Method to determine outcome for patients with prostatic disease

• US 20030235816A1
• Filed: 03/14/2003
• Published: 12/25/2003
• Est. Priority Date: 03/14/2002
• Status: Abandoned Application

• Current Assignee: Baylor College of Medicine (Baylor College), Memorial Sloan-Kettering Cancer Center
• Original Assignee: Baylor College of Medicine (Baylor College)
• Inventors: Kattan, Michael, Scardino, Peter T., Shariat, Shahrokh, Slawin, Kevin M.
• Application Number:
  US10/389,245
• Publication Number:
  US 20030235816A1
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: G01N 33/57434 of prostate

Abstract

A method for prognosis of patients with prostate cancer, e.g., clinically localized prostate cancer, is provided.

Claims

1. A method to determine the risk of progression of a prostate cancer patient after therapy, comprising:

a) detecting or determining the amount or level of VEGF, UPAR, UPA, or sVCAM in a blood sample obtained from a patient prior to therapy for clinically localized prostate cancer; and

b) correlating the amount or level of VEGF, UPAR, UPA, or sVCAM with the risk of progression.

4. The method of claim 1, 2, or 3 wherein the clinical stage of the patient is T3a, T3, T2c, T2b, T2a, T2, T1c, T1b, T1a or T1.

5. The method of claim 1, 2, or 3 wherein the therapy is primary therapy.

6. The method of claim 1, 2, or 3 wherein the therapy is surgery, radical prostatectomy, radiation therapy or a radioactive seed implant.

7. The method of claim 1, 2, or 3 wherein the patient has not been subject to hormonal therapy.

8. The method of claim 1 wherein the amount or level of VEGF is detected or determined with an agent that binds to VEGF.

9. The method of claim 8 wherein the agent is an antibody.

10. The method of claim 9 wherein the agent is detectably labeled or binds to a detectable label.

11. The method of claim 1 wherein the amount of level of sVCAM is detected or determined with an agent that binds sVCAM.

12. The method of claim 11 wherein the agent is an antibody.

13. The method of claim 12 wherein the agent is detectably labeled or binds to a detectable label.

14. The method of claim 1 wherein the amount or level of UPAR is detected or determined with an agent that binds to UPAR.

15. The method of claim 14 wherein the agent is an antibody.

16. The method of claim 15 wherein the agent is detectably labeled or binds to a detectable label.

17. The method of claim 1 wherein the amount or level of UPA is detected or determined with an agent that binds to UPA.

18. The method of claim 17 wherein the agent is an antibody.

19. The method of claim 18 wherein the agent is detectably labeled or binds to a detectable label.

26. The method of claim 1, 2 or 3 wherein the correlating is conducted by a computer.

28. The method of claim 1 wherein the blood sample is a plasma sample.

64. The method of claim 1, 2, 31, 39, 40, 41, 54, 56, 58, 59 or 62 further comprising further correlating one of Gleason score, number of positive cores, number of positive contiguous cores, total cancer length, total cancer in contiguous cores and/or percent tumor involvement from a systemic 12 core biopsy to the risk of progression or non-prostate confined disease.

2. A method to determine the risk of progression of a prostate cancer patient after therapy, comprising:

a) detecting or determining the amount or level of TGF-β

₁ and IL6sR or IL6 in a blood sample, and the Gleason score in a prostate sample, obtained from a patient prior to therapy for clinically localized prostate cancer; and

b) correlating the amount or level of TGF-β

₁ and IL6sR or IL6 and the Gleason score in a prostate sample, with the risk of progression.

20. The method of claim 2 or 3 wherein the amount of level of TGF-β

₁ is detected or determined with an agent that binds TGF-β

₁.

21. The method of claim 20 wherein the agent is an antibody.

22. The method of claim 21 wherein the agent is detectably labeled or binds to a detectable label.

23. The method of claim 2 or 3 wherein the amount of level of IL6sR or IL6 is detected or determined with an agent that binds IL6sR or IL6.

