Adjuvant Postoperative Radiation Therapy for Carcinoma of the Uterine Cervix

자궁경부암의 수술 후 방사선치료

  • Lee Kyung-Ja (Departments of Radiation Oncology College of Medicine, Ewha Womans University) ;
  • Moon Hye Seong (Obstetrics and Gynecology, College of Medicine, Ewha Womans University) ;
  • Kim Seung Cheol (Obstetrics and Gynecology, College of Medicine, Ewha Womans University) ;
  • Kim Chong Il (Obstetrics and Gynecology, College of Medicine, Ewha Womans University) ;
  • Ahn Jung Ja (Obstetrics and Gynecology, College of Medicine, Ewha Womans University)
  • 이경자 (이화여자대학교 의과대학 방사선종양학교실) ;
  • 문혜성 (이화여자대학교 의과대학 산부인과학교실) ;
  • 김승철 (이화여자대학교 의과대학 산부인과학교실) ;
  • 김종일 (이화여자대학교 의과대학 산부인과학교실) ;
  • 안정자 (이화여자대학교 의과대학 산부인과학교실)
  • Published : 2003.09.01

Abstract

Purpose: This study was undertaken to evaluate the efficacy of postoperative radiotherapy, and to investigate the prognostic factors for FIGO stages IB-IIB cervical cancer patients who were treated with simple hysterectomy, or who had high-risk factors following radical hysterectomy and pelvic lymph node dissection. Materials and Methods: Between March 1986 and December 1998, 58 patients, with FIGO stages IB-IIB cervical cancer were included in this study. The indications for postoperative radiation therapy were based on the pathological findings, including lymph node metastasis, positive surgical margin, parametrial extension, lymphovascular invasion, invasion of more than half the cervical stroma, uterine extension and the incidental finding of cervix cancer fellowing simple hysterectomy. All patients received external pelvic radiotherapy, and 5 patients, received an additional intracavitary radiation therapy. The radiation dose from the external beam to the whole pelvis was $40\~50$ Gy. Vagina cuff Irradiation was peformed, after completion of the external beam irradiation, at a low-dose rate of Cs-137, with the total dose of $4488\~4932$ chy (median: 4500 chy) at 5 mm depth from the vagina surface. The median follow-up period was 44 months ($15\~108$ months). Results: The 5-yr actuarial local control rate, distant free survival and disease-free survival rate were $98\%,\;95\%\;and\;94\%$, respectively. A univariate analysis of the clinical and pathological parameters revealed that the clinical stage (p=0.0145), status of vaginal resection margin (p=0.0002) and parametrial extension (p=0.0001) affected the disease-free survival. From a multivariate analysis, only a parametrial extension independently influenced the disease-free survival. Five patients ($9\%$) experienced Grade 2 late treatment-related complications, such as radiation proctitis (1 patient), cystitis (3 patients) and lymphedema of the leg (1 patient). No patient had grade 3 or 4 complications. Conclusion: Our results indicate that postoperative radiation therapy can achieve good local control and survival rates for patients with stages IB-IIB cervical cancer, treated with a simple hysterectomy, as well as for those treated with a radical hysterectomy, and with unfavorable pathological findings. The prognostic factor for disease-free survival was invasion of the parametrium. The prognosic factor identified in this study for treatment failure can be used as a selection criterion for the combined treatment of radiation and che motherapy.

