I have no financial disclosures. Controversies with Morcellation. Fibroids. Risk of morcellation malignancy. Morcellation 11/09/2014

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1 Controversies with Morcellation I have no financial disclosures Lilian T. Gien, MD, MSc, FRCSC Division of Gynecologic Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Assistant Professor, University of Toronto Benign Most common pelvic tumor in women Presentation: Abnormal uterine bleeding, pelvic pain Management Medical, surgical, radiologic Fibroids Morcellation Fragmenting a surgical specimen into smaller pieces Power/ electromechanical morcellation (EMM) FDA approved 1995 Rotating cylindrical blade to cut in smaller strips Laparoscopic approach made possible Risk of morcellation malignancy Occult cancer Uterine sarcoma Endometrial cancer Cervical cancer Intraperitoneal dissemination Negative impact on prognosis Difficult to interpret pathologic specimen Risk of recurrence adjuvant treatment Decreased overall survival 1

2 Sarcomas 7 8% of all uterine cancers Leiomyosarcoma: approx 40% of all sarcomas Aggressive Rare Endometrial stromal sarcoma Oct 2013: Amy Reed surgery Recent Events Dec 2013: Wall Street Journal article Statement from Society of Gynecologic Oncology Jan 2014: Task force by AAGL to examine risks of power morcellation Feb/March 2014: Brigham & Women s, Mass General, Temple Univ only can morcellate within a bag April 2014: FDA statement discourages the use of laparoscopic power morcellation during hysterectomy or myomectomy for uterine fibroids. May 2014: Health Canada statement on Laparoscopic Electric Morcellators Risk of Spread of Unsuspected Uterine Sarcoma. Objectives Can we minimize the risks of morcellation preoperatively? Intraoperatively? Postoperatively what is the prognosis and treatment options for a morcellated malignancy? Where do we stand with morcellation? Clinical history Risk factors for uterine sarcoma Age (mean age of diagnosis: 60) Race (Black 2x higher incidence) Menopausal status Previous tamoxifen use (>/= 5 yrs) Previous pelvic radiation Rare conditions: hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome, survivors of childhood retinoblastoma History of rapid uterine growth Not reliable Retrospective review of 580 leiomyosarcomas (LMS), <3% had a rapidly enlarging uterus Same review: 1 LMS found in 371 women with operation for rapidly growing fibroids (Parker et al., Obstet Gynecol 1994) Rule out endometrial/ cervical pathology If abnormal uterine bleeding BIOPSY Endometrial biopsy Cervical biopsy if cervix looks abnormal Notes: Pap smears are not diagnostic negative endometrial biopsy does not rule out malignancy 2

3 Imaging = not predictive Ultrasound MRI Features that suggest leiomyosarcoma are also features consistent with benign degenerating fibroids Large size, heterogeneity, central necrosis Imaging studies Goto et al., 2002: Prospective study 130 with degenerating uterine myoma, 10 with LMS Dynamic gadopentetate dimeglumine enhanced MRI combined with serum analysis of LDH Differentiated LMS vs fibroids with 100% PPV & NPV Has not been replicated Sato et al., 2014: MRI Diffusion weighted imaging Retrospective study 81 specimens, including 5 LMS Comparison to postop pathology: PPV 66.7%, NPV 100% Need confirmation of data, larger study Bottom Line: There is no definitive diagnostic modality that can reliably identify leiomyosarcomas from benign leiomyomas Occasional cases of malignancy can be identified preoperatively Should make an effort to use what we have Intraoperative Assessment Frozen section not recommended Blood and mucin can result in artifact Intraoperative needle biopsy Sampling error Inadvertant cellular dissemination Exposure to adjacent structures or peritoneal cavity Bottom Line: No gross characteristics that can distinguish benign myoma from sarcoma Morcellation Bags Could use of an intraperitoneal bag during morcellation reduce tissue dissemination? No evidence that this can improve prognosis Technical challenges: Variability in size, shape, weight of uterine tissue Puncturing the bag Visualization of the mass within the bag suboptimal Visualization of structures external to the bag may be obscured Advanced laparoscopic skills to avoid complications Prognosis of Leiomyosarcoma Overall poor prognosis 40% alive at 5 years Recurrence rates and survival outcomes poor even in setting of early stage disease Apparent stage I II LMS 72% recurrence in first 2.5 yrs after diagnosis Median overall survival 52 months 3

