Carcinoma of the Cervix. Kathleen M. Schmeler, MD Associate Professor Department of Gynecologic Oncology

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1 Carcinoma of the Cervix Kathleen M. Schmeler, MD Associate Professor Department of Gynecologic Oncology

2 Cervical Cancer Treatment

3 Treatment Microinvasive (Stage IA1): Simple (extrafascial) hysterectomy/cone Early Stage (IA2 or IB1): Radical hysterectomy/trachelectomy vs. chemoradiation Locally Advanced (IB2-IVA) Primary chemoradiation (cisplatinum) Distant Metastases (IVB) Palliative care/systemic chemotherapy

4 Treatment of Early Stage Disease Stage IA1-IB1

5 Surgical Options Early Stage Cancer Cervical Stage IA1 Simple hysterectomy Cervical conization (preserve fertility) Stage IA2-IB1 Radical hysterectomy with lymphadenectomy Radical trachelectomy with lymphadenectomy (preserve fertility)

6 Simple vs. Radical Hysterectomy

7 Radical Trachelectomy Fertility Preservation

8 Radiotherapy as Primary Treatment for Stage IA2-IB1 Option for poor surgical candidates: medical comorbidities poor performance status SEER Registry: 4,000 women with early stage disease Primary surgery had a 59% reduction in death compared with RT (HR 0.41, 95% CI ) Bansal et al, Amer J Obstet Gynecol, 2009

9 Who Needs Postoperative High-risk disease: Radiotherapy? Positive surgical margins, positive lymph nodes, parametrial involvement Chemoradiation Intermediate-risk disease: Sedlis Criteria (GOG 92) Radiation vs. chemoradiation controversial (ongoing prospective study GOG 263) Sedlis et al, Gynecol Onc, 1999, GOG 92 Peters et al, JCO, 2000, GOG 109

10 Sedlis Criteria GOG 92 Randomized 277 patients with at least 2 of the following risk factors to postoperative RT vs. observation: >1/3 stromal invasion Capillary lymphatic space involvement Tumor diameter > 4 cm Recurrent disease 15% (RT) vs. 28% (Observation) Grade 3/4 toxicities were increased in the RT group (6% vs. 2%) Sedlis et al, Gynecol Onc, 1999 Rotman et al, Int J Rad Bio Phys, 2006

11 Postoperative Radiotherapy Sedlis Criteria Sedlis et al, Gynecol Onc, 1999

12 Early Stage Disease Summary Stage IA1: Simple hysterectomy or conization Stage IA2-IB1: Radical hysterectomy of trachelectomy Primary RT if poor surgical candidate Post-operative chemort if high-risk disease Post-operative RT if intermediate-risk disease (Sedlis criteria)

13 Treatment of Locally Advanced Disease Stage IB2-IVA

14 Locally Advanced Disease Stage IB2-IVA 1. Primary chemoradiation** 2. Neoadjuvant chemotherapy (NACT) followed by radical hysterectomy +/- chemoradiation

15 Primary Chemoradiation Radiotherapy: External beam Whole pelvis Extended field if positive paraaortic nodes Intracavitary (Brachytherapy) Tandem and ovoids

16 Primary Chemoradiation Adding weekly cisplatin to primary radiation therapy decreases rate of death by 30-50% Has been confirmed in several randomized trials and a meta-analysis NCI clinical announcement in concurrent cisplatinum-based chemotherapy and RT are standard of care in the treatment of locally advanced cervix cancer

17 Primary Chemoradiation RTOG 90-01

18 Primary Chemoradiation RTOG women with stage IB-IVA cervical cancer (>5 cm tumor) Randomized to: Pelvic and para-aortic RT vs. Chemoradiation with pelvic only RT combined with cisplatin and 5-FU Morris et al, NEJM, 1999

19 Primary Chemoradiation 5y survival was 73% (chemort) vs. 58% (RT alone) (p=0.004) Lower rates of distant metastases and regional recurrences in chemort group (p<0.001) ChemoRT group had higher rate of reversible hematologic side effects RTOG Morris et al, NEJM, 1999

20 Chemoradiation: Risk of Death Decreased by 30-50%

21 Primary Chemoradiation Primary chemoradiation is the preferred approach for women with locally advanced cervical cancer (IB2- IVA) There is a 30-50% reduction in death with chemoradiation with cisplatin compared with RT alone Weekly cisplatin (40 mg/m 2 ) appears comparable to 2 cycles of cisplatin/5- FU and has fewer adverse effects

22 Locally Advanced Disease Summary: Stage IB2-IVA Primary chemoradiation is the treatment of choice Neoadjuvant chemotherapy followed by surgery and/or chemoradiation is an option if RT not available

23 Summary Cervical cancer is preventable: Effective vaccines Treatable pre-invasive disease Early stage disease: Surgery (radical hysterectomy, trachelectomy) Locally advanced disease: Chemoradiation Recurrent disease: Pelvic exenteration only curative option Metastatic disease: Palliative chemotherapy

24 Thank You