Investigative clinical study on prostate cancer: on the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients

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Objectives: Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. Patients and Methods: The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≧7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≧7) prostate cancer. Results: Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable (FT) were always highly significant for patients with (1) intraprostate and extraprostate disease, and (2) low-grade and high-grade prostate cancer. Conclusions: According to the prognostic PSA/FT ratio, significantly lower levels of FT are detected in prostate cancer patients with extensive and high-grade disease. Also, significant linear correlations of FT predicting PSA are assessed in the different groups and subgroups of patients clustered according to the prognostic PSA/FT ratio. Confirmatory studies are needed.

Section: Introductionmentioning

confidence: 68%

Investigative Clinical Study on Prostate Cancer Part III: Exploring Total PSA and Free Testosterone Distributions and Linear Correlations in Groups and Subgroups of Operated Prostate Cancer Patients according to the Total PSA/FT Ratio

Porcaro¹,

Petrozziello²,

Romano

et al. 2010

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“…The main elementary difference was the androgen investigated (FT) and the approach to the ratio (total PSA/FT ratio). This approach was the result of the methodology for which the study was planned, as we reported in the first paper [24] . In the present study, we tried to explore the PSA/FT ratio as a marker for assessing pT and pGS.…”

Section: Discussionmentioning

confidence: 99%

“…In a preceding paper [24] , we showed that prostate cancer biology is related to serum levels of both free testosterone (FT) and PSA, the former as the stimulating growth factor and the latter as the product of cancer activity. We also demonstrated that PSA levels were linearly related to FT and that the PSA/FT ratio could be considered as a marker expressing different cancer phenotype biologies.…”

Section: Introductionmentioning

confidence: 99%

Investigative Clinical Study on Prostate Cancer Part II: On the Role of the Pretreatment Total PSA to Free Testosterone Ratio as a Marker Assessing Prostate Cancer Prognostic Groups after Radical Retropubic Prostatectomy

Porcaro¹,

Monaco²,

Romano

et al. 2010

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Objectives: To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. Patients and Methods: 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. Results: The average age was 65.80 (range 51.21–77.26) years, mean PSA was 8.88 (range 1.22–44.27) µg/l, mean FT was 35.32 (range 13.70–69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04–1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≧0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). Conclusions: Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and pGS.

“…In the first 3 papers of our study we have shown that (a) ft was a significant predictor of total PSA [30] , (b) the PSA/ft ratio was a significant parameter in clustering prognostic groups [31] , and (c) significantly lower levels of ft were detected when clustering the patient population in prognostic groups according to the PSA/ft ratio [Porcaro et al, paper under review]. In the present study, we have confirmed that tt was a significant predictor of ft [29] , but we have also shown that the ft/tt ratio was a significant parameter in clustering the patient population, a result never reported in the literature.…”

Section: Discussionmentioning

confidence: 59%

“…= coefficient (b0 = intercept, b1 = slope coefficient). Our present and former results [30,31] might provide interesting and practical models for studying prostate cancer biology. As already known, prostate cancer is androgen-dependent [1] and PSA production and secretion is dependent on androgenic stimulation at the cellular level [4,6] .…”

Section: Discussionmentioning

confidence: 61%

Investigative Clinical Study on Prostate Cancer Part IV: Exploring Functional Relationships of Total Testosterone Predicting Free Testosterone and Total Prostate-Specific Antigen in Operated Prostate Cancer Patients

Porcaro

Petrozziello²,

Migliorini³

et al. 2011

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Objectives: To explore, in operated prostate cancer patients, functional relationships of total testosterone (tt) predicting free testosterone (ft) and total PSA. Patients and Methods: 128 operated prostate cancer patients were simultaneously investigated for tt, ft and PSA before surgery. Patients were not receiving 5α-reductase inihibitors, LH-releasing hormone analogues and testosterone replacement treatment. Scatter plots including ft and PSA versus tt were computed in order to assess the functional relationship of the variables. Linear regression analysis of tt predicting ft and PSA was computed. Results: tt was a significant predictor of the response variable (ft) and different subsets of the patient population were assessed according to the ft to tt ratio. PSA was related to tt according to a nonlinear law. tt was a significant predictor of PSA according to an inversely nonlinear law and different significant clusters of the patient population were assessed according to the different constant of proportionality computed from experimental data. Conclusions: In our prostate cancer population, ft was significantly predicted by tt according to a linear law, and the ft/tt ratio was a significant parameter for assessing the different clusters. Also, tt was a significant variable predicting PSA by a nonlinear law and different clusters of the patient population were assessed by the different constants of proportionality. As a theory, we explain the nonlinear relation of tt in predicting PSA as follows: (a) the number of androgen-independent prostate cancer cells increases as tumor volume and PSA serum levels rise, (b) the prevalence of androgen-independent cells producing a substance which inhibits serum LH, and (c) as a result lower levels of serum tt are detected.