Minimally Invasive Surgery in Gynecologic Oncology Financial Disclosure “As it pertains to CME, I have no relevant financial relationships with any commercial interest to disclose.”

Minimally Invasive Surgery in Gynecologic Oncology William M. Merritt, MD April 2010 I would like to thank ____________ for this opportunity to speak at this months “For Women’s Only” series. Since moving back to Columbia from Houston, My wife and I truly feel like we are back home here in South Carolina. Today’s topic is an important one in medicine today, not only in cancer, but in our field of women’s care.

Objectives Reviews types of gynecologic cancer and treatments Minimally Invasive Surgery (MIS) Role of MIS in Gynecologic Oncology (and Gynecology) Patient benefits and risks with MIS Throughout the next 30 minutes I hope to provide you with information that will be helpful for you or your loved ones in understanding where our field is today in cancer care. First I will review the most common Gynecologic cancers we provide care for. Next, I will discuss the topic of MIS and more specifically the different types and there role in gynecologic cancer conditions, as well as some benign (non-cancerous) conditions. Lastly, I have prepared some slide with commonly asked questions that I hope will be informative. Following I know we will have time to discuss any additional questions that you have but please feel free to raise your hand or stop me at any point to ask a question. I would like to keep this as informal as possible.

2009 Estimates on Female Cancer Thousands © 2009, American Cancer Society, http://www.cancer.org

Ovarian Cancer 21,550 estimated new cases in 2009 Lifetime risk: 1.7% Average age: 59 Risk Factors: family history Symptoms Bloating Weight gain Abdominal discomfort Early satiety (feeling full) Nausea Detection: Pelvic exam Imaging (Ultrasound, CT Scan) Ca-125 OVA1 (recently FDA approved) Ovarian cancer is second most common gynecologic cancer today and continues to be one of the most difficult to treat. The lifetime risk of developing ovarian cancer is 1.7%; however women with strong family history of ovary and/or breast cancer may have an increased risk due to genetics. Symptoms for ovarian cancer are generally nonspecific. When you interview women with ovarian cancer you will often hear that these type of symptoms have been occuring daily for several weeks and are/were different from their normal self. There are no good screening tests for this disease but using combination of exam, U/S, and ca-125 testing will help with diagnosis for certain patients.

Endometrial/ Uterine Cancer Most common gynecologic cancer 42,160 new cases in 2009 Risk Factors: obesity, unopposed estrogen, no pregnancies Symptoms: Abnormal uterine bleeding Bleeding after menopause Detection: Pelvic exam Endometrial biopsy Pelvic ultrasound Endometrial or uterine cancer is the most common gynecologic cancer in the US and SC. Fortunately it is also very curable due to early detection. We know that women who have unopposed estrogen, that is not enough or no progesterone to the uterus are at high risk. HRT therapy has evolved to eliminate this possibility but unfortunately one of the main producers of estrogen is fat cells – hence obesity being a major risk factor. Women with AUB generally are evaluated with either a biopsy of U/S to confirm diagnosis.

Endometrioid UPSC/Clear Cell Present in earlier stage Present with advanced stage Stage I 73% 54% Stage II 11% 8% Stage III 13% 22% Stage IV 3% 16% 5-yr survival 85-90% 60% 70% 50% 40-50% 20% 15-20% 5-10% Gehrig et al, Gyn Onc 2010

Cervical Cancer 11,270 new cases in the 2009 Death rates decreasing due to early detection Risk factors: HPV infection Cigarette smoking Sexual activity at an early age (exposure) Symptoms: Abnormal vaginal bleeding Vaginal discharge Detection: Pelvic Exam Pap smear / HPV testing Cervical cancer is not nearly as common as it used to be thanks to PAP smears. Early detection of precancerous cells has led to a significant delice in new cases and in turn deaths due to ovarian cancer. With the introduction of HPV (or Human Papilloma Virus) testing – early detection and screening methods continue to improve. Not to head off on to far of a tangent – many of you may have heard of the HPV vaccine. I truly feel like the jury is still out on this. I can discuss this more later if you want.

Vulvar Cancer Rare: 4% of all gynecologic cancers Risk factors HPV Smoking Skin disorders of the vulva Symptoms Itching (itch scratch cycle) Vulvar mass / ulcer Bleeding Detection Pelvic exam Biopsy Vulvar cancer is even rarer than cervical cancer. Similar risk factors exist as for cervical cancer. Patients typically describe vulvar itching and bleeding. Diagnosis is made by biopsy.

