1. Surgical Treatment in Locally Advanced Prostate Cancer
Bertrand Guillonneau
Paris, France

2. Surgical Treatment in Locally Advanced Prostate Cancer
What is/are the definition/s of LAPCa ?
How to diagnose pre-op LAPCa?
What are the rationales for surgery?
What are the surgical quality criteria?
What are the results for surgery in LAPCa?
Could surgery succeed alone?

3. Definitions Locally Advanced PCa includes: pT3ab pN0 M0 <pT4 pN1 M0
Very Heterogeneous definition
not all pT3a are the same
not all pT3b are the same
not all PN1 are the same
But they are all classified as “High risk” PCa
Locally Advanced PCa excludes:
pT4
pTx Nx M1

4. Definitions “High Risk PCa” is a too wide definition
1) biopsy Gleason score 8+
2) preoperative PSA 20+
3) TNM stage T3+
4) PSA>=20 or clinical stage T2c+ or biopsy Gleason score 8+
5) 5-year preoperative predicted probability of survival < 70%
6) PSA >=20 or clinical stage T3+ or Gleason score 8+
The definition is changing over the time1
And they are not all LAPCa: 22% are pT2N0 at DCSS
1. Foassati et al, BJU., 2015, in press

5. High Risk Prostate Cancer – Progression-Free Probability
With good technique, surgery results in excellent long term control of hi risk cancers
Yossepovitch O. et al, J Urol., 2007, 179, 493-9

6. High Risk Prostate Cancer – Progression-Free Probability
With good technique, surgery results in excellent long term control of hi risk cancers
Yossepovitch et al, J Urol, 2007, 179: 493-9

7. High Risk Prostate Cancer – Progression-Free Probability
With good technique, surgery results in excellent long term control of hi risk cancers
Yossepovitch et al, J Urol, 2007, 179: 493-9

8. The Specific Definition of High Risk Prostate Cancer Has Minimal Impact on Biochemical Relapse-Free Survival
Carvell T et al, J Urol, 2009, 181: 75-80

9. Risks
Akre et al, Eur Urol., 2011, 60:

10. Pre-op Diagnosis of LaPCa
Based today on
Clinical Stage: 43.8% of patients who had been previously staged as T3 actually had organ-confined tumors 1
PSA - level
- velocity ?
PBx
- Gleason score
- Ratio Pos. Cores / Neg. cores
- Infiltration / core length
- Ratio cancer length / overall core length
Negative Bone Scan
1.Van Poppel et al, Eur J Cancer, 2006,42:

11. Pre-op Diagnosis of LaPCa
What is the place today of
MRI
PET-Choline CT…
Proteinomics?
Genomics?
CTC?

12. MRI Diagnosis of LaPCa Sensitivity (95%CI) Specificity (95%CI)
Review of 75 studies, 9796 patients :
Sensitivity (95%CI) Specificity (95%CI)
ECE ( ) ( )
SVI ( ) ( )
overall T ( ) ( )
De Rooij et al, Eur Urol, 2015, epub

13. Rationale for surgery
1. Avoid late local events related to primary tumor
Retention
Hematuria
Bladder invasion
Ureteral invasion
Rectal invasion

14. Surgery increases OS and CSS
Zelefski et al, JCO, 2010, 28:

15. Surgery increases OS and CSS
Zelefski et al, JCO, 2010, 28:

16. Surgery increases OS and CSS
Zelefski et al, JCO, 2010, 28:

17. Surgery deletes primary site
Kim. et al, Cell., 2009, 139:

18. Surgical Quality Criteria
1. Surgical approach
2. Surgical margin status
2. Extended Pelvic Lymph Node Dissection

19. KM curve for BCR following radical prostatectomy for laparoscopic (black line) or open (gray line) : Surgical approach doesn’t matter.
PSA>=20, clinical stage T2C+ or biopsy Gleason grade 8+

20. Positive Surgical Margins at Radical Prostatectomy Predict Prostate Cancer Specific Mortality
Wright et al, JUrol, 2010, 183:

21. Positive Surgical Margins at Radical Prostatectomy Predict Prostate Cancer Specific Mortality
Wright et al, JUrol, 2010, 183:

22. Surgical Results at DCSS
pT3a +SM = 29%
pT3b +SM = 55%

23. Surgical Results at DCSS
Variable
p (95% CI)
pT3b stage
0.68 ( )
Positive margins
0.025 ( )
PSA
0.028 (1.03-1)
N° positive biopsies
0.64 ( ) GS ≤6
7 (referral) ≥8
0.9 (0-6.17)
0.005
0.9 (0-1.74)

24. Pelvic Lymph Node Dissection

26. Surgical Results at DCSS
PLND performed for LNI risk >2%
Number of nodes removed: median = 12; mean = 13

27. +PLN and Locally Advanced PCa at DCSS
%NX
pT2 67 33
pT3 63 25 12
pT3a 72 16
pT3b 36 62 2

28. Surgical Results at DCSS

29. Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy.
Touijer et al, EurUrol, 2014, 65:20-5

30. Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy.
Touijer et al, EurUrol, 2014, 65:20-5

31. Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy.
Touijer et al, Eur Urol, 2014, 65:20-5

32. Could Surgery alone succeed?
Role of aduvant EBRT
Role of aduvant HT+EBRT
Role of neo-adjuvant treatment
What is the population in which surgery is sufficient

33. Surgery + Adjuvant EBRT
Patients pT2-4 pN+ M0
Briganti et al, Eur Urol, 2011, 59:

34. Surgery + Adjuvant EBRT
536 pT3aN0/NX R1 with the required follow-up data
Karl et al, Radiot Oncol, 2015, 116:

35. Neo-adjuvant HT + Surgery
Long-term follow-up of 3-month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial
Yee, BJU, 2010, 105:

36. Neo-adjuvant Trt + Surgery
1. A Phase 2 Open-Label, Randomized, Multi-center Study of Neoadjuvant Abiraterone Acetate (CB7630) Plus Leuprolide Acetate and Prednisone Versus Leuprolide Acetate Alone in Men With Localized High Risk Prostate Cancer.(NCT )
Closed, March 2012
Primary Outcome Measures: Testosterone Concentration in Prostate Tissue
…/…
2. A Randomized, Open-Label, Phase 2 Study of MDV3100 as a Neoadjuvant Therapy for Patients Undergoing Prostatectomy for Localized Prostate Cancer (NCT )
Primary Outcome Measures: Pathologic Complete Response Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]Pathologic complete response rate following triplet therapy (enzalutamide in combination with leuprolide and dutasteride) and enzalutamide alone when administered as neoadjuvant therapy for 6 months prior to prostatectomy in patients with localized prostate cancer. Pathologic complete response is defined as the absence of morphologically identifiable carcinoma in the prostatectomy specimen, as evaluated by the site pathologist using standard methods
…/…

37. Surgery in LAPCa Surgery has a premium role Quality of Surgery matters
control of local tumor
control of positive node(s)
Surgery alone can not do all for all
Diagnosis of LAPCa is still lacking