목적: 자궁경부암에서 수술 후 위험인자가 있는 환자에 방사선치료 후 생존율, 국소 제어율과 예후인자를 후향적으로 분석하여 수술 후 방사선치료의 효과를 알고자 한다. 대상 및 방법: 1986년 3월부터 1998년 12월까지 자궁경부암 FIGO 병기 IB-IIB로 자궁적출술 후 방사선치료를 받은 58명을 대상으로 국소 제어율, 5년 무병생존율과 생존율에 미치는 예후인자를 후향적으로 분석하였다. 수술 후 방사선치료의 적응증은 병리학적으로 림프절에 전이된 경우, 암이 수술절제연이나, 자궁주위조직 혹은 자궁체부에 침범하였거나, 림프혈관강에 침범된 경우, 자궁기질의 1/2 이상 깊이 침윤된 경우와 단순 자궁적출술 후 암으로 진단받은 환자로 하였다. 수술 후 방사선치료는 모든 환자에서 골반강에 외부조사를 시행하였으며 5명은 외부조사와 강내조사를 병용하였다. 외부조사는 6 MV x-선을 이용하여 매일 180 cGy를 4문으로 조사하였으며 총 방사선량은 $4400\~5040$ cGy (중앙값: 5040 cGy)이었다. 강내조사는 외부조사 후 2주에 Cs-137를 이용하여 저선량률로 질 표면에서 5 mm 깊이에 $4488\~4932$ cGy (중앙값: 4500 cGy)를 시행하였다. 추적기간은 15개월에서 108개월로 중앙값은 44개월 이었다. 결과: 전체환자의 5년 무병생존율은 $94\%$, 국소 제어율은 $98\%$,이었으며 원격 전이율은 $5\%$이었다. 병기에 따른 5년 무병생존율은 $IB\;97.1\%,\;IIA\;100\%,\;IIB\;68.9\%$(p=0.0145)이었다. 질 절제연에 암의 침범이 없는 경우 5년 무병생존율이 $97.8\%$, 있는 경우 $60\%$, (P=0.0002)이었으며, 자궁주위조직에 암이 침범이 없는 경우의 5년 무병 생존율은 $97.8\%$이었고, 있는 경우는 $33.3\%$이었다(p=0.0001). 다변량 분석에 의하면 자궁주위조직의 침범만이 통계학적으로 의의있는 예후인자이었다. 치료 후 만성합병증은 3명($5\%$,)에서 RTOG grade 2의 방광염, 1명에서 grade 2의 직장염과 1명에서 하지에 림프부종이 나타났다. 결론: 조기 자궁경부암 환자에 단순 자궁적출술을 시행하였거나, 근치적 자궁적출술 후 병리학적으로 재발 위험 인자가 있는 환자에 수술 후 방사선치료를 시행하여 심각한 부작용 없이 비교적 높은 국소 제어율과 생존율을 얻을 수 있었다. 생존율에 영향을 미치는 예후인자는 병리학적으로 암이 자궁주위조직에 침범된 것으로 예후가 불량하였다. 수술 후 방사선치료의 실패원인과 예후인자를 분석한 본 후향적 연구결과를 토대로 앞으로 방사선치료와 항암화학요법을 병용하여 보다 적극적이고 전향적인 연구를 시도하는데 이정표로 이용할 수 있다고 생각한다.