Treatment Ovarian cancer Endometrial cancer Cervical cancer Surgery + chemotherapy Endometrial cancer Surgery ± radiation (± chemotherapy) Cervical cancer Surgery OR radiation + chemotherapy Vulvar cancer Surgery ± radiation Vagina Uterus Endometrium Myometrium Ovary Fallopian Tube Cervix Vagina Uterus Endometrium Myometrium Ovary Fallopian Tube Cervix Treatment for each of these cancers differs widely. This is mainly due to disease process itself. Ovarian cancer spreads like leaves off a tree. Goal at the time of surgery is take out all the visible cancer possible. Unfortunately, most patients that are diagnosed with ovarian cancer have disease already outside of the ovaries. For this reason, there is very little role for MIS. In a few cases, ovarian cancer is diagnosed in the early stage, i.e. confined to the ovary and these patients may be candidates for staging with MIS. Endometrial cancer spreads into the uterus, through the bloodstream and lymphatics. At the time of surgery, a hysterectomy with removal of tubes and ovaries are perfomed. In addition, staging procedures including removal of lymph nodes in the pelvis and abdomen maybe performed based on the tumor itself. Cervical cancer spreads by local extension, i.e. it invades tissue next to the cervix. It can also spread to lymph nodes. Upon diagnosis, patients are deemed surgical candidates based on size and stage of cancer. If surgery, then either a simple hysterectomy or radical hysterectomy is performed. Radical differs in that…… Vulvar cancer is treated typically by surgical resection of the tumor and regional lymph nodes. Patients may need additional therapy following in the form of XRT.

Surgical Options Traditional: Laparotomy Midline vertical Transverse So when patients go to the OR for cancer surgery, the traditional approach was to make a large incision. Usually either an up and down or low transverse incision was made. For most cancer cases, the vertical incision is preferred due to allowing access to the upper abdomen for exploration. Midline vertical Transverse

Minimally Invasive Surgery (MIS) An approach to surgery whereby operations are performed with specialized instruments designed to be inserted through small incisions or natural body openings Types Laparoscopic Robotic Over the past 15 years MIS has become a large part of surgical therapy not only in our field but others as well. MIS in a nut shell is defined as ……. Two types used in our specialty include.

What can be done with MIS Hysterectomy Supracervical Total Tubes and ovaries Myomectomy Removal of fibroids Lymph node dissection Pelvic Aortic Diagnostic (looking)

MIS – What’s so good about it? Less post-operative pain Shorter hospital stay Less blood loss Quicker return to normal activities Smaller incisions

Are there any drawbacks? Not all procedures are safe to do with MIS Time Learning curve Some cases take longer compared to traditional approach Cost

Role of MIS in endometrial cancer Feasibility Is it possible? Reproducible? Comparison with standard approach Better, worse, and equivalent? Risks/Benefits Acute Long term

Laparoscopy

Laparoscopy vs Laparotomy – GOG LAP2 Study Population (1996-2005) L/S: 1,696 Open: 920 Conversion rate: 434 (25.8%) Surgical Staging Lymph node dissection 99% (open) vs. 98% (L/S) Pelvic/aortic: 96% (open) vs. 92% (L/S) Aortic: 97% vs. 94% No difference in patients w/ advance surgical stage Walker et al, JCO 2009

Hospital stay >2days 845 94 867 52 Laparotomy (n=920) % Laparoscopy (n=1,248) P OR time (min) 130 204 <0.001 Hospital stay >2days 845 94 867 52 Complications -Vascular 29 4 75 5 -Post op fever 33 8 55 3 -Ileus/SBO 80 9 -Wound infection 53 -Transfusion 66 7 143 -Deaths 1 10 <1 -Bladder/Bowel 23 58 Walker et al, JCO 2009

What do the patients think? L/S (n=535) vs. open (n=267) Quality of life (FACT-G) Emotional Physical Social Functional well-well being 6 weeks L/S: better physical functioning and body image, less pain, earlier resumption of normal activities and return to work 6 months L/S: better body image Kornblith et al, Gyn Onc 2009.