24. The method of claim 23 wherein the agent is an antibody.

25. The method of claim 24 wherein the agent is detectably labeled or binds to a detectable label.

27. The method of claim 2 or 3 wherein the blood plasma sample is a platelet poor plasma sample.

29. The method of claim 2 or 3 further comprising detecting or determining a second Gleason score.

30. The method of claim 2 or 3 further comprising detecting or determining clinical stage.

3. A method to determine the prognosis of a prostate cancer patient after therapy, comprising:

a) detecting or determining the amount or level of TGF-β

₁ and IL6sR or IL6 in a blood sample, and the Gleason score in a prostate sample, obtained from a patient prior to therapy for clinically localized prostate cancer; and

b) correlating the amount or level of TGF-β

₁ and IL6sR or IL6 and the Gleason score in a prostate sample with the risk of non-prostate confined disease.

31. An apparatus, comprising:

a data input means, for input of test information comprising the level or amount of VEGF, UPAR, UPA, or sVCAM, in one or more samples obtained from a mammal;

a processor, executing a software for analysis of the level or amount of VEGF, UPAR, UPA, or sVCAM, in the one or more samples;

wherein the software analyzes the level or amount of VEGF, UPAR, UPA, or sVCAM, in the one or more samples and provides the risk of prostate disease progression in the mammal.

35. The apparatus of claim 31, 32, 33 or 34 wherein the amount or level and score is input manually using the data input means.

36. The apparatus of claim 31, 32, 33 or 34 wherein the software constructs a database of the test information.

65. The apparatus of claim 31, 32, 33, 34, 51, 55, 57, 60 or 63 further comprising correlating one of Gleason score, number of positive cores, number of positive contiguous cores, total cancer length, total cancer in contiguous cores and/or percent tumor involvement from a systemic 12 core biopsy to the risk of progression or non-prostate confined disease.

32. An apparatus, comprising:

a data input means, for input of test information comprising the level or amount of UPAR or UPA in one or more samples obtained from a mammal;

a processor, executing a software for analysis of the level or amount of UPAR or UPA in the one or more samples;

wherein the software analyzes the level or amount of UPAR or UPA in one or more samples and provides the risk of non-prostate confined disease in the mammal.

33. An apparatus, comprising:

a data input means, for input of test information comprising the level or amount of TGF-β

₁ and IL6sR or IL6, and the Gleason score, in one or more samples obtained from a mammal;

a processor, executing a software for analysis of the level or amount of TGF-β

₁ and IL6sR or IL6, and the Gleason score, in the one or more samples;

wherein the software analyzes the level or amount of TGF-β

₁ and IL6sR or IL6, and the Gleason score, in the one or more samples and provides the risk of prostate disease progression in the mammal.

37. The apparatus of claim 33 or 34 wherein the information further comprises a second Gleason score.

38. The apparatus of claim 33 or 34 wherein the information further comprises clinical grade.

34. An apparatus, comprising:

a data input means, for input of test information comprising the level or amount of TGF-β

₁ and IL6sR or IL6, and the Gleason score, in one or more samples obtained from a mammal;

a processor, executing a software for analysis of the level or amount of TGF-β

₁ and IL6sR or IL6, and the Gleason score, in the one or more samples;

wherein the software analyzes the level or amount of TGF-β

₁ and IL6sR or IL6, and the Gleason score, in one or more samples and provides the risk of non-prostate confined disease in the mammal.

39. A method to determine the prognosis of a prostate cancer patient after therapy, comprising:

a) inputting test information to a data input means, wherein the information comprises the level or amount of VEGF, UPAR, UPA, or sVCAM, in one or more samples obtained from a prostate cancer patient;

b) executing a software for analysis of the test information; and

c) analyzing the test information so as to provide the risk of disease progression or non-prostate confined disease in the patient.

40. A method to determine the prognosis of a prostate cancer patient after therapy, comprising:

a) inputting test information to a data input means, wherein the information comprises the level or amount of TGF-β

₁ and IL6sR or IL6, and the Gleason score, in one or more samples obtained from a prostate cancer patient;

b) executing a software for analysis of the test information; and

c) analyzing the test information so as to provide the risk of disease progression or non-prostate confined disease in the patient.