Keywords

References

  1. Delgado G, Bundy B, Zaino R, Sevin B, Creasman WT, Major F. Prospective surgical-pathological study of disease free interval in patients with stage IB squamous cell carcinoma of the cervix: A Gynecologic Oncology Group study. Gynecol Oncol 1990;38:352-357 https://doi.org/10.1016/0090-8258(90)90072-S
  2. Fiorica JV, Roberts WS, Greenberg H, Hoffman MS, LaPolla JP, Cavanagh D. Morbidity and survival patterns in patients after radical hysterectomy and postoperative adjuvant pelvic radiotherapy. Gynecol Oncol 1990;36:343- 347 https://doi.org/10.1016/0090-8258(90)90139-C
  3. Fuller JrAF, Elliot N, Kosloff C, Hoskins WJ, Lewis JL. Determinants of increased risk for recurrence in patients undergoing radical hysterectomy for stage IB & IIA carcinoma of the cervix. Gynecol Oncol 1989;33:34-39 https://doi.org/10.1016/0090-8258(89)90598-2
  4. Tsai CS, Lai CH, Wang CC, et al. The prognostic factors for patients with early cervical cancer treated by radical hysterectomy and postoperative radiotherapy. Gynecol Oncol 1999;75:328- 333 https://doi.org/10.1006/gyno.1999.5527
  5. Hart K, Han I, Deppe G, et al. Postoperative radiation for cervical cancer with pathologic risk factors. Int J Radiat Oncol Biol Phys 1997;37:833-838 https://doi.org/10.1016/S0360-3016(96)00560-3
  6. Russel A, Tong DY, Figge DC, Tamimi HK, Geer BE, Elder SJ. Adjuvant postoperative radiation therapy for carcinoma of the uterine cervix: Patterns of cancer recurrence in patients undergoing elective radiation following radical hysterectomy and pelvic lymphadenectomy. Int J Radiat Oncol Biol Phys 1984;10:211-214 https://doi.org/10.1016/0360-3016(84)90005-1
  7. Krebs HB, Helmkemp BF, Sevin BU. Recurrent cancer of the cervix following radical hysterectomy and pelvic lymph node dissection. Obstet Gynecol 1982;59:422-427
  8. Morgan S, Nelson JH Jr. Surgical treatment of early cervical cancer. Sem Oncol 1982;9:312-332
  9. Michalas S, Rodolakis A, Voulgaris Z, Vlachos G, Giannakoulis N, Diakomanolis E. Management of early- stage cervical carcinoma by modified(type II) radical hysterectomy. Gynecol Oncol 2002;85:415-422 https://doi.org/10.1006/gyno.2002.6633
  10. Burghardt E, Pickel H, Haas J, Lahousen M. Prognostic factors and operative treatment of stage Ib to IIb cervical cancer. Am J Obstet Gynecol 1987;156:988-996 https://doi.org/10.1016/0002-9378(87)90374-7
  11. Samlal RAK, van der Velden J, Ten Kate FJWT, Schilthuis MS, Hart AAM, Lammes FB. Surgical pathologic factors that predict recurrence in stage IB and IIA cervical carcinoma patients with negative pelvic lymph nodes. Cancer 1997;80:1234-1240 https://doi.org/10.1002/(SICI)1097-0142(19971001)80:7<1234::AID-CNCR6>3.0.CO;2-K
  12. Hopkins MP, Morley G. Stage IB squamous cell carcinoma of the cervix: Clinicopathologic factors related to survial. Am J Obstet Gynecol 1991;164:1520-1529 https://doi.org/10.1016/0002-9378(91)91431-U
  13. Berman ML, Bergen S, Salazar H. Influence of histologic features and treatment on the prognosis of patients with cervical cancer metastasis to pelvic lymph node. Gynecol Oncol 1990;39:127-131 https://doi.org/10.1016/0090-8258(90)90418-K
  14. Fuller AF Jr, Elliot N, Kosloff C. Lymph node metastasis from carcinoma of the cervix, Stages IB and IIA: Implication for prognosis and treatment. Gynecol Oncol 1982;13:165-174 https://doi.org/10.1016/0090-8258(82)90024-5
  15. Shingleton HM, Gore H, Soong SJ, et al. Tumor recurrence and survival in stage IB cancer of the cervix. Am J Clin Oncol 1993;6:265-269 https://doi.org/10.1097/00000421-198306000-00002
  16. Snijder-Keilholz A, Hellebrekers BWJ, Zwinderman AH, Von de Vijver MJ, Trimbos JB. Adjuvant radiotherapy following radical hysterectomy for patients with ealy- stage cervical carcinoma (1984-1996). Radiother Oncol 1999;51:161-167 https://doi.org/10.1016/S0167-8140(99)00056-0
  17. Gauthier P, Gore IRA, Shingleton HM, Soong SJ, ORR JW, Hatch KD. Idenfitication of histologic risk groups in stage IB squamous cell carcinoma of the cervix. Obstet Gynecol 1985;66:569-574
  18. Kristensen GB, Abeler VM, Risberg B, Trope C, Bryne M. Tumor size, depth of invasion, and grading of the invasive invasive tumor front are the main prognostic factor in early squamous cell cervical carcinoma. Gynecol Oncol 1999;74: 245-251 https://doi.org/10.1006/gyno.1999.5420
  19. Kim RY, Salter MM, Shingleton HM. Adjuvant postoperative radiation therapy following radical hysterectomy in stage IB carcinoma of the cervix-Analysis of treatment failure. Int J Radiat Oncol Biol Phys 1988;14:445-449 https://doi.org/10.1016/0360-3016(88)90258-1