Are there acute benefits? MIS (L/S and robotic; n=66) vs open (n=115) OR time (min) 284 vs 203 P<0.0001 EBL 300 vs 100 mL P<0.0001 Hospital stay 1 day vs 4 days P<0.0001 Median narcotic use (24 hr post op) 43 mg vs 10 mg (morphine equiv) P<0.0001 Nausea – MIS patients required less rescue antiemetics 24hr pos op Havrilesky et al, Gyn Onc 2009

Long term cancer benefit? L/S vs. Open (N) Follow up (months) Overall survival Disease free survival Cancer-related survival Tozzi et al 63 vs 59 44 82% vs 86% 87% vs 92% 25% (2/8) vs 40% (2/5) Zullo et al 40 vs 38 79 82% vs 84% 80% vs 82% 50% (4/8) vs 44% (4/7) Malzoni et al 81 vs 78 38.5 ??? No difference in survival recently reported for GOG LAP2 trial at 3-yr follow up Tozzi et al, J Minim Invasive Gynecol 2005 Zullo et al, Am J Obstet Gynecol 2009 Malzoni et al, Gyn Onc 2009

Cervical cancer No difference in recurrence or survival reported No. pts OR time (min) EBL (mL) Hosp. stay (d) Margins Complications Spirtos et al. All L/S 78 205 225 NR All negative 3 cystotomies 1 ureterovaginal fistula Abu-Rustum et al. L/S vs. open 17 vs. 195 371 vs. 295 301 vs. 693 4.5 vs. 9.7 No ureteral injuries or fistulas reported Frumovitz et al. 35 vs. 54 344 vs. 307 319 vs. 548 2 vs. 5 - 18% vs. 53% infectious morbidities - No noninfectious reported NR = not reported No difference in recurrence or survival reported Spirtos et al, AJOG 2002 Abu-Rustum et al, Gyn Onc 2003 Frumovitz et al, Obstet Gynec 2007

Robotic Surgery – What it isn’t…

Robotic Surgery- What it is…

Robotic Surgery da Vinci robot system is the only robotic surgical system is use today Benefits Improved visual fields Less dependence on surgical assistance Surgeon comfort Increased instrument mobility Drawbacks Cost Loss of tactile feedback Learning curve Availability Bulky machine Trochar size

Set-up

Set-up

Set-up

Instruments are controlled by the surgeon’s hands Robotic Instruments Instruments are controlled by the surgeon’s hands High range of motion for robotic instruments allow for addressing complex surgical issues

Comparison of 3 methods: open, L/S, robotic Open (n=138), L/S (n=81), & robotic (n=103) OR time: L/S (213 min) > robot (191) > open (147) Robot Better lymph node count Lower EBL 75 mL Lower hospital stay (1 day) Complication rate: Robot (6%) vs. open (30%) Conversion rate: L/S (5%) & robot (3%) No long term follow up reported Boggess et al, AJOG 2009

Is robotic surgery better than laparoscopy? Robot assisted Laparoscopy OR time (min) 2621 1692 1923 2061 1413 EBL (mL) 50 97 49 100 105 Hospital stay (days) 1 1.6 2 No difference in survival at 40 months (n=141)4 1. Leitao et al, Gyn Onc 2009 Lowe et al, Gyn Onc 2009 Nevadunsky et al, Gyn Onc 2009 Mendivil et al, Gyn Onc 2009

Robotics and cervical cancer No. patients EBL (mL) OR time (min) Hosp. stay (min) Kim et al 10 207 355 7.9 Fanning et al 20 300 390 1 Sert et al Robot vs. L/S 7 vs. 7 71 vs. 160 241 vs. 3000 4 vs. 8 Nezhat et al. 13 vs. 30 157 vs. 200 323 vs. 318 2.7 vs. 3.8 Boggess et al Robot vs. LAP 51 vs. 49 97 vs. 417 211 vs. 248 1 vs. 3.2 Kim et al, Gyn Onc 2008 Fanning et al, AJOG 2008 Sert et al, Int J Med Robot 2007 Nezhat et al, JSLS 2008 Boggess et al, AJOG 2008

Fertility preservation? Laparotomy / vaginal approach Traditional approach OR time: 163 to 253 min Recurrence rates: 2.7 to 7.3% Pregnancy (delivery >37 weeks) 60% Robotic approach 4 studies (8 pts total) OR time – 172 to 373 min EBL (mL) – 62 to 200 Hosp stay (d) – 1.5 to 3.5 Complications: 2 (edema & neuropathy) F/U: no recurrence in 105 d (Ramirez et al , Gyn Onc 2010) No pregnancies reported to date Dursun et al, EJSO 2007 Ramirez et al, Gyn Onc 2008 Ramirez et al, Gyn Onc 2010

Suturing During Hysterectomy

Conclusions MIS surgery is a reasonable option in gynecologic cancer Endometrial Cervical Ovary (early stage) Laparotomy, laparoscopy and robotic surgery offer advantages for patients short term but are equivalent in patient survival Robotic surgery offers surgeon advantages over laparoscopy