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

Characteristics of High Risk Prostate Cancer

Biochemical recurrence Metastasis

Death

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

The role of Robotic Radical Prostatectomy and Pelvic Lymph Node dissection in patients

with High Risk Prostate Cancer

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

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

Oncological Considerations during Robotic Radical Prostatectomy

Neurovascular Bundle Anatomy

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]

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%

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

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%

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 -

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%

Surgical Margin status

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

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%

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

Surgical Technique

Specimen processing in theatre

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

Secondary excision of neurovascular bundle

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%)

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)

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

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

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 -

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 -

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 -

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 -

�  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

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

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

Haptic Feedback

Augmented Reality Image guidance

Surgeon uses 3D MRI model superimposed on 3D stereo view highlighting subsurface anatomy

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

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