Society of Gynecologic Oncologists of the Philippine

Transcription

1 Philippine Society of Oncologists, Inc. Rm. 803, North Tower, Cathedral Heights Building Complex, St. Luke's Medical Center, E. Rodriguez Sr. Ave., Quezon City, 1102 Philippines Telephone No: local 5803 Telefax: Website: Officers 2006 Executive Council President Vice President Secretary Treasurer Immediate Past President Members Divina B. Esteban, MD Alfredo Y. Pontejos, MD Luzviminda S. Kwong, MD Enrico D. Tangco, MD Rafael S. Claudio, MD Romulo S. de Villa, MD, PhD Nelia S. Tan-Liu, MD Juanita Lu-Lim, MD Teresita DV Tuazon, MD Gil M. Vicente, MD Society of Gynecologic Oncologists of the Philippine Unit 414 Manila Astral Tower 1330 Taft Avenue corner P. Faura Street, Ermita Manila Telefax No: Website: Officers President Vice President Secretary Treasurer PRO Board of Directors Efren J. Domingo, MD, PhD Rey H. De Los Reyes, MD, MHSA Ma. Cynthia F. Tan, MD Maria Lilibeth L. Sia Su, MD Gil S. Gonzalez, MD Teresita B. Cardenas, MD Elsie R. Dancel, MD Aris Luke I. Dungo, MD Cecilia L. Llave, MD, PhD Manuel S. Manabat, MD Jose B. Moran, MD Mary Christine F. Palma, MD Wilhelmina D. Rivera, MD Executive Board Assistant Jericho Thaddeus P. Luna, MD Philippine Board of Gynecologic Oncology Chairman Members Genara M. Limson, MD Gil S. Gonzalez, MD Cecilia L. Llave, MD, PhD 269

2 CPM 9 TH EDITION Algorithm for the Cervical Cancer Screening Using Papanicolaou Smear & Direct Visual Inspection PAP SMEAR VIA* Age: 3 years after onset of sexual activity NOT indicated after hysterectomy for benign disease - (CIN 2 or 3 are exceptions to these benign conditions) Interval Annual with conventional cytology OR every 2 years with liquid-based cytology. THEN At or after age 30 after 3 consecutive normal smears, may decrease screening interval every 2-3 years ABNORMAL PAP SMEAR Colposcopy + Biopsy + ECC (+)VIA Outright biopsy** Follow Algorithm for Abnormal Pap Smear * VIA = Visual inspection by Acetic Acid ** Acceptable in areas where colposcopy is not available PRE-MALIGNANT Follow Algorithm for Premalignant Lesions Figure 1 IMPORTANT NOTE: The algorithms apply for practitioners with training in colposcopy. For those with no training in colposcopy, please refer to a Gynecologic Oncologist. 270

3 Algorithm for the Management of Abnormal Pap Smear ABNORMAL PAP SMEAR ASCUS LSIL* 2 ASC-H HSIL AGUS* 1 CARCINOMA No gross lesion (+) Gross Lesion HPV Typing if available * 3 Repeat Pap smear after 4-6 months Colposcopy ± biopsy ± ECC BIOPSY NORMAL Abnormal Smear Definitive Treatment (Refer to Gyne-Onco) Pap Smear Colposcopy Ff up q 3-6 months Normal CIN I CIN II CIN III /CIS MIC CA / Invasive CA * 1 For AGUS, if ECC is negative, fractional curettage is recommended. 2 If LSIL was obtained by liquid based cytology, colposcopy is optional 3 A (+) HPV typing would mandate immediate follow up and colposcopy Figure 2 271

