Compositions and methods for active surveillance of prostate cancer

Abstract

Aspects of the disclosure relate to improved methods and systems for active surveillance of subject having non-aggressive prostate cancer.

1 . A method of evaluating a subject previously diagnosed as having non-aggressive prostate cancer, the method comprising:
 i) subjecting a blood sample of the subject to one or more immunoassays that measure levels of one or more kallikrein markers selected from: free prostate specific antigen (fPSA), intact prostate specific antigen (iPSA), total prostate specific antigen (tPSA) and human kallikrein 2 (hK2); and   ii) determining the probability that a prostate tissue biopsy obtained from the subject would contain detectable aggressive prostate cancer by weighting the measured one or more kallikrein marker levels and at least one clinical factor.   
     
     
         2 . The method of  claim 1 , wherein if the probability that the prostate tissue biopsy obtained from the subject would contain detectable aggressive prostate cancer is above a threshold level, a follow-up prostate tissue biopsy is obtained from the subject and analyzed to further evaluate presence of aggressive prostate cancer. 
     
     
         3 . The method of  claim 1 , wherein the non-aggressive prostate-cancer is associated with a Gleason score of 6. 
     
     
         4 . The method of  claim 1 , wherein the aggressive prostate cancer is associated with a Gleason score of 7 or more. 
     
     
         5 . The method of  claim 1 , wherein the blood sample is obtained from the subject within 6 months to 12 months from an initial diagnosis of non-aggressive prostate cancer. 
     
     
         6 . The method of  claim 1  further comprising repeating steps i) and ii) at least once. 
     
     
         7 . The method of  claim 3  further comprising repeating steps i) and ii) at least once within 6 months to 12 months from first performing steps i) and ii). 
     
     
         8 . The method of  claim 1  further comprising repeating steps i) and ii) at least twice, wherein the interval between each set of steps i) and ii) is in a range of 6 months to 1 year. 
     
     
         9 . The method of  claim 1  further comprising repeating steps i) and ii) at least once per year for up to five years. 
     
     
         10 . The method of  claim 1 , wherein the at least one clinical factor is the subject's age. 
     
     
         11 . The method of  claim 1 , wherein the at least one clinical factor is a parameter indicative of the outcome of a digital rectal examination performed on the subject. 
     
     
         12 . The method of  claim 1 , wherein the at least one clinical factor is selected from: number of prostate tissue biopsies performed on the subject to date; results of prior prostate tissue biopsies performed on the subject to date; occurrence of any negative biopsy since an initial diagnosis of non-aggressive prostate cancer; occurrence of any negative biopsy in one-year prior to obtaining the blood sample; total number of biopsies since an initial diagnosis of non-aggressive prostate cancer; prostate volume on prior biopsy; number of positive cores on prior biopsy; percent positive cores on prior biopsy; cross-sectional area of cancer in biopsy core sections; maximum cross-sectional area of cancer in any biopsy core sections; PSA density; race of subject; family history of prostate cancer; maximum percent of positive cores from any prior biopsy; and maximum number of positive cores from any prior biopsy. 
     
     
         13 . The method of  claim 1 , wherein the probability that a subject has aggressive prostate cancer is further determined by weighting a cubic spline term based on the measured kallikrein marker level(s). 
     
     
         14 . A method for determining a probability of an event associated with prostate cancer, the method comprising:
 receiving, via an input interface, information indicative of levels of one or more kallikrein markers selected from: tPSA, fPSA, iPSA, and hK2 in a blood plasma sample of a subject previously diagnosed as having a non-aggressive prostate cancer;   receiving, via an input interface, information about at least one clinical factor of the subject   evaluating, using at least one processor, a logistic regression model based, at least in part, on the received information to determine a probability of an event associated with prostate cancer in the subject, wherein evaluating the logistic regression model comprises:   determining the probability of the event associated with prostate cancer based, at least in part, on the information indicative of levels of one or more of tPSA, fPSA, iPSA, and hK2 and the information about the at least one clinical factor; and   outputting an indication of the probability of the event associated with prostate cancer, wherein the event associated with prostate cancer is an upgrade from a non-aggressive prostate cancer to an aggressive prostate cancer.   
     
