Shazia Bashir MD, MPH Gynecologic Oncologist Demystifying the Robot: The Role of Robotic Surgery in Gynecologic Oncology Shazia Bashir MD, MPH Gynecologic Oncologist

Disclosure I have no disclosures

Epidemiology • Most common gynecologic cancer diagnosed in women – Estimated new cases in 2015 54,870 – Estimated deaths in 2015 10,170 – Lifetime risk 1 in 37 Siegel et al. Cancer Statistics, 2015. CA Cancer J Clin 2015;65: 5-29

Endometrial Cancer

Best Practices • Gynecologic oncologists should be involved in the initial care of every woman diagnosed with endometrial cancer.

Steps in Complete Surgical Staging Peritoneal lavage for cytology Inspection of all peritoneal surfaces Total hysterectomy Bilateral salpingo-oophorectomy Pelvic/para-aortic node sampling Omental biopsy ( unfavorable histology) 6

Percent of radiation use by surgeon and FIGO stage

Surgical staging in endometrial cancer. “Clinical estimation of depth of invasion, with or without frozen section, is inaccurate and may lead to underestimation of disease status when surgical staging is not performed. The practice of resecting only clinically suspicious nodes should be discouraged as it is no substitute for comprehensive surgical staging. Comprehensive surgical staging provides proper guidance for postoperative adjuvant therapy, avoiding needless radiation in 85% of clinical stage I/II patients” Kirby TO, Leath CA 3rd, Kilgore LC. Oncology 2006

What is “Adequate” Staging? 352 women surgically staged for endometrial cancer Lymph node count did not impact rate of node positivity Number of nodal stations sampled was an accurate predictor of node status SEER database.

What is “Adequate” Staging? Ability to assess full extent of disease Chan JK et al., “Lymphadnectomy in endometrioid uterine cancer staging: how many lymph nodes are enough? A study of 11,443 patients.” Cancer 2007 109(12):2454-60 Increasing number of lymph nodes removed associated with higher likelihood of identifying those with lymph node metastases Largest increase in probability of detection was when 21-25 lymph nodes were removed. >25 lymph nodes did not significantly improve detection rate SEER database.

Is Laparoscopic Hysterectomy and staging equivalent to Laparotomy?

Laparoscopy vs. Laparotomy in the Management of Endometrial Cancer Retrospective review of 510 endometrial cancer patients Surgical intent TLH in 226 and TAH in 284 11 conversions to laparotomy in the TLH group Median f/u 29 months. No difference in recurrence pattern, DFS or OS between groups King Edward Memorial Hospital for Women, Subiaco, WA, Australia. andreas_obermair@health.qld.gov.au OBJECTIVE: The impact of laparoscopic surgery on the patterns of recurrence and on prognosis in patients with endometrial cancer remains unclear. The objective of the current study was to evaluate the effect of the laparoscopic approach on patterns of recurrence, disease-free (DFS), and overall survival (OS) in patients with endometrial cancer. METHODS: A retrospective review of patients presenting with stages 1-4 endometrial cancer who had a hysterectomy, bilateral salpingo-oophorectomy with or without surgical staging was performed. Patients either had a total laparoscopic hysterectomy (TLH) or a total abdominal hysterectomy (TAH). Patterns of recurrence, DFS and OS were the study endpoints. RESULTS: The surgical intent was TLH in 226 patients (44.3%) and TAH in 284 patients (55.7%). TLH was converted to laparotomy in 11 patients. Patients for TLH were younger, heavier, and had a higher ASA score and were more likely to present with early-stage, well-differentiated tumors and were less likely to have undergone lymphadenectomy. Median follow-up was 29.4 months. DFS and OS were adversely and independently affected by increasing age, higher stage, higher grade, and by deeper myometrial invasion, whereas the intention to treat (TLH vs. TAH) did not influence DFS or OS. Patterns of recurrence were similar in both groups and no port-site metastasis was noted in the TLH group. CONCLUSIONS: The incidence of port-site metastasis in early-stage endometrial cancer treated by TLH is low. Laparoscopic management does not seem to worsen the prognosis of patients with endometrial cancer Obermair A. et al. Gynecol Oncol 2004

