for bladder cancer. Methods: The demographic, clinical and pathologic data were reviewed on 138 men who underwent RCP for bladder cancer from 1994 to 2008. Patients with known or incidentally discovered prostate cancer on final pathology were excluded from this study, and postoperative serum PSA values were reviewed in the remaining men. Results: The median age of the study population was 64 years (range 40–84). At a mean follow-up of 40.7 months, 137 (99.3%) of patients had an undetectable serum PSA. The one (0.7%) case in which serum PSA was not undetectable underwent an apex-sparing prostatectomy at the time of cystectomy. Conclusions: Serum PSA should remain undetectable for men with benign prostate pathology undergoing complete prostatectomy at the time of RCP. Elevated serum PSA following complete RCP in men with bladder cancer and pathologically confirmed benign prostate findings is rare. If the serum PSA is undetectable 3 months after RCP with benign prostate pathology, there is no need for continued PSA monitoring. These data support the notion that potential nonprostatic sources of PSA are clinically insignificant following complete removal of the prostate.

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Total and free PSA kinetics in patients without prostate cancer undergoing radical cystoprostatectomy

Abstract: Comparing PSA kinetics after radical cystoprostatectomy with those of radical prostatectomy, it appears that PSA follows the same elimination pattern in both models. In contrast, Free PSA and Free/Total Ratio elimination kinetics' patterns differ between the two surgical models.

Cited by 6 publications

References 49 publications

Cancer Screening: A Mathematical Model Relating Secreted Blood Biomarker Levels to Tumor Sizes

Cancer Screening: A Mathematical Model Relating Secreted Blood Biomarker Levels to Tumor Sizes

Relationship between PSA kinetics and Tc‐99m HYNIC PSMA SPECT/CT detection rates of biochemical recurrence in patients with prostate cancer after radical prostatectomy

Is Prostate-Specific Antigen Surveillance Necessary in Men with Benign Prostate Pathology following Radical Cystoprostatectomy for Bladder Cancer?

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