4 Prognosis of Morcellated Leiomyosarcoma Studies are small, single centre, retrospective Park et al., 2011 Retrospective study, n=56 with stage I II LMS (25 with, 31 without morcellation) Tumor morcellation assoc with poorer overall survival (OR 3.11, p=0.038) Abdomino pelvic dissemination greater in pts with morcellation (44% vs 12.9%, p=0.032) Perri et al., 2009 Retrospective study, n=37 with Stage I LMS (21 intact hysterectomy vs 16 injured Disease free and overall survival both compromised in injured group Prognosis of Morcellated Leiomyosarcoma George et al., 2014 Retrospective study, n=58 (39 with hyst, 19 with intraperitoneal morcellation) Morcellation associated with increased risk of abdominal/pelvic recurrence (p=0.001) Shorter median recurrence free survival (10.8 months vs 39.6 months, p=0.002) Treatment options with morcellated malignancies Pathologic specimens difficult to interpret Margins, depth of invasion, size?adjuvant radiation?adjuvant chemotherapy Side effects of therapy Difficult to quantify if any benefit What is the prevalence of unsuspected sarcoma? Seidman et al., 2012 Retrospective review 1091 cases of morcellation for benign disease Unexpected diagnosis in 1.2% of cases 1 LMS, 1 ESS (0.2%), 10 leiomyoma variants Mortality associated with the single case of LMS Follow up Laparoscopy done in 7 cases Disseminated disease in 4/7 (64.3%) What is the prevalence of unsuspected sarcoma? FDA conducted a review of published and unpublished studies: included 9/18 studies Included 104 to 1429 patients 5 countries, Varying histopathologic criteria to define sarcoma Number of pts with unsuspected sarcoma = 0 7 Estimate = 1 in 352 undergoing hyst or myomectomy has unsuspected uterine sarcoma (0.0028) 1 in 498 has unsuspected LMS (0.0020) Issues with interpretation of data All studies were single institution and retrospective True incidence of LMS could not be calculated because the overall hysterectomy rate was not known High volume academic medical or cancer centres Reports did not clarify whether the procedures were performed at that centre or referred for sarcoma treatment Unclear whether all candidates underwent a comprehensive preoperative evaluation and were appropriate candidates for MIS Some women diagnosed preoperatively not MIS candidates to begin with Many women with morcellation were postmenopausal 4

5 What is the prevalence of unsuspected sarcoma? Wright et al., JAMA 2014 Used a large insurance database to investigate prevalence of underlying cancer in uterine morcellation Morcellation in 15.7% of MIS hysterectomies Uterine cancer prevalence in morcellated specimens: 27/ (0.0027) Prevalence of unsuspected sarcoma Not well defined Difficult to determine based on retrospective data Need for population based data, prospective data, national registry to determine true incidence AAGL statement to FDA, July 2014 Decision analysis to examine the risk of LMS in a population who are candidates for power morcellation The combined mortality from LMS + morcellation is less than that of open hysterectomy Converting all LPSC hysts with power morcellation to open hyst = annual increase of 17 more women dying from surgery each year, and increase in morbidity What can be done? Preoperative assessment History and physical Imaging Intraoperative Frozen section Morcellation bags? INFORMED CONSENT Current guidelines/statements Society of Gynecologic Oncology (SGO) Position Statement Dec 2013 it is generally contraindicated in the presence of documented or highly suspected malignancy. should communicate about the risks, benefits, and alternatives of all procedures so that a patient is able to make an informed and voluntary decision FDA April 2014 do not use laparoscopic uterine power morcellation in women with suspected or known uterine cancer inform patients that their fibroid(s) may contain unexpected cancerous tissue and that laparoscopic power morcellation may spread the cancer, significantly worsening their prognosis. Current guidelines/statements ACOG Special Report May 2014 strongly suspected or known malignancy, power morcellation should not be used Informed consent risks, benefits and alternative treatments Possible occult cancer and possible dissemination AAGL Task Force May 2014 use morcellation only after appropriate and reassuring evaluation of the myometrium, cervix, and endometrium. consider alternatives to morcellation in postmenopausal women obtain informed consent, including a thorough discussion of risks and benefits, from women considering electromechanical morcellation. 5

6 Current guidelines/statements Health Canada May 2014 recognize the prevlaence of unsuspected uterine sarcoma in patients under consideration for hysterectomy or myomectomy for the treatment of uterine fibroids Consider the treatment alternatives and review these options with each prospective surgical patient. Be aware and inform patients that laparoscopic electric morcellation of unsuspected uterine sarcoma during hysterectomy or myomectomy may disseminate the disease and negatively impact prognosis. Informed Consent Amy Reed was diagnosed with Stage IV leiomyosarcoma after uterine morcellation to remove fibroids Had preoperative MRI and biopsy Says she WAS NOT TOLD the risks that it might upstage any undetected cancer. Future Directions Research to develop better preoperative diagnostic tools Determine the true incidence of LMS and risk of dissemination Nationwide prospective surgical database to accurately quantify outcome data with regard to uterine surgery Safety measures to allow continued morcellation Is the decision being made regardless? FDA statement: the FDA discourages the use of laparoscopic power morcellation during hysterectomy or myomectomy for uterine fibroids. Johnson & Johnson: Suspended sales of 3 power morcellators Some hospitals no longer performing power morcellation, or required to morcellate within a bag Conclusions Morcellation of an occult uterine sarcoma can reduce a patient s disease free and overall survival There is no definitive preoperative/ intraoperative test that can diagnose a uterine sarcoma Postmenopausal status Endometrial biopsy Consider morcellation within an enclosed system Informed consent: risk of occult malignancy, dissemination of disease, which can lead to worse prognosis 6