4 Algorithm for the Management of Pre-Malignant Lesions CPM 9 TH EDITION COLPOSCOPY ± biopsy ± ECC CIN I CIN II CIN III / CIS Microinvasive CA/ Invasive Carcinoma 1. Observe OR 2. Cryotherapy Pap smear Colposcopy Ff up q 3-6 mos 2 consecutive normal Paps Annual Pap smear 1. Cryotherapy OR 2. Deep electrocautery (7mm) CIN II Desirous of Pregnancy Close ff-up Pap Smear Colposcopy Ffup q 3-6 mos. 2 consecutive normal Paps Conization, Cold Knife Cone Biopsy Or LEEP/LLETZ CIN III / CIS Follow-up Recurrent/Persistent CIN III / CIS TH ± BSO* TH + BSO* Annual Pap smear Microinvasive CA FIGO Clinical Staging Definitive Treatment (Refer to Gyne Onco) Figure 3 *Comments: 1. Must differentiate between (+) and (-) margins after a cone or LEEP According to the 2002 ASCCP Guidelines TH± BSO as primary treatment for biopsy proven CIN 1, 2 or 3 is UNACCEPTABLE. However, in exceptional cases where the following conditions apply TH±BSO may be considered: 1. poor patient follow-up 2. concurrent benign conditions: myoma uteri, PID, ovarian cyst 272

5 The Clinical Practice Guidelines for Cervical Cancer I. INCIDENCE: Age Standardized Rate 20.0/100,000 1 Age Incidence: - PGH and Rizal province between 40 and 60 years old - Same observation nationwide and worldwide - Age specific incidence (Rizal province) between 30 and 35 years old II. RISK FACTORS Multiple sexual partners Early sexual activity Multiparity History of sexually transmitted infection History of such infection in the sexual partner Smoking history - 40 pack years Table I. Relative Risk* of Factors Associated with Cervical Cancer 2 RISK FACTORS relative Risk HIV Very High Moderate Dysplasia on Pap Smear within past 5 years Very High Intercourse within one year of menarche 16 No prior screening 10 HPV (depending on subtype) Six or more lifetime sexual partners 5 Low socioeconomic class 5 Race (black vs. white) 2.5 Smoking 2 Oral contraceptive pill use Barrier contraception 0.5 *DEFINITION: The Relative Risk Factor (RR) of a disease is the ratio of the incidence in people with the risk factor (exposed persons) to the incidence in people without the risk factor (unexposed persons) 3. The farther the RR is from 1.0, the greater the difference in risk between the two groups 4. III. PRIMARY PREVENTION Monogamous sexual relationship between husband and wife Delay in onset of sexual intercourse NOTE: There is a greater than twofold risk of cervical cancer for those starting intercourse at ages years versus those over 20 years 5. Use of barrier contraceptives like condoms (for male and female) and diaphragms Prompt and adequate treatment of sexually transmitted infections HPV Vaccination - for females 9-26 years old, may be given. IV. SECONDARY PREVENTION A. RECOMMENDED SCREENING 6 When to start screening Approximately 3 years after onset of sexual activity When to discontinue screening Age 70 years with an intact cervix plus a history of a 3 consecutive normal smears & no history of abnormal cytology within the 10-year period prior to 70 Note: For high risk patients ( 1 risk factor), annual Pap smear is still recommended even if the ACS guidelines for discontinuation of screening is satisfied. Screening after hysterectomy Not indicated following hysterectomy for benign disease Note: 1. CIN 2/3 are exceptions to these benign conditions and warrant screening even after hysterectomy 2. For post-hysterectomy (for benign disease) high risk patients, annual Pap smear is still recommended to screen for vaginal intra-epithelial neoplasia (VAIN) Screening interval Annual with conventional cytology OR Every 2 years with liquid-based cytology THEN At or after age 30, after 3 consecutive normal smears, may decrease screening interval every 2-3 years Note: 1. For high risk patients ( 1 risk factor), annual Pap smear is recommended. 2. For centers without a cytology unit, annual direct visual inspection (DVI) is recommended. B. CERVICAL CANCER SCREENING USING PAPANICOLAOU SMEAR & DIRECT VISUAL INSPECTION Please refer to Figure 1. V. CLINICAL PRESENTATION A. Early symptoms: 1. Vaginal bleeding - most important symptom a. induced by sexual intercourse or internal examination b. intermenstrual 2. Vaginal discharge B. Late symptoms: 1. bone pain 2. urinary and bowel disturbances 3. leg edema 273

6 VI. DIAGNOSIS A. Minimal requirements for diagnosis 1. cervical punch biopsy for those with grossly evident tumor 2. colposcopy and colpo-guided biopsies following investigation of an abnormal Pap smear 3. pelvic examination including rectovaginal examination B. Optional examinations (but are included in the clinical staging as recommended by FIGO) 1. Blood examinations including CBC, Liver function tests, renal function tests 2. Chest x-ray 3. KUB-IVP 4. Cystoscopy/ proctosigmoidoscopy VII. MANAGEMENT OF ABNORMAL PAP SMEAR 274 Please refer to Figure 2. VIII. MANAGEMENT OF PRE-MALIGNANT LESIONS IX. Stage I Please refer to Figure 3. Stage IA FIGO CLINICAL STAGING FOR CERVI- CAL CANCER (Figure 4) Carcinoma strictly confined to the cervix; extension to the uterine corpus should be disregarded. Invasive cancer identified only microscopically. All gross lesions even with superficial invasion are stage Ib cancers. Invasion is limited to measured stromal invasion with a maximum depth of 5 mm* and no wider than 7 mm. Stage IA1 Measured invasion of the stroma no greater than 3 mm in depth and no wider than 7 mm in diameter Stage IA2 Measured invasion of stroma greater than 3 mm but no greater than 5 mm in depth and no wider than 7 mm in diameter Stage IB Clinical lesions confined to the cervix or preclinical lesions greater than Stage IA. Stage IB1 Clinical lesions no greater than 4 cm in size. Stage IB2 Clinical lesions greater than 4 cm in size * The depth of invasion should not be more than 5 mm taken from the base of the epithelium, either surface or glandular, from which it originates. Vascular space involvement, either venous or lymphatic, should not alter the staging. Stage II CPM 9 TH EDITION Carcinoma that extends beyond the cervix but has not extended onto the pelvic wall. The carcinoma involves the vagina but not as far as the lower third. Stage IIA No obvious parametrial involvement. Involvement of up to the upper two thirds of the vagina. Stage IIB Obvious parametrial involvement, but not onto the pelvic sidewall. Stage III Carcinoma that has extended onto the pelvic sidewall. On rectal examination, there is no cancer free space between the tumor and the pelvic sidewall. The tumor involves the lower third of the vagina. All cases with a hydronephrosis or nonfunctioning kidney should be included, unless they are known to be due to other causes. Stage IIIA No extension onto the pelvic sidewall but involvement of the lower third of the vagina Stage IIIB Extension onto the pelvic sidewall or with hydronephrosis or nonfunctioning kidney Stage IV Carcinoma that has extended beyond the true pelvis or has clinically involved the mucosa of the bladder / or rectum Stage IVA Spread of the tumor onto adjacent pelvic organs Stage IVB Spread to distant organs X. CLASSIFICATION OF CERVICAL TU- MORS 7 A. EPITHELIAL TUMORS (Modified WHO histological classification) 1. Squamous cell carcinoma a. Microinvasive squamous cell carcinoma b. Invasive squamous cell carcinoma 1. Large cell keratinizing 2. Large cell non-keratinizing 3. Small cell type c. Verrucous carcinoma d. Warty (Condylomatous) carcinoma e. Papillary squamous cell (Transitional) carcinoma f. Lymphoepithelioma-like carcinoma 2. Adenocarcinoma a. Mucinous adenocarcinoma 1. endocervical type 2. intestinal type 3. signet-ring type b. endometrioid adenocarcinoma 1. endometrioid adenocarcinoma with squamous