  20. Gonzlez DG, Ketting BW, van Bunningen B, van Dijk JDP. Carcinoma of the uterine cervix stage IB and IIA: Results of postoperative irradiation in patients with microscopic infiltration in the parametrium and/or lymph node metastasis. Int J Radiat Oncol Biol Phys 1989;16:389-395 https://doi.org/10.1016/0360-3016(89)90335-0
  21. Boyce JG, Fruchter RG, Nicasfri AP. Prognostic factors in stage I carcinoma of the cervix cancer. Cancer 1984;53: 1175-1180 https://doi.org/10.1002/1097-0142(19840301)53:5<1175::AID-CNCR2820530524>3.0.CO;2-Y
  22. Hsu JC, Leung SW, Huang EY, et al. Impact of the extent of parametrial involvement in patients with carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1998;40:405-410 https://doi.org/10.1016/S0360-3016(97)00766-9
  23. Stock RG, Chen ASJ, Flickinger JC, Kalnicki S, Seski J. Node-positive cervical cancer: Impact of pelvic irradiation and patterns of failure. Int J Radiat Oncol Biol Phys 1995; 31:31-36 https://doi.org/10.1016/0360-3016(94)00391-W
  24. Soisson AP, Soper JT, Clarke-Pearson DL, Berchuck A. Montana G, Creasman WT. Adjuvant radiation following radical hysterectomy for patients with stage IB & IIA cervical cancer. Gynecol Oncol 1990;37:390-395 https://doi.org/10.1016/0090-8258(90)90374-T
  25. Wang CJ, Lai CH, Huang HJ, et al. Recurrent cervical carcinoma after primary radical surgery. Am J Obstet Gynecol 1999;181:518-524 https://doi.org/10.1016/S0002-9378(99)70486-2
  26. Monk BJ, Cha DS, Walker JL, et al. Extent of disease as an indication for pelvic radiation following radical hysterectomy and bilateral lymph node dissection in the treatment of stage IB & IIA cervical carcinoma. Gynecol Oncol 1994;54:4-9 https://doi.org/10.1006/gyno.1994.1157
  27. Reny JC, Dimaio T, Fruchter RG, et al. Adjuvant radiation after radical hysterectomy in stage IB squamous cell carcinoma of the cervix. Gynecol Oncol 1990;38:161-165 https://doi.org/10.1016/0090-8258(90)90033-H
  28. Alvarez RD, Soong SJ, Kinney WK, et al. Identification of prognostic factors and risk group in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix. Gynecol Oncol 1989;35:130-135 https://doi.org/10.1016/0090-8258(89)90029-2
  29. Ampil F, Dutta R, Palta S. Elective postoperative external radiotherapy after hysterectomy in early stage carcinoma of the cervix. Cancer 1987;60:280-288 https://doi.org/10.1002/1097-0142(19870801)60:3<280::AID-CNCR2820600303>3.0.CO;2-1
  30. Sedlis A, Bundy BN, Rotman AZ, et al. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group study. Gynecol Oncol 1999;73:177- 183 https://doi.org/10.1006/gyno.1999.5387
  31. Lai CH, Hong JH, Hsueh S, et al. Preoperative prognostic variables and the impact of postoperative adjuvant radiotherapy on the outcomes of Stage IB or II cervical carcinoma patients with or without pelvic lymph node metastasis: An analysis of 891 cases. Cancer 1999;85:1537-1546 https://doi.org/10.1002/(SICI)1097-0142(19990401)85:7<1537::AID-CNCR15>3.0.CO;2-6
  32. Atkovar G, Uzel O, Ozsahin M, et al. Postoperative radiotherapy in carcinoma of the cervix: treatment results and prognostic factors. Radiother Oncol 1995;35:198-205 https://doi.org/10.1016/0167-8140(95)01570-7
  33. Peters WA, Liu PY, Barrett R, et al. Concurrent chemotherapy and pelvic radiation therapy compared withPeters WA, Liu PY, Barrett R, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000;18:1606-1613 https://doi.org/10.1200/JCO.2000.18.8.1606
  34. Delgado G. Stage Ib sqaumous cancer of the cervix: The choice of treatment. Obstet Gynecol Surg 1978;33:134-183
  35. Hsu C, Cheng S, Su S. Prognostics of uterine cervical cancer with extensive lymph node metastasis: Special emphasis on the value of pelvic lymphadenectomy in surgical treatment of uterine cervical cancer. Am J Obstet Gynecol 1972;114:954-962 https://doi.org/10.1016/0002-9378(72)90105-6
  36. Hogan WM, Littmann P, Griner L, Miller CL, Mikuta JJ. Results of radiation therapy given after radical hysterectomy. Cancer 1982;49:1278-1285 https://doi.org/10.1002/1097-0142(19820315)49:6<1278::AID-CNCR2820490634>3.0.CO;2-R
  37. Guttmann R. Significance of postoperative irradiation in carcinoma of the cervix: a ten year survey. Am J Roentgenol 1970;108:1278-1285
  38. Dattoli MJ, Gretz HF III, Beller U, et al. Analysis of multiple prognostic factors in patients with stage IB cervical cancer: Age as a major determinant. Int J Radiat Oncol Biol Phys 1989;17:41-44 https://doi.org/10.1016/0360-3016(89)90368-4