Japanese Journal of Clinical Oncology 34:99-103 (2004)
© 2004 Foundation for Promotion of Cancer Research
Postoperative Radiotherapy for Uterine Cervical Cancer: Results of the 1995–1997 Patterns of Care Process Survey in Japan
1 Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Okinawa, 2 Department of Radiology, Tokyo Women’s Medical University, Tokyo, 3 Department of Clinical Radiology, Graduate School of Medical Science, Kyushu University, Fukuoka, 4 Department of Medical Engineering, Osaka University Medical School, Osaka and 5 Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
|---|
Objective: To determine the average national practice of postoperative radiotherapy for uterine cervical cancer in Japan.
Methods: The Japanese Patterns of Care Study (PCS) reviewed the process of care employed for 455 uterine cervical cancer patients who were treated with surgery followed by postoperative radiotherapy (RT) during 1995–1997. Cases with missing data were excluded from calculations of percentage and significance for each of the surveyed items.
Results: According to FIGO stages, 198 patients (45%) were in stage I, 52 patients (12%) were in stage IIA, 146 patients (33%) were in stage IIB and 46 patients (10%) were in stage III/IVA. The most common surgical procedure among the patients was radical hysterectomy (73%). Three hundred and seventy patients (82%) were treated with external beam RT (ERT) alone, and 74 patients (17%) were treated with a combination of ERT and intracavitary RT (ICRT). A midline block was used for the pelvic field in 63 patients (14%). Only seven patients (2%) were treated with extended field ERT. Pelvic ERT was most often performed using AP-PA opposed fields for 431 patients (97%). A majority of the patients (312 patients, 70%) were treated with a total dose of 45.0–50.4 Gy for ERT. Chemotherapy (CT) was administered to 178 patients (40%), neoadjuvant preoperative CT was administered to 80 patients (22%) and concurrent CT with postoperative RT was administered to 29 patients (8%).
Conclusion: This PCS established the national practice average of postoperative RT for uterine cervical cancer. Follow-up studies need to be conducted to determine whether the observed differences in treatment processes affect outcomes.
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
|---|
Although several retrospective studies (1) and one randomized clinical trial (2) have demonstrated that both surgery and radiotherapy produce equivalent cure rates, surgery has been widely chosen as a primary treatment for patients with early stage uterine cervical cancer. Postoperative adjuvant radiotherapy (RT) has been administered to selected patients with unfavorable histopathologic findings in their surgical specimens.
The Patterns of Care Study (PCS) has conducted a national survey to measure the structure, process and outcome for patients with uterine cervical cancer, who were treated with radical RT (non-surgery) since 1974 in the US. Several important findings of the process and outcomes have been demonstrated from the US PCS surveys (3–5). However, the US PCS excluded patients who were treated with surgery and postoperative RT. Although numerous data from retrospective studies were available, national practice standards of postoperative RT for uterine cervical cancer have not been systemically reviewed either in the US or in Japan.
A Japanese PCS working group initiated a nationwide survey of four major types of cancers (cervix, esophagus, lung and breast) in 1998. Patients treated with surgery prior to RT were also eligible for the Japanese PCS survey. Therefore, we were able to collect the data regarding surgically treated patients with uterine cervical cancer.