     
         15 . A computer for determining a probability of an event associated with prostate cancer, the computer comprising:
 an input interface configured to receive information indicative of levels of one or more kallikrein markers selected from: tPSA, fPSA, iPSA, and hK2 in a blood plasma sample of a subject and information about at least one clinical factor of the subject;   at least one processor programmed to evaluate a logistic regression model based, at least in part, on the received information to determine a probability of an event associated with prostate cancer in the subject, wherein evaluating the logistic regression model comprises:   determining the probability of the event associated with prostate cancer based, at least in part, on the information indicative of levels of one or more of tPSA, fPSA, iPSA, and hK2 and the information about the at least one clinical factor; and   an output interface configured to output an indication of the probability of the event associated with prostate cancer, wherein the event associated with prostate cancer is an upgrade from a non-aggressive prostate cancer to an aggressive prostate cancer.   
     
     
         16 . A system for determining a probability of an event associated with prostate cancer, the system comprising:
 a) a detector configured to measure levels of one or more kallikrein markers selected from: tPSA, fPSA, iPSA, and hK2 in a blood plasma sample of a subject; and   b) a computer in electronic communication with the detector, wherein the computer comprises:   i) an input interface configured to receive information from the detector indicative of the measured levels of one or more of tPSA, fPSA, iPSA, and hK2, and to receive information about at least one clinical factor of the subject;   ii) at least one processor programmed to evaluate a logistic regression model based, at least in part, on the received information to determine a probability of an event associated with prostate cancer in the subject, wherein evaluating the logistic regression model comprises:   determining the probability of the event associated with prostate cancer based, at least in part, on the information indicative of levels of one or more of tPSA, fPSA, iPSA, and hK2 and the information about the at least one clinical factor; and   iii) an output interface configured to output an indication of the probability of the event associated with prostate cancer, wherein the event associated with prostate cancer is an upgrade from a non-aggressive prostate cancer to an aggressive prostate cancer.   
     
     
         17 . A computer-readable storage medium encoded with a plurality of instructions that, when executed by a computer, perform a method for determining a probability of an event associated with prostate cancer, wherein the method comprises:
 evaluating a logistic regression model based, at least in part, on information indicative of levels of one or more kallikrein marker selected from: tPSA, fPSA, iPSA, and hK2 in a blood plasma sample of a subject and information about at least one clinical factor of the subject to determine a probability of an event associated with prostate cancer in the subject, wherein evaluating the logistic regression model comprises:   determining the probability of the event associated with prostate cancer based, at least in part, on the information indicative of levels of one or more of tPSA, fPSA, iPSA, and hK2 and the at least one clinical factor; and   outputting an indication of the probability of the event associated with prostate cancer is an upgrade from a non-aggressive prostate cancer to an aggressive prostate cancer.   
     
     
         18 . The method of  claim 14 , wherein the at least one clinical factor is the subject's age. 
     
     
         19 . The method of  claim 14 , wherein the at least one clinical factor is a parameter indicative of the outcome of a digital rectal examination performed on the subject. 
     
     
         20 . The method of  claim 14 , wherein the at least one clinical factor is selected from: number of prostate tissue biopsies performed on the subject to date; results of prior prostate tissue biopsies performed on the subject to date; occurrence of any negative biopsy since an initial diagnosis of non-aggressive prostate cancer; occurrence of any negative biopsy in one-year prior to obtaining the blood sample; total number of biopsies since an initial diagnosis of non-aggressive prostate cancer; prostate volume on prior biopsy; number of positive cores on prior biopsy; percent positive cores on prior biopsy; cross-sectional area of cancer in biopsy core sections; maximum cross-sectional area of cancer in any biopsy core sections; PSA density; race of subject; family history of prostate cancer; maximum percent of positive cores from any prior biopsy; and maximum number of positive cores from any prior biopsy.