Laparoscopy vs. Laparotomy in the Management of Endometrial Cancer Prospective, randomized study of 122 endometrial cancer patients Surgical intent laparoscopy in 63 and laparotomy in 59 Median f/u 44 months. 12.6% recurrence in laparoscopic group vs. 8.5% with laparotomy (P>.05) King Edward Memorial Hospital for Women, Subiaco, WA, Australia. andreas_obermair@health.qld.gov.au OBJECTIVE: The impact of laparoscopic surgery on the patterns of recurrence and on prognosis in patients with endometrial cancer remains unclear. The objective of the current study was to evaluate the effect of the laparoscopic approach on patterns of recurrence, disease-free (DFS), and overall survival (OS) in patients with endometrial cancer. METHODS: A retrospective review of patients presenting with stages 1-4 endometrial cancer who had a hysterectomy, bilateral salpingo-oophorectomy with or without surgical staging was performed. Patients either had a total laparoscopic hysterectomy (TLH) or a total abdominal hysterectomy (TAH). Patterns of recurrence, DFS and OS were the study endpoints. RESULTS: The surgical intent was TLH in 226 patients (44.3%) and TAH in 284 patients (55.7%). TLH was converted to laparotomy in 11 patients. Patients for TLH were younger, heavier, and had a higher ASA score and were more likely to present with early-stage, well-differentiated tumors and were less likely to have undergone lymphadenectomy. Median follow-up was 29.4 months. DFS and OS were adversely and independently affected by increasing age, higher stage, higher grade, and by deeper myometrial invasion, whereas the intention to treat (TLH vs. TAH) did not influence DFS or OS. Patterns of recurrence were similar in both groups and no port-site metastasis was noted in the TLH group. CONCLUSIONS: The incidence of port-site metastasis in early-stage endometrial cancer treated by TLH is low. Laparoscopic management does not seem to worsen the prognosis of patients with endometrial cancer Tozzi et al. J Minim Invasive Gynecol 2005

Laparoscopy vs. Laparotomy in the Management of Endometrial Cancer DFS 87.4% vs 91.6% in laparoscopy vs laparotomy (P> .05) OS 82.7% vs 86.5% (P>.05) Stage I pts: DFS 91.2% vs 93.8% (P>.05) King Edward Memorial Hospital for Women, Subiaco, WA, Australia. andreas_obermair@health.qld.gov.au OBJECTIVE: The impact of laparoscopic surgery on the patterns of recurrence and on prognosis in patients with endometrial cancer remains unclear. The objective of the current study was to evaluate the effect of the laparoscopic approach on patterns of recurrence, disease-free (DFS), and overall survival (OS) in patients with endometrial cancer. METHODS: A retrospective review of patients presenting with stages 1-4 endometrial cancer who had a hysterectomy, bilateral salpingo-oophorectomy with or without surgical staging was performed. Patients either had a total laparoscopic hysterectomy (TLH) or a total abdominal hysterectomy (TAH). Patterns of recurrence, DFS and OS were the study endpoints. RESULTS: The surgical intent was TLH in 226 patients (44.3%) and TAH in 284 patients (55.7%). TLH was converted to laparotomy in 11 patients. Patients for TLH were younger, heavier, and had a higher ASA score and were more likely to present with early-stage, well-differentiated tumors and were less likely to have undergone lymphadenectomy. Median follow-up was 29.4 months. DFS and OS were adversely and independently affected by increasing age, higher stage, higher grade, and by deeper myometrial invasion, whereas the intention to treat (TLH vs. TAH) did not influence DFS or OS. Patterns of recurrence were similar in both groups and no port-site metastasis was noted in the TLH group. CONCLUSIONS: The incidence of port-site metastasis in early-stage endometrial cancer treated by TLH is low. Laparoscopic management does not seem to worsen the prognosis of patients with endometrial cancer Tozzi et al. J Minim Invasive Gynecol 2005

GOG LAP-2 Protocol LAVH/BSO + R A N D pelvic & para-aortic LND R A N D O M I Z E Endometrial adenocarcinoma or uterine sarcoma Clinical stage I., IIA Grade 1, 2, 3 The Gynecologic Oncology Group (GOG) LAP 2 trial is a large, prospective, randomized trial designed to determine equivalency in early-stage endometrial cancer outcomes of laparoscopically assisted vaginal hysterectomy/bilateral salpingo-oophorectomy (LAVH/BSO) with surgical staging when compared with traditional laparotomy with a total abdominal hysterectomy (TAH)/BSO with surgical staging. The accrual goal was achieved in September 2005. Only 11 of 52 GOG institutions (21%) have participated in LAP-2 TAH/BSO + pelvic & para-aortic LND