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8 metaplasia c. clear cell adenocarcinoma d. minimal deviation adenocarcinoma e. serous adenocarcinoma f. mesonephric carcinoma g. well-differentiated villoglandular adenocarcinoma 3. Other Epithelial tumors a. adenosquamous carcinoma b. glassy cell carcinoma c. mucoepidermoid carcinoma d. adenoid cystic carcinoma e. adenoid basal carcinoma f. carcinoid-like tumor g. small cell carcinoma h. undifferentiated carcinoma i. clear cell adenosquamous carcinoma B. MESENCHYMAL TUMORS AND MIXED EPITHELIAL- MESENCHYMAL 1. Leiomyosarcoma 2. Endocervical stromal sarcoma 3. Embryonal rhabdomyosarcoma 4. Alveolar soft-part sarcoma 5. Adenosarcoma 6. Malignant mixed mesodermal tumor C. MISCELLANOUS TUMORS 1. Primary malignant melanoma 2. Primary choriocarcinoma 3. Lymphoma 4. Leukemia 5. Primary germ cell tumor XI. MANAGEMENT OF CERVICAL CANCER A. GENERAL GUIDELINES 1. is diagnosed by biopsy. In the presence of a gross lesion, there is no need for a Papanicolaou smear or a fractional curettage. 2. is staged clinically. 3. If clinically indicated, proctosigmoidoscopy and cystoscopy should be done to rule out invasion. 4. Special work-ups may include computed tomography, magnetic resonance imaging, PET scan and bone scan. 5. Once the diagnosis of invasive cancer is made, the patient should be referred to a gynecologic oncologist. 6. In selected cases, primary Radical Hysterectomy with Pelvic Node Dissection must be performed by a gynecologic oncologist. 7. For advanced disease, concurrent chemotherapy and radiotherapy is the minimum standard of treatment. 276 (8,9,10,11,12) CPM 9 TH EDITION 8. Primary total hysterectomy with or without bilateral salpingo-oophorectomy is NOT performed for a patient with cervical cancer. It is an inadequate surgery and would mean cutting through tumor. The prognosis is uniformly poor in this situation. Surgical cure is NOT obtained and the probability of curative radiotherapy is greatly diminished The treatment of cervical cancer requires a multidisciplinary approach involving a gynecologic oncologist and a radiation oncologist. XIII. REFERENCES 1. Esteban DB & Nuqui EA, The Cancer Problem: An Overview. In Nuqui EA: The Philippine Handbook of Clinical Oncology, 2 nd Edition, 2001:4. 2. The National Guideline Clearinghouse Revised Cervical Cancer Screening Recommendations, June Dawson B & Trapp RG, Basic & Clinical Biostatistics, 3 rd Ed, McGraw-Hill Book Co., 2001: Greenberg RS, Daniels SR, Flanders WD, Eley JW & Boring JR III. Medical Epidemiology, 3 rd /ed. The McGraw-Hill Companies, Inc., 2001: Herrero R, Brinton LA, Reeves WC, et al: Sexual behavior, venereal disease, hygiene practices and invasive cervical cancer in a high risk population. Cancer 65: 380, Saslow D, Runowicz CD, Solomon D, Moscicki AB, Smith RA, Eyre HJ, Cohen C: American Cancer Society Guideline for the Early Detection of Cervical Neoplasia and Cancer: CA Cancer J. Clin. 2002; Kurman RJ, Blaustein s Pathology of the Female Genital Tract, 4 th Ed., Springer: Verlag New York, Inc Whitney CW, Sause W, Bundy BN et al. Randomized comparison of 5-Fluorouracil plus Cisplatin versus Hydroxyurea as an adjunct to radiation therapy in Stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: A Gynecologic Oncology Group and Soutwest Oncology Group study. Journal of Clinical Oncology 17: , Rose PG, Bundy BN, Watkins EB et al: Concurrent Cisplatin-based chemotherapy and radiotherapy for locally advanced cervical cancer. New England Journal of Medicine: 340: , Keys HM, Bundy BN, Stehman FB, et al: Cisplatin, radiation and adjuvant hysterectomy for bulky stage Ib cervical carcinoma. New England Journal of Medicine. 340: , Morris M, Eifel PJ, Lu J, et al: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. New England Journal of Medicine. 340: , Peters WAI, Liu PY, Barrett R, et al: Cisplatin, 5-Fluorouracil plus radiation therapy are superior to radiation therapy as adjunctive therapy in high risk, early stage carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: Report of a phase III Intergroup Study. Gynecologic Oncology 72: 443; Lehman M, Thomas G. Is concurrent chemotherapy and radiotherapy the new standard of care for locally advanced cervical cancer? International Journal of Gynecological Cancer. 11, pp Section of Gynecologic Oncology, Philippine General Hospital. Criteria for the Retention of Ovaries in Cervical Cancer, Workshop held last March 7, Wright, TC, Cox JT, Massad S Consensus Guidelines for the Management of Women with Cervical Intraepithelial Neoplasia. Am J of Ob Gyn (Note: Please see appendix for more details re this article).

9 Available Vaccine in the Philippines HPV Vaccine Quadrivalent HPV vaccine Gardasil 277