The purpose of this study is to determine the national practice average of postoperative RT for uterine cervical cancer in Japan.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
|---|
The Japanese PCS working group carried out an extramural survey of institutions for radiation treatment from September 1998 to March 2001. This group developed an original data format for patients with uterine cervical cancer. Of the total 556 institutions, 73 were selected for the survey by a stratified two-staged cluster sampling method. The data collection method comprised of two steps of random sampling. Prior to the random sampling, all the institutions were classified into four groups. The Japanese PCS classified the Japanese institutions as follows (6): (a) A1—academic institutions, cancer centers/university hospitals treating
300 patients/year, (b) A2—academic institutions, cancer centers/university hospitals treating <300 patients/year, (c) B1—non-academic institutions and other national, prefectural, municipal or private hospitals treating 120 patients/year and (d) B2—non-academic institutions and other national, prefectural, municipal or private hospitals treating <120 patients/year. In the first step, the institutes were randomly selected from each group. In the second step, eligible patients were randomly selected from each of the sampled institutions. For the following analyses, the four institutional classifications listed above were combined into two groups, namely, A institutions and B institutions. The eligibility criteria of the Japanese PCS for inclusion in the uterine cervical cancer study were as follows: (a) Patients with carcinoma, (b) patients treated from 1995 to 1997, (c) patients without distant metastases, (d) patients without prior or concurrent malignancies, (e) patients without gross para-aortic lymph node metastases and (f) patients who had not received previous pelvic irradiation.
The Japanese PCS collected clinical data on 1065 patients with uterine cervical cancer, who were treated with RT between 1995 and 1997. Data from 455 of these patients who were treated with surgery and postoperative RT were subjected to the following analyses. The Japanese PCS surveyors comprised 20 radiation oncologists from 10 academic institutions. One radiation oncologist visited and surveyed the data by reviewing the patients’ charts for each of the institutions.
The data of past history, pretreatment work-up and treatment were collected. The following parameters were evaluated for the past history: previous minor/major abdominopelvic surgery, pulmonary disease, cardiovascular disease, diabetes, collagen vascular disease, inflammatory bowel disease, HIV status and PID. Pretreatment work-up included the following: Karnofsky performance status, height, weight, hemoglobin value, transfusion, histology, tumor markers (SCC and CEA), clinical FIGO stages, diameter of tumor assessed by MRI (T2WI) and nodal status assessed by CT/MRI. Treatments were surveyed for each modality such as surgery, radiotherapy and chemotherapy. Regarding surgery, the type of surgery, number of resected lymph nodes and pathological data of surgical specimens were evaluated. Pathological findings surveyed were as follows: surgical margin status, tumor size (longest and shortest diameters), lymphovascular space involvement, depth of stromal invasion, pathological T stage, pathological N stage and number of metastatic lymph nodes. Details of the treatment method of RT were evaluated. Parameters for external beam RT (ERT) included the following: method of simulation, utilization of midline block, photon energy, technique (i.e. anteroposterior opposed fields and four-field), treatment volume, total dose, daily dose and unplanned treatment breaks. Parameters for intracavitary brachytherapy were as follows: applicator type, radionuclide, sedation, total dose, daily dose and dose-rate. Application of an approved investigational protocol was also surveyed.
Statistical significance was tested by the chi-square test. Cases with unknown values were included; however, cases with missing values were not included in calculations of percentage and significance.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
|---|
A institutions included 202 patients (A1: 168, A2: 134) and B institutions included 153 patients (B1: 101, B2: 52).
Table 1 shows the patient characteristics. Of the total 455 patients, 80 patients (18%) were below the age of 40 years and 44 patients (10%) were above the age of 70 years. The median height of the patients was 153 cm, with a range of 130–170 cm (n = 299), and their median weight was 52 kg, with a range of 34–100 kg (n = 313). The Karnofsky performance status (KPS) of A institutions was significantly better than that of B institutions. According to the FIGO classification, 43% of the patients had stage IIB disease or greater (IIB, IIIA/B and IVA).
|
Table 2 shows the types of surgical procedures employed. The most common surgical procedure was radical hysterectomy, and this was followed by extended radical hysterectomy. Radical hysterectomy was performed more frequently in A institutions than in B institutions. The median number of resected lymph nodes was 19, with a range of 0–90 (n = 207).
|
Table 3 shows the pathological findings of surgical specimens. Although the availability of data regarding surgical margin status and pelvic nodal status was high, about half of the cases for stromal invasion and lymphovascular space involvement were missing. The pathological tumor diameter was recorded for only 121 patients (27%).
|
Table 4 shows parameters of RT. A majority of the patients were treated with ