title: 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.
abstract: OBJECTIVE
  To show that prostate cancer biology is related to serum levels of both free testosterone (FT) and prostate-specific antigen (PSA), that PSA level is linearly related to FT and that the PSA to FT ratio may be considered as the growth rate parameter expressing cancer phenotype biology.
  
  
  METHODS
  The study includes 135 consecutive patients diagnosed with prostate cancer. Pretreatment simultaneous serum samples for analyzing total testosterone (TT), FT and total PSA levels were obtained. The study was assessed according to a multidimensional approach of the five continuous variables including TT, FT, PSA, AGE and percentage of positive biopsies (=P+). The all sets of data were considered as one--sample with no groupings among the observations. Multivariate analysis included factor analysis (FA) and principal component analysis (PCA). Multivariate inferential statistics for comparing different groups of patients according to the PSA to free testosterone ratio (PSA/FT) included Hotteling's multivariate two-sample T²-Test for comparing two mean vectors as well as Box's M-Test with the chi-square approximation for comparing multiple covariance matrices when patients were sampled in more than two groups.
  
  
  RESULTS
  Factor analysis showed the two natural grouping of variables, FT-TT and PSA-P+. PCA assessed FT and PSA as the two variables with large variances having a notable influence on the first two principal components. Multiple linear regression analysis showed that all the income variables, except age, significantly predicted the PSA/FT ratio. Patients were first sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20) and group 2 (PSA/FT > 0.20), and Hotteling's multivariate two sample T²-Test was significant (P < 0.01). Patients were then sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20), group 2 (PSA/FT > 0.20 and ≤ 0.40), and group 3 (PSA/FT > 0.40), and Box's M-Test comparing the covariance matrices of the 3 groups differed significantly (P < 0.001). Finally, patients were sampled according to the PSA/FT ratio in 6 groups, and Box's M-Test was again significant (P < 0.001).
  
  
  CONCLUSIONS
  The PSA to FT ratio is the growing rate parameter expressing different biology patterns and assessing different groups of prostate cancer patients. In our opinion, the results of the present study might have wide applications in understanding, assessing and planning prostate cancer studies including basic science, screening, assessing risk of the disease, predicting disease stage as well natural history after a planned treatment involving biochemical recurrence, progression, hormone refractory prostate cancer and disease-specific survival.
authors.affiliation: Department of Urology, Azienda Ospedaliera, Universitaria di Verona, Ospedale Civile Maggiore, Verona, Italy. drporcaro@yahoo.com
authors.forename: Antonio B
authors.initials: AB
authors.lastname: Porcaro
authors.forename: Filippo
authors.initials: F
authors.lastname: Migliorini
authors.forename: Mario
authors.initials: M
authors.lastname: Romano
authors.forename: Aldo
authors.initials: A
authors.lastname: Petrozziello
authors.forename: Stefano Zecchini
authors.initials: SZ
authors.lastname: Antoniolli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Rubilotta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lacola
authors.forename: Teodoro
authors.initials: T
authors.lastname: Sava
authors.forename: Claudio
authors.initials: C
authors.lastname: Ghimenton
authors.forename: Beatrice
authors.initials: B
authors.lastname: Caruso
authors.forename: Carmelo
authors.initials: C
authors.lastname: Monaco
authors.forename: Luigi
authors.initials: L
authors.lastname: Comunale
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D013739:Testosterone / Q000097:blood*
chemical_list: D013739:Testosterone; D017430:Prostate-Specific Antigen