Management of Prostate Cancer Post-Prostatectomy

1. Management of Prostate Cancer Post-Prostatectomy Ajita Narayan, MD, PhD Lafayette Cancer Care

2. To paraphrase Benjamin Disraeli “Lies, more lies and then there is statistics…….”

3. In prostate cancer “Controversy, more controversy and then there are statistics…”

4. Relative power struggle!! Radiation Oncologists Medical Oncologists Urologists

5. Statistics (cancer) • A total of 1,529,560 new cancer cases and 569,490 deaths from cancer are projected to occur in the United States in 2010. Jemal, A., Siegel, R., Xu, J., Ward, E., CA Cancer J Clin 2010;60;277-300; Cancer Statistics, 2010

6. New cases & Death rates 2010 Jemal, A., Siegel, R., Xu, J., Ward, E., CA Cancer J Clin 2010;60;277-300; Cancer Statistics, 2010

8. It is generally accepted that the increase in number of newly diagnosed prostate cancers in US men has resulted from PSA screening that detected many early-stage prostate cancers • Example: percentage of low risk disease has increased from 29.8% (1989-92) to 45.3% (1999-2001); p<0.001

9. Ergo…… • The comparatively low death rate suggests that unless prostate cancer itself is becoming biologically less aggressive, increased public awareness with earlier detection and treatment has begun to affect mortality from this prevalent cancer.

11. The “Manogram”

12. Since we do not have one of those….. • Prostate ca often diagnosed while asymptomatic with a PSA. However, screening with serum PSA is controversial • Either by digital rectal examination (DRE) or due to genitourinary symptoms: • On DRE, asymmetric areas of induration or frank nodules are suggestive of prostate cancer • Urinary urgency, nocturia, frequency, and hesitancy are usually limited to patients with relatively advanced prostate cancer.

15. Pretreatment risk stratification for prostate cancer

16. Serum PSA elevation • PSA is a prostate-specific marker, and elevations can be caused by either prostate cancer or benign conditions such as BPH. • Measure BEFORE biopsy • There is significant overlap in the serum PSA values that accompany prostate cancer and BPH, but the likelihood of finding cancer on a prostate biopsy increases with higher PSA values • Normal intra-individual and intra-assay fluctuations in serum PSA

17. Gleason grade and score • The pathologist assigns a grade to the most common tumor pattern, and a second grade to the next most common tumor pattern. The two grades are added together to get a Gleason score. • For example, if the most common tumor pattern was grade 3, and the next most common tumor pattern was grade 4, the Gleason score would be 3+4 = 7.

18. Gleason Score • The Gleason grade ranges from 1 to 5, with 5 having the worst prognosis. • The Gleason score ranges from 2 to 10, with 10 having the worst prognosis. • For Gleason score 7, a Gleason 4+3 is a more aggressive cancer than a Gleason 3+4.

19. Estimates of Life Expectancy • Key determinant in treatment decision-making • Difficult to extrapolate the rates of life expectancy when calculated for groups of men, to an individual patient • Minnesota Metropolitan Life Insurance Tables or Social Security Administration Life Insurance Table-examples of tables used to calculate life expectancy • Should be modified by overall health

20. Why does it matter? • Rx recommendations could change drastically if referring to prostate cancer in a young man in poor health or an older man in excellent health

21. Normograms can be used to inform treatment decision-making for men contemplating active surveillance, RP, neurovascular bundle preservation, or omission of PLND during RP, brachytherapy or EBRT. • Biochemical PFS can be reassessed post-operatively using age, diagnostic serum PSA and pathologic grade and stage. Kattan, M, Eastham J et al, J Urol 2003 170 (5) 1792-7; Stephenson, A, Scardino P et al., J Natl Cancer Inst 2006 98 (10) 715-717; Graefen, M et al., J Urol 2001 165: 857-863; Ohori M et al., J Urol 2004 171: 1844-1849

22. Partin Tables • Originally developed by urologists Alan W. Partin, M.D., Ph.D., and Patrick C. Walsh, M.D. • Tables combine clinical stage, Gleason grade, preop PSA level to predict pathologic stage: 1. Organ confined 2. Extracapsular (extraprostatic) extension 3. Seminal Vesicle invasion 4. Lymph node mets

25. Treatment optionsT1/T2 disease • The standard approaches for men with organ-confined T1/T2 prostate cancer are • radical prostatectomy (RP) • external beam radiation therapy (EBRT), • brachytherapy, and • active surveillance For patients receiving definitive treatment for T1/T2 prostate cancer, the choice of therapy is largely a matter of patient preference. There is no evidence that the cure rate is different with RP, EBRT, or brachytherapywhen patients are stratified based upon prognostic characteristics

26. Intermediate- or high-risk T1/T2 prostate cancer • For these patients definitive treatment rather than active surveillance • Intermediate-risk disease- EBRT, brachytherapy, or RP • High-risk disease- ADT plus EBRT or RP plus adjuvant EBRT

27. Advantages of main treatment for early prostate cancer: EBRT • Effective long term control with high dose Rx • Low risk of urinary incontinence • Wide range of ages • When combined with hormonal therapy, offers a chance of cure in high-risk of disease • Treatments can eradicate extension of tumor beyond the margins of prostate

28. Advantages of main treatment for early prostate cancer: Brachytherapy • Cancer control rate equal to surgery and EBRT for organ-confined tumor • Quicker than EBRT (one treatment) • Available for cure in a wide range of ages and in those with comorbidities

29. Advantages of main treatment for early prostate cancer: Radical Prostatectomy • Effective long-term cancer control • Prediction of prognosis can be more precise based on pathologic features in specimen • Pelvic lymph node dissection is possible through the same incision • PSA failure easy to predict

30. Advantages of main treatment for early prostate cancer: Active Observation • Reduces overtreatment • Avoids or postpones treatment-associated complications • Has no effect on work or social activities

31. Contraindications to main treatment options for early prostate cancer • RP: High operative risk, ‘medical age’ of 70 or more, neurogenic bladder, morbid fear of surgery • Active observation: High grade tumors, pt preference, expected survival of 10 or more years.

