Lister Urology Update meeting with The Dutch Urological Society, Hertfordshire and South Bedfordshire Urological Cancer Centre; 10/2014

2. Introduction
™ Management of high-risk PCa is of key importance for the
practicing urologist
™ Despite prostate-specific antigen (PSA)-based awareness and
early detection guidelines, approximately 15-30% of PCa
patients still present with high-risk (HR)
™ In the past, high-risk PCa patients were usually considered
candidates for nonsurgical therapies
™ However, the continuing improvement of surgical technique
and the new concept of multimodal therapy have made
surgery an option, and the number of operations performed
for high-risk PCa is now substantial

3. Characteristics of High Risk
Prostate Cancer
Biochemical recurrence
Metastasis
Death

4. Commonly used classifications and challenges in
the management of High Risk Prostate Cancer
• The biologic behaviour of HR cancer varies
• Current diagnostic tools lack staging accuracy
• Definitions of HR differ considerably,
making prognostic assessment and outcome comparisons between
treatments challenging

5. The role of Robotic Radical Prostatectomy
and Pelvic Lymph Node dissection in patients
with High Risk Prostate Cancer

6. Robotic Surgical considerations in
High Risk Prostate Cancer
™ Approximately 20 – 65% of HR patients have organ-confined
(OC) disease at RP, and these men experience
excellent long-term survival while avoiding exposure to
long-term androgen-deprivation therapy (ADT )
™ Despite the higher likelihood of biochemical
recurrence and secondary therapy, HR patients have
10-yr cancer- specific survival (CSS) estimates after RP
of approximately 90%
™ EUA guidelines now support a role for RP in select HR
patients as a treatment option that may include a
multimodality approach

7. Aims of Robotic Prostatectomy
and ePLND in high risk patients
™ Oncological Outcomes
™ Negative Margins
™ Extended Lymph node dissection
™ Peri-operative Outcomes
™ No complications
™ Functional Outcomes
™ Erectile function
™ Urinary incontinence

8. Oncological Considerations during
Robotic Radical Prostatectomy

9. Neurovascular Bundle
Anatomy

10. The role of extended lymph node
dissection
Diagnostic , Prognostic
and Therapeutic impact
EAU recommends an
ePLND
58% of patients have
internal iliac involvement
[Burkard et al]

11. ePLND oncological outcomes
™ In current practice worldwide
there is no uniformity of
performing ePLND during
Robotic prostatectomy
™ In 4 large recent international
series the mean lymph node
yield is 18 nodes
™ The overall lymph node
positive status ranges from
1-33%
™ The procedure is associated
with an initial increase in
operative time (10 – 45 min)
™ Incidence of symptomatic
lymphocele was 3% (2.4-6.5%

12. Surgical case-series in high-risk prostate
cancer treated using multimodal therapy

13. Results from Open Radical Prostatectomy to
Robotic Radical Prostatectomy for High Risk
Ca Prostate
Briganti et al Yuh et al
Number of patients 1366 1360
Positive margin 45 % 35 %
Lymph Node positive rate 23 % 1 – 33%
BCRFS % 69 (5 Yr) 45-86 (3Yr)
Complication rate - 3 -30%

14. Perioperative outcomes
Study Cases Estimated
blood loss
(ml)
Operative
time
Length of
stay
Catheter
time
Ham 121 432 214 5.8 12.9
Zugor 147 183 164 - 5.7
Lavery 123 84 147 1.6 -
Rogers 69 150 175 1 7
Jayram 148 150 - 1 6
Sagalovich 82 150 111 - -
Yuh 30 200 186 1 -
Ou 148 100 150 3 8
Jung 200 150 190 4 -

15. Perioperative outcomes
™ Mean operative time = 168 minutes
™ Estimated blood loss = 189 ml
™ Mean length of stay = 3.2 – 7.2 days
™ Majpr complication rate = 3 – 30%

16. Surgical Margin status

17. Surgical Margin status
™ Average rate of organ confined disease is 35%
(7-48%)
™ Positive margin rate is 35% (12-53%)
™ In patients with PSA > 20 ng/ml increase risk of
™ Non organ confined disease
™ Positive margin
™ Lymph node positivity

18. Functional outcomes
™ Continence
™ 12 month continence rates using 0-1 pad = 78-95%
™ Continence with no pad = 51-95%
™ Erectile function
™ 12 months ranges from 52-60%

19. Drawing the balance between nerve sparing
and wide local incision in patients with high
risk prostate cancer
N Vasdev, S Agarwal, T Lane, G Boustead, J Adshead
• Thesis for ChM (Urol) at the Royal College of Surgeons of Edinburgh / University
of Edinburgh

20. Surgical Technique

21. Specimen processing in theatre

22. Pathology reporting of frozen
section results
™ A positive surgical margin on frozen section is reported
as the presence of one invasive malignant gland that
contact with the inked margin

23. Secondary excision of
neurovascular bundle

24. Impact on Nerve sparing
™ In patients with pT2/3 stage disease with intermediate
and high-risk prostate cancer, intrafascial nerve spare
increased from 67 % to 100% (p<0.0001) and in
patients with T3a disease from 42% to 100%
(p<0.0001).
™ In patients with T3b disease we did not perform an
intrafascial nerve spare and hence the increase was
from 0% to 100%)

25. Overall reduction of Positive
margins
™ In patients with T2 intermediate and high risk
prostate cancer (n=20) who did not undergo IOFS
analysis and a standard wide local excision, the
reduction in the T2 positive surgical margin rates
with the introduction of IOFS during robotic radical
prostatectomy was 17.8% to 0% (p<0.05)
™ In patients with T3 intermediate and high risk
prostate cancer (n=7) who did not undergo IOFS
analysis and a standard wide local excision, the
reduction in the T3 positive surgical margin rates
with the introduction of IOFS during robotic radical
prostatectomy was 34% to 20.2% (p=NS)