41. A method for predicting a probability of recurrence of prostatic cancer in a patient following radical prostatectomy, comprising:

a) correlating a set of pre-operative factors for the patient to a functional representation of a set of pre-operative factors determined for each of a plurality of persons previously diagnosed with prostatic cancer and having been treated by radical prostatectomy, so as to yield a value for total points for the patient, which set of factors for each of a plurality of persons is correlated with the incidence of recurrence of prostatic cancer for each person in the plurality of persons, wherein the set of pre-operative factors comprises pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade, wherein the functional representation comprises a scale for each of pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally a scale for one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade, a points scale, a total points scale, and a predictor scale, wherein the scales for pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade, each have values on the scales which can be correlated with values on the points scale, and wherein the total points scale has values which may be correlated with values on the predictor scale; and

b) correlating the value on the total points scale for the patient with a value on the predictor scale to predict the quantitative probability of recurrence of prostatic cancer in the patient following radical prostatectomy.

42. The method of claim 41 wherein the functional representation is a nomogram.

43. The method of claim 42 wherein the nomogram is generated with a Cox proportional hazards regression model.

44. The method of claim 41 wherein the patient is a presurgical candidate.

45. The method of claim 41 wherein the probability of recurrence of prostatic cancer is a probability of remaining free of prostatic cancer five years following radical prostatectomy.

46. The method of claim 41 wherein a recurrence of prostatic cancer is characterized as an increased serum PSA level.

47. The method of claim 46 wherein the increased serum PSA level is greater than or equal to 0.2 ng/mL.

48. The method of claim 41 wherein a recurrence of prostatic cancer is characterized as a positive biopsy, bone scan or the application of further treatment for prostate cancer because of the high probability of subsequent recurrence of the cancer.

49. The method of claim 41 wherein the plurality of persons comprises persons with clinically localized prostate cancer not treated previously by radiotherapy, hormone therapy or cryotherapy, and subsequently undergoing radical prostatectomy.

50. The method of claim 41 wherein the set of pre-operative factors further comprise clinical stage, pre-treatment VEGF level, pre-treatment sVCAM level, pre-treatment UPAR level, or pre-treatment UPA level.

51. An apparatus for predicting a probability of disease recurrence in a patient with prostatic cancer following a radical prostatectomy, which apparatus comprises:

a) a correlation of a set of pre-operative factors for each of a plurality of persons previously diagnosed with prostatic cancer and having been treated by radical prostatectomy with the incidence of recurrence of prostatic cancer for each person of the plurality of persons, wherein the set of pre-operative factors comprises pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade; and

b) a means for comparing an identical set of pre-operative factors determined from a patient diagnosed as having prostatic cancer to the correlation to predict the quantitative probability of recurrence of prostatic cancer in the patient following radical prostatectomy.

52. A nomogram for the graphic representation of a quantitative probability that a patient with prostate cancer will remain free of disease following radical prostatectomy, comprising:

a plurality of scales and a solid support, the plurality of scales being disposed on the support and comprising a scale for each of pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade, a points scale, a total points scale and a predictor scale, wherein the scales for pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally the scales for one or more of the pre-treatment PSA level, primary Gleason grade or secondary Gleason grade each has values on the scales, and wherein the scales for pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally the scales for one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade are disposed on the solid support with respect to the points scale so that each of the values on the pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally the one or more of the pre-treatment PSA level, primary Gleason grade or secondary Gleason grade can be correlated with values on the points scale, wherein the total points scale has values on the total points scale, and wherein the total points scale is disposed on the solid support with respect to the predictor scale so that the values on the total points scale may be correlated with values on the predictor scale, such that the values on the points scale correlating with the patient'"'"'s pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade can be added together to yield a total points value, and the total points value can be correlated with the predictor scale to predict the quantitative probability of recurrence.