GOG LAP-2 N = 2616 enrolled, 2213 evaluable 23.7% required conversion to laparotomy LOS shorter in scope group (3 v 4 days) Operative time longer in scope group QOL same after 30 days Scope arm less likely to sample PA nodes No difference in stage, node positivity, cytology No difference in progression-free or overall survival Background: Feasibility of laparoscopy has been demonstrated, but the toxicity, staging, and survival has not been adequately compared to the traditional open approach. A randomized Phase III trial of 2616 patients was conducted by the GOG from 5/1996 to 9/2005. QOL and complications of surgery were previously reported at SGO. FIGO pathologic staging is the basis of this report. Methods: Clinical Stage I-IIA uterine cancer were eligible, consenting to either technique. The randomization procedures yielded two on laparoscopy arm for every one on the laparotomy arm. Scope participants were required to undergo laparotomy if the complete surgical staging was not feasible, or for resection of cancer. The staging results include: FIGO surgical stage, peritoneal cytology, number of nodes per site, and percent positive nodes at each location: right pelvic, left pelvic, right para-aortic, left para-aortic. Results: 2616 were randomized, 403 were excluded for this analysis: 84 ineligible, 76 sarcoma, 198 incomplete data, 45 were stage IV, leaving 2213 evaluable for lymph node staging of endometrial carcinoma (781 open:1432 scope). Conversion to laparotomy from laparoscopy occurred in 23.7%. Positive or suspicious cytology was found in 5.6% of laparotomy and 7.8% of laparoscopy participants (p = 0.055 n.s.). Pelvic nodes were documented (R 98.8% vs 98.9%, L 98.5% vs 98.1% n.s.) and positive pelvics (any positive 8.8% vs 8.7%; R 5.5% vs 5.8%; L 6.9% vs 6.1% n.s.) were similar. Laparoscopic surgical staging cases were less likely to have para-aortic nodes sampled (L 91.3% vs 85.0% p < 0.001; R 96.0% vs 92.5% P = 0.001), but positve nodes were no different (any positive PA 5.0% vs 4.5%; R 4.1%, 3.4%; L 2.3%, 2.7% n.s.). Final FIGO Staging results (III A: 5.5% vs 5.7% n.s.& IIIC: 9.3% vs 9.5% n.s.) were the same by randomization arm. Conclusion: These results demonstrate that laparoscopic surgical staging of endometrial cancer can be completed in 76.3%. No difference in postive cytology, node positivity rate, or FIGO stage could be attributed to the laparoscopic approach. Conversion to laparotomy is advised when incomplete staging results would yield inadequate information for treatment planning. NCI Funding: UO1CA65221, CA 27469.

Automated Endoscopic System for Optimal Positioning (AESOP) Released by Computer Motion in 1994 First robot to receive FDA clearance Single surgical arm for voice-activated camera positioning

ZEUS Surgical Robotic System Released by Computer Motion in 1998 Uses AESOP technology for camera movement 2 surgical arms and 2D optics available on console

Da Vinci Robotic System

DaVinci Robot First approved in 2000 (2005 for gynecological laparoscopic procedures) 1,571 systems worldwide Compared to open: Minimally invasive Improved visualization Reduction of tremors

Appeal of Robotics Compared to laparoscopic: 3-dimensional view Lack of fulcrum effect Improved range of motion (7 degrees of freedom) – exceeds natural range of motion Reduction of tremors Seated position for the surgeon

Appeal of Robotics

Concern of Robotics Cost Positioning Lack of haptic feedback Setup time Learning curve

Robotic Versus Laparoscopic Staging of Endometrial Cancer Boggess et al., 2008 AJOG: open (n=138) vs. lap (n=81) vs. robot (n=103) Robot-assisted Most LN: 32.9 (vs. 23.1 lap and 14.9 open) Shortest LOS: 1.0 (vs. 1.2 lap and 4.4 open) Least EBL: 74.5 (vs. 145.8 lap and 266 open) Less complications: 5.8% (vs. 29.7% open) Laparoscopic: longest OR time (213min, vs. 191 robot and 146 open)

Cost of Robotic Surgery Barnett et al., 2010 Obstet Gynecol: decision model Laparoscopy $10,128 vs. robot $11,476 vs. open $12847

Cornell Experience: Robotic versus Laparoscopic Staging in Endometrial Cancer Design: retrospective review Study Group: 118 subjects Assignment: surgeon/patient choice Dates: 5/2006 – 10/2010 Data obtained from: chart review of operative and pathology reports