26. Current Follow up
™ At a current mean follow up of 8 months none of the
patients have had a biochemical recurrence and the
PSA at mean follow up 6 months (Range 2-12)
™ At a mean follow up of 8 months
™ reduction in the urinary incontinence from 37% in the
IOFS group versus 57% in the non-IOFS group (p=NS)
™ The incidence of patients having spontaneous erections
and not requiring a PDE-5 inhibitor for successful
intercourse is 32% in the IOFS versus 3% in the non-
IOFS group (p<0.05)
™ Longer follow up is required to evaluate the functional
data and we will publish our results in due course

27. Advantages to technique
™ Better Nerve sparing in patients with intermediate and
high risk disease
™ Improvement in patient functional outcomes
™ Reduction in positive margin rates and reduce risk of
adjuvant radiotherapy
™ Cost saving – PDE5, AMS, Adjuvant radiotherapy

28. Oncological outcomes
Cases
, n
Median
Follow up
Additional
therapy
(RT +/-
ADT)
Definition of
BCR
Recurrence
rates
Time to
recurrence
Shikanov 70 9.7 - PSA>0/1 1 yr BCRFS = 72 5.7
Zugor 147 19.6 - PSA≥0.2 RFS = 80 -
Connoly 160 26.2 - PSA>0.2 2 Yr BCRFS = 45 -
Lavery 123 12.5 - PSA>0.2 RFS = 74 4.6
Rogers 69 37.7 13 PSA≥0.2 1 yr BCRFS = 86 9.7
Jayram 148 18 23.3 - - -
Ou 148 26.7 - PSA>0.2 RFS = 80 -
Jung 200 22 9.0 PSA>0.2 RFS = 75 -

29. Oncological outcomes
Cases
, n
Median
Follow up
Additional
therapy
(RT +/-
ADT)
Definition of
BCR
Recurrence
rates
Time to
recurrence
Shikanov 70 9.7 - PSA>0/1 1 yr BCRFS = 72 5.7
Zugor 147 19.6 - PSA≥0.2 RFS = 80 -
Connoly 160 26.2 - PSA>0.2 2 Yr BCRFS = 45 -
Lavery 123 12.5 - PSA>0.2 RFS = 74 4.6
Rogers 69 37.7 13 PSA≥0.2 1 yr BCRFS = 86 9.7
Jayram 148 18 23.3 - - -
Ou 148 26.7 - PSA>0.2 RFS = 80 -
Jung 200 22 9.0 PSA>0.2 RFS = 75 -

30. Oncological outcomes
Cases
, n
Median
Follow up
Additional
therapy
(RT +/-
ADT)
Definition of
BCR
Recurrence
rates
Time to
recurrence
Shikanov 70 9.7 - PSA>0/1 1 yr BCRFS = 72 5.7
Zugor 147 19.6 - PSA≥0.2 RFS = 80 -
Connoly 160 26.2 - PSA>0.2 2 Yr BCRFS = 45 -
Lavery 123 12.5 - PSA>0.2 RFS = 74 4.6
Rogers 69 37.7 13 PSA≥0.2 1 yr BCRFS = 86 9.7
Jayram 148 18 23.3 - - -
Ou 148 26.7 - PSA>0.2 RFS = 80 -
Jung 200 22 9.0 PSA>0.2 RFS = 75 -

31. Oncological outcomes
Cases
, n
Median
Follow up
Additional
therapy
(RT +/-
ADT)
Definition of
BCR
Recurrence
rates
Time to
recurrence
Shikanov 70 9.7 - PSA>0/1 1 yr BCRFS = 72 5.7
Zugor 147 19.6 - PSA≥0.2 RFS = 80 -
Connoly 160 26.2 - PSA>0.2 2 Yr BCRFS = 45 -
Lavery 123 12.5 - PSA>0.2 RFS = 74 4.6
Rogers 69 37.7 13 PSA≥0.2 1 yr BCRFS = 86 9.7
Jayram 148 18 23.3 - - -
Ou 148 26.7 - PSA>0.2 RFS = 80 -
Jung 200 22 9.0 PSA>0.2 RFS = 75 -

32. ™ Robotic assisted laparoscopic radical prostatectomy
can be per- formed safely as salvage local therapy after
failed radiation therapy. Outcomes are comparable to
those of large series of open salvage prostatectomy

33. Newer techniques During Robotic
Prostatectomy for high risk prostate cancer
™ Fluoresce guidance during Robotic Prostatectomy
™ Haptic nano-sensor during Robotic Prostatectomy
™ Augmented reality image guidance

34. Fluorescence Guidance During Robotic
Radical Prostatectomy
™ Near-infrared (NIR) fluorescent dye indocyanine green
(ICG)
™ Results
™ 100% sensitivity
™ Identification of nodes outside the extended nodal
dissection

35. Haptic Feedback

36. Augmented Reality Image guidance
Surgeon uses 3D MRI model superimposed on 3D stereo view
highlighting subsurface anatomy

37. Conclusion
™ Robotic Prostatectomy + ePLND is a part of the
mutimodal therapy in patients with high risk prostate
cancer
™ Robotic Prostatetomy has the advantages
™ Histopathological assessment
™ Local disease control and risk of reduction of metastasis
™ Concomitant ePLND may improve survival and identify
patients in whom immediate ADT is indicated

38. Conclusion
A multimodal approach to therapy including
robotic prostatectomy, radiotherapy and
neoadjuvant and / or adjuvant ADT should be
offered to men with high risk prostate cancer
but optimal protocols remain to be determined