53. The nomogram of claim 52 wherein the solid support is a laminated card.

54. A method to predict a pre-operative prognosis in a patient comprising:

determining a set of pre-operative factors for a patient, which set comprises pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade;

matching the pre-operative factors to the values on the scales of the nomogram of claim 52;

determining a separate point value for each of the pre-operative factors;

adding the separate point values together to yield a total points value; and

correlating the total points value with a value on the predictor scale of the nomogram to determine the pre-operative prognosis of the patient.

66. The nomogram of claim 52 or 61 further comprising correlating one of Gleason score, number of positive cores, number of positive contiguous cores, total cancer length, total cancer in contiguous cores and/or percent tumor involvement from a systemic 12 core biopsy to the risk of progression or non-prostate confined disease from a systemic 12 core biopsy to predict the quantitative probability of recurrence.

55. An apparatus for predicting a probability of disease recurrence in a patient with prostatic cancer following a radical prostatectomy, which apparatus comprises:

a scale for each of pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade, a points scale, a total points scale and a predictor scale, wherein the scales for pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally the scales for one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade each has values on the scales, and wherein the scales for pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally the scales for one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade are disposed so that each of the values on the pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally the one or more of the pre-treatment PSA level, primary Gleason grade or secondary Gleason grade, can be correlated with values on the points scale, wherein the total points scale has values on the total points scale, and wherein the total points scale is disposed on the solid support with respect to the predictor scale so that the values on the total points scale may be correlated with values on the predictor scale, such that the values on the points scale correlating with the patient'"'"'s pre-treatment TGF-β

₁ level, pre-treatment IL6sR or IL6 level, and optionally one or more of pre-treatment PSA level, primary Gleason grade or secondary Gleason grade can be added together to yield a total points value, and the total points value can be correlated with the predictor scale to predict the quantitative probability of recurrence.

56. A method to determine the risk of progression of a prostate cancer patient after therapy, comprising:

a) providing i) the amount or level of TGF-β

₁ in a blood plasma sample obtained from the patient after therapy;

ii) pathological Gleason score; and

iii) and optionally the amount or level of one or more of IL6sR, IL6 or PSA in a blood sample obtained from the patient prior to therapy; and

b) correlating the amount or level of post-treatment TGF-β

₁, pathological Gleason score and optionally the amount or level of one or more of pre-treatment IL6sR, IL6 or PSA, with the risk of progression.

57. An apparatus, comprising:

a data input means, for input of test information comprising the level or amount of post-treatment TGF-β

₁, pathological Gleason score, and optionally level or amount of one or more of pre-treatment IL6sR, IL6 or PSA, in one or more samples obtained from a mammal;

a processor, executing a software for analysis of the level or amount of post-treatment TGF-β

₁, pathological Gleason score, and optionally level or amount of one or more of pre-treatment IL6sR, IL6 or PSA in the one or more samples;

wherein the software analyzes the level or amount of post-treatment TGF-β

₁, pathological Gleason score, and optionally level or amount of one or more of pre-treatment IL6sR, IL6 or PSA in the one or more samples and provides the risk of prostate disease progression in the mammal.

58. A method to determine the prognosis of a prostate cancer patient after therapy, comprising:

a) inputting test information to a data input means, wherein the information comprises the level or amount of post-treatment TGF-β

₁, pathological Gleason score, and optionally level or amount of one or more of pre-treatment IL6sR, IL6 or PSA, samples obtained from a prostate cancer patient;

b) executing a software for analysis of the test information; and

c) analyzing the test information so as to provide the risk of disease progression or non-prostate confined disease in the patient.