Methods Data analysis performed using SPSS® 16.0 Pearson c2, Fisher’s exact tests used for categorical data Mann-Whitney U test used for comparison of non-normally distributed continuous data (LOS, EBL) Student’s t-test used for comparison of normally distributed continuous data Graphs generated using Microsoft Excel®

Results 118 patients who underwent surgical treatment for endometrial cancer via MIS 39 laparoscopic/79 robotic assisted No difference in mean age between laparoscopic and robotic patients (60.8 vs 60.9 years) No difference in BMI between laparoscopic and robotic (28.3 vs. 29.6, p=.38)

Results Trend towards longer operating time with robotic assistance (204.3 vs. 226.9 minutes, p=0.05) No difference in EBL (100mL vs. 100mL, p=0.633)

Results Significantly more likely to perform LND with robotic assistance No difference in operating time when comparing only patients undergoing complete surgical staging(214 vs. 220, n=32 vs. 75, p=0.353) Significantly more total number of lymph nodes removed (18.1 vs. 22.8, p<0.05) with robotic assistance

Results Trend towards more likely to perform para-aortic LND with robotic assistance No significant difference in number of para-aortic lymph nodes removed (4.4 vs. 5.8, p=0.228)

Results No significant difference in frequency of complications (2.5% vs. 6.3%, p=0.662) No difference in length of hospital stay (2 days vs. 2 days, p=0.986)

Robotic Surgery Learning Curve Significantly shorter case time in last 25 cases compared to first 25 cases (207.9 vs. 245.0 min, p=0.01) Compare robot last 25 to lap (compare only LN done to LN done) time and LOS [does it come close once one passes the learning curve]

Robotic Surgery Learning Curve No difference in EBL in last 25 cases compared to first 25 cases (129mL vs. 150mL, p=0.417)

Robotic Surgery Learning Curve No significant difference in whether lymphadenectomy was performed between first 25 and last 25 cases

Robotic Surgery Learning Curve Significantly more total# of LN removed (18.6 vs. 25.9, p<0.01)

Robotic Surgery Learning Curve Significantly shorter length of stay in last 25 cases compared to first 25 cases (2 vs. 1 day, p<0.05) Less pain? (Pothuri data)

Robotic Surgery Learning Curve No significant difference in complication rate between first 25 and last 25 cases

Summary Laparoscopic Robot Blood Loss 141.8ml 129ml (p=.66) Surgery Time 201.4 207.9 (p=.57) Lymph node yield 14.3 25.8 (p< .001) Complications 3.85% 2.56% (p=1) Hospital stay 1.9 1.38 (p=.02)

Summary Robot-assisted laparoscopic staging: more likely to perform pelvic lymphadenectomy, higher lymph node yield. Trend towards more likely to perform paraaortic lymphadnectomy No difference in operative time No difference in EBL or complications Shorter hospital stay for robotic assisted staging There is a learning curve associated with robotic-assisted laparoscopic staging Minimally invasive techniques: more likely to perform pelvic lymphadnectomy, less blood loss, shorter hospital stay. Trend towards less complications

Discussion Strengths Weaknesses Single surgeon Not random assignment Did not assess long-term follow-up Did not assess costs

Hysterectomy - 2005 518,828 Hysterectomies 64% Abdominal 22% Vaginal 14% Laparoscopic It was reported in November of 2009 in the American College of Obstetricians and Gynecologists that the nationwide use for laparoscopic hysterectomy had only reached 14% while abdominal hysterectomy rates were 64% and vaginal hysterectomy was 22%. This data was based on a cross sectional analysis from 2005 nationwide inpatient sample. How can this be?

Robotic Surgery Adoption: Total US Hysterectomy Market 525,000 Hysterectomies Annually in the US Dynamic Growth Phase % Penetration July, 2011 Quarterly Time Period

Robotic Surgery Adoption: US Malignant Hysterectomy Market 55,000 Malignant Hysterectomies Annually in the US Dynamic Growth Phase July, 2011 % Penetration Quarterly Time Period PN 873930 Rev. C

What do you think is the most likely explanation for the increased acceptance of robotic surgery?

1. Faster learning curve compared to traditional laparoscopy 2 1.Faster learning curve compared to traditional laparoscopy 2. Improved patient outcomes compared to traditional laparoscopy 3. Marketing tool to attract patients and increase surgical volume

Acknowledgements Thank you to Kevin Holcomb MD and Billy Burke MD Cornell and Columbia University Questions?