2. Age-standardized incidence of cervical cancer in selected worldwide countries Zimbabwe, Harare Peru, Trujilo India, Madras Colombia, Cali Argentina India, Bombay New Zealand, Maori Costa Rica Thailand Mali, Bamako Korea,Kangwha US, SEER, Black Canada Denmark Belgium Israel Rate per 100,000 ( IARC, 1996 ) 67.2 53.5 38.9 34.2 32.2 27.7 24.2 24.0 23.2 21.8 12.0 7.8 7.6 4.8 7.5 26.7

3. Cumulative 5 year survival according to clinical stage survival(%) 12% 41% months Stage I Annual Report Gynecological Cancer, 1994 Kim et al., 2003 (Yonsei Univ.) 69% 88% Stage III Stage IV Stage I I 10% 52% Stage I 75% 86% Stage III Stage IV Stage I I months

4. Definition Recurrence after radiation A regrowth of tumor in the pelvis or distally, noted after complete healing of the cervix and vagina have been achieved. The continuous presence of original tumor or the development of a new tumor in the pelvis within 3 months of radiotherapy completion Persistent disease after radiation therapy ( DiSaia et al., 1992 )

5. Definition Recurrence after surgery Evidence of a tumor mass after operation in which all gross tumor was removed and the margins of the specimen were free of disease. Defined as the continuous presence of gross tumor in the operative field. Persistent disease after surgery ( DiSaia et al., 1992 )

6. Incidence of recurrence Year No. of patients 28.7% 26.0% Total number of patients Recurrent cases Kim et al., 2003 (Yonsei Univ.)

7. Incidence of recurrence according to clinical stage 100% Stage No. of patients 0% Total number of patients Recurrent cases 10.7 27.9 47.5 80.0 Kim et al., 2003 (Yonsei Univ.)

8. Colpophotograph of vaginal recurrence Pre-treatmentPost-treatment

9. Classification of Vaginal Recurrence of Cervical Cancer Ito et al, 1997 Vaginal recurrence determined by bimanual rectovaginal examination Small : involving only vaginal surface Medium : recurrent mass less than 3 cm Large : tumor mass exceeds 3 cm or larger extends to the pelvic cavity

10. Ijaz et al, 1998 In a manner of paralleling the FIGO classification of vaginal cancer Group 1 : mucosal involvement only Group 2 : paravaginal extension Group 3 : central recurrence with pelvic side wall extension Group 4 : recurrence limited to the pelvic sidewall Classification of Vaginal Recurrence of Cervical Cancer

11. Management of vaginal recurrence Mode of previous treatment Extent of recurrent disease Patients’ performance status Initial treatment  Surgery : radiation therapy chemoradiotherapy  Radiation : surgical treatment Chemotherapy investigational or palliative

12. Various Radiotherapeutic Approaches Interstitial implant Altered fractionation of radiation Hyperbaric oxygen therapy Hyperthermia / Radiotherapy Intraoperative radiotherapy (IORT) Combined operative and radiotherapeutic treatment (CORT)

13. Patients and Methods 1990-2000, Dept of OB/GYN, Yonsei University College of Medicine 478 Patients with cervical cancer (retrospective review) 131 recurrent cervical cancer (27.4%) Previous treatment modality Surgery : 16 patients Radiation therapy ; 125 patients Vaginal recurrence including pelvic site ; 55 patients Clinicopathologic analysis Management modalities(radiation, chemotherapy, combination) Age, Cell type, Previous treatment modalities, Extent of recurrence,

14. Characteristics Age( years) Median Range FIGO stage at initial diagnosis I II III Histology type Squamous cell carcinoma Adenocarcinoma Adenosquamous carcinoma Previous treatment Radiation CTx + RTx CTx + Surgery Surgery Time to recurrence (months) Median 58 38 - 75 1323 1731 2546 4378 814 4 8 1934 1528 2 3 1935 10.5 Patients No. Percent Patient characteristics

15. Patients No. Percent Extent of recurrence group I group II group III Treatment of recurrent cervical cancer Radiotherapy Chemotherapy Radiotherapy + Chemotherapy Surgery Chemotherapy regimen DDP + Taxol DDP + 5-FU DDP + VCR DDP + ADR Ifosfamide + Carboplatin + Cisplatin Survival month (median) 1222 2444 1934 2036 2443 816 3 5 825 10 31 3 9 2 6 929 21 Characteristics Patient characteristics

16. Surgical approaches Pelvic exenteration - surgical treatment of choice for some patients having centrally recurrent cervical cancer after radiation therapy - exenterative procedures may be partial (conservation of bladder or rectum) or total.

17. Pelvic exenteration Douglas and Sweeney(1957) Parsons and Friedell(1964) Brunschwig(1967) Bricker(1967) Krieger and Embree(1969) Ketcham er al.(1970) Symmonds et al.(1975) Morley and Lindenauer(1976) Rutledge et al.(1977) Averette et al.(1984) Lawhead et al.(1989) Soper et al.(1989) Shingleton et al.(1989) Total 23 112 535 153 35 162 198 34 296 92 65 69 143 1917 (4.3%) (21.4%) (16%) (10%) (11%) (7.4%) (8%) (2.9%) (13.5%) (25%) (9.2%) (7.2%) (6.3%) (12.6%) 5 24 108 53 13 62 64 21 99 34 15 28 71 647 Number of patients treated Number of operative deaths 1 24 86 15 4 12 16 1 40 23 6 5 9 242 Number surviving 5 years (22%) (21.4%) (20.1%) (34.6%) (37%) (38.2%) (32.3%) (62%) (33.4%) (37%) (23%) (40.5%) (50%) (33.8%) Auther

18. Pelvic exenteration Initial stage IB IIA IIB Age 53 43 47 Type post* Status NED DOD Months of follow-up 9 11 6 post*, posterior exenteraion; NED, no evidence of disease; DOD, dead of disease

19. 2(10) 7(33) 6(29) 5(24) 1(5) 21 1(6) 3(19) 9(56) 2(13) 1(6) 16 4(7) 12(22) 25(46) 12(22) 2(4) 55 Age Group(%) IIII Total Age distribution II 1(6) 2(11) 10(56) 5(28) - 18 30-39 40-49 50-59 60-69  70 Total

20. I II III Total Group Clinical stage I II III Total Relationship between primary clinical stage and recurrent group 9 3 1 13 2 3 12 17 10 12 3 25 21 18 16 55

21. Cumulative 5 year survival according to histological cell type months survival(%) p< 0.01 Adenocarcinoma Adenosqumou cell cancer Squamous carcinoma 46% 20% 12% 18% 52% months Adenocarcinoma Squamous carcinoma P= 0.05 Ijaz et al., 1998 Kim et al., 2003 (Yonsei Univ.)

22. Cumulative 5 year survival according to groups months survival(%) p< 0.01 Group III Group II Group I 48% 16% 12% Kim et al., 2003 (Yonsei Univ.)

23. Cumulative 5 year survival according to treatment modalities months survival(%) Chemotherapy Radiotherapy Chemoradiotherapy 16% 12% Kim et al., 2003 (Yonsei Univ.)

24. Conclusions Control of vaginal recurrence of cervical cancer remains beyond the reach of current treatment modalities. Because the benefits of the various therapies are not great, every effort should be made to enroll patients on new trials such as paclitaxel chemotherapy, amiphostine chemoprotection, combined use of retinoic acids, and gene therapy.