32.  Other Approaches • Include various forms of ablation therapy and systemic hormonal therapy rather than therapy directly to the prostate: • Ablation therapy: • Cryotherapy and high-intensity focused ultrasound (HIFU) have been used to destroy tissue, either by freezing or by generating local thermal energy. These ablation techniques can be applied focally, subtotally, or to the entire prostate gland

33. Primary hormone therapy • Has been used in patients seeking active therapy but wishing to avoid the side effects of RP or RT. • The available evidence suggests that this approach does NOT have a role in patients with clinically localized disease.

34. Benefit of early treatment • Detection of early asymptomatic recurrence following treatment for localized prostate cancer is useful only if it decreases morbidity or mortality. While data directly addressing this issue are lacking, there is some indirect evidence that early detection and treatment of a recurrence can improve outcomes. • Potential benefits and secondary treatment options are dictated by whether recurrence is systemic or local, and whether the initial treatment was surgery or radiation (EBRT or brachytherapy).

35. Post prostatecomy options

36. Post prostatecomy options • Post prostatectomy treatment options varies with the individual patient and needs to be done in a multidisciplinary setting i.e. Medical Oncologist, Radiation Oncologist, Urologist Options include • Post op Surveillance • Radiation therapy • Hormonal therapy • Chemotherapy

37. Follow-up surveillance after treatment for prostate cancer • No widely accepted, evidence-based guidelines that define optimal surveillance for men who have been treated for localized prostate cancer • Potential benefits and secondary treatment options are dictated by whether recurrence is systemic or local, and whether the initial treatment was surgery or radiation (EBRT or brachytherapy).

38. Digital Rectal Exam

39. The lion’s DRE No fuss, no complaints……..

40. If there is recurrence….. • The majority of recurrences following RP or RT for localized prostate cancer are asymptomatic • Digital rectal examination (DRE) • Serum PSA is the mainstay of surveillance testing in men who have undergone therapy for localized prostate cancer • While the use of PSA for cancer screening is controversial, it is an excellent tumor marker in men with an established diagnosis of prostate cancer

41. Definition of PSA recurrence •  Depends upon the initial treatment • All prostate tissue is removed during a successful RP. Thus, any detectable PSA in the serum using the standard immunoassay (typical limit of detection is 0.05 ng/ml) theoretically indicates remaining prostate tissue, and presumably represents persistent or recurrent disease

42. Definition of PSA recurrence • Biochemical failure following RT is more complicated, since there is benign tissue remaining after RT • ASTRO (American society for radiation oncology) guidelines on PSA recurrence were revised in 2005 (Phoenix Criteria)

43. Phoenix criteria  • PSA rise by ≥2 ng/mL above the nadir PSA is considered the standard definition for biochemical failure after external beam RT, regardless of whether or not a patient receives androgen deprivation therapy. • The date of failure is defined by the time the rise in PSA is noted

44. PSA bounce • Serum PSA levels typically fall after RT and can then rise ("bounce") transiently, at a median of 12 to 18 months after treatment. • Can occur in the absence of recurrent disease and does not necessarily constitute an indication for therapeutic intervention.

45. American Urological Association Best Practice Policy regarding the use of PSA in the post treatment management of prostate cancer

46. Follow-up strategy after radical prostatectomy based on pathologic grade and stage • All men: post-prostatectomy baseline PSA at 3 months, then as follows:

47.  Bone scan remains a sensitive and reliable test for detecting the presence of skeletal metastases: But role for early detection of asymptomatic recurrence has been largely supplanted by serial PSA testing • No role for transrectal ultrasound (TRUS) of the prostate or prostatic fossa as a screening test for recurrence of localized prostate cancer • Routine pelvic CT scans are not indicated because of the limited sensitivity of CT to detect low volume recurrent disease

48. The ProstaScint scan is a radiolabeled monoclonal antibody imaging test that is approved in the United States as an aid to determining the site of recurrence (local versus distant) in men with a PSA-only recurrence after RP • National Comprehensive Cancer Network (NCCN) recommend PSA testing every 6 mths for the first 5 years, then annual testing thereafter. The NCCN also recommends annual DRE.

49. Adjuvant RT vs. Postop surveillance • Adj RT decreases the risk of biochemical relapse, but it requires administering RT to some patients who would otherwise never require treatment. • Postoperative surveillance without treatment followed by salvage RT at the first evidence of a rising serum PSA entails the risk that distant metastases might develop in some men who would have been rendered disease-free with immediate adjuvant treatment

50. Adjuvant RT • Extended follow-up from large clinical trials provides evidence that adjuvant RT • is well tolerated • it improves the biochemical and local control rates in men who are found to have pT3 disease or diffusely positive resection margins at RP • improves metastasis-free and overall survival