59. A method for predicting a probability of recurrence of prostatic cancer in a patient following radical prostatectomy, comprising:

a) correlating a set of factors for the patient to a functional representation of a set of factors determined for each of a plurality of persons previously diagnosed with prostatic cancer and having been treated by radical prostatectomy so as to yield a value for total points for the patient, which set of factors for each of a plurality of persons is correlated with the incidence of recurrence of prostatic cancer for each person in the plurality of persons, wherein the set of factors comprises post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, wherein the functional representation comprises a scale for each of post-treatment TGF-β

₁ level, pathological Gleason score, and optionally one or more of pre-treatment IL6sR or IL6 or PSA level, a points scale, a total points scale, and a predictor scale, wherein the scales for post-treatment TGF-β

₁ level, pathological Gleason score, and optionally one or more of pre-treatment IL6sR, IL6 or PSA level each have values on the scales which can be correlated with values on the points scale, and wherein the total points scale has values which may be correlated with values on the predictor scale; and

b) correlating the value on the total points scale for the patient with a value on the predictor scale to predict the quantitative probability of recurrence of prostatic cancer in the patient following radical prostatectomy.

60. An apparatus for predicting a probability of disease recurrence in a patient with prostatic cancer following a radical prostatectomy, which apparatus comprises:

a) a correlation of a set of factors for each of a plurality of persons previously diagnosed with prostatic cancer and having been treated by radical prostatectomy with the incidence of recurrence of prostatic cancer for each person of the plurality of persons, wherein the set of factors comprises post-treatment TGF-β

₁ level, pathological Gleason, and optionally one or more of pre-treatment IL6sR, IL6 or PSA level; and

b) a means for comparing an identical set of factors determined from a patient diagnosed as having prostatic cancer to the correlation to predict the quantitative probability of recurrence of prostatic cancer in the patient following radical prostatectomy.

61. A nomogram for the graphic representation of a quantitative probability that a patient with prostate cancer will remain free of disease following radical prostatectomy, comprising:

a plurality of scales and a solid support, the plurality of scales being disposed on the support and comprising a scale for each of post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, a points scale, a total points scale and a predictor scale, wherein the scales for post-treatment TGF-β

₁ level, pathological Gleason score, and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, each has values on the scales, and wherein the scales for post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level are disposed on the solid support with respect to the points scale so that each of the values on the post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level can be correlated with values on the points scale, wherein the total points scale has values on the total points scale, and wherein the total points scale is disposed on the solid support with respect to the predictor scale so that the values on the total points scale may be correlated with values on the predictor scale, such that the values on the points scale correlating with the patient'"'"'s post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, can be added together to yield a total points value, and the total points value can be correlated with the predictor scale to predict the quantitative probability of recurrence.

62. A method to predict a post-operative prognosis in a patient comprising:

determining a set of factors for a patient which set comprises post-treatment TGF-β

₁ level, Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, matching the pre-operative factors to the values on the scales of the nomogram of claim 61;

determining a separate point value for each of the factors;

adding the separate point values together to yield a total points value; and

correlating the total points value with a value on the predictor scale of the nomogram to determine the post-operative prognosis of the patient.

63. An apparatus for predicting a probability of disease recurrence in a patient with prostatic cancer following a radical prostatectomy, which apparatus comprises:

a scale for each of post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, a points scale, a total points scale and a predictor scale, wherein the scales for post-treatment TGF-β

₁ level, pathological Gleason score, and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, each has values on the scales, and wherein the scales for post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level are disposed with respect to the points scale so that each of the values on the post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level can be correlated with values on the points scale, wherein the total points scale has values on the total points scale, and wherein the total points scale is disposed with respect to the predictor scale so that the values on the total points scale may be correlated with values on the predictor scale, such that the values on the points scale correlating with the patient'"'"'s post-treatment TGF-β

₁ level, pathological Gleason score and optionally one or more of pre-treatment IL6sR, IL6 or PSA level, can be added together to yield a total points value, and the total points value can be correlated with the predictor scale to predict the quantitative probability of recurrence.

67. A method to determine the risk of progression of a prostate cancer patient after therapy, comprising:

a) providing i) the amount or level of TGF-β

₁ in a blood plasma sample obtained from a patient prior to therapy;

ii) the amount or level of IL6sR or IL6 in a blood sample obtained from a patient prior to therapy; and

iii) the Gleason score in a prostate sample; and

b) correlating the amount or level of TGF-β

₁ and IL6sR or IL6 and the Gleason score in a prostate sample with the risk of non-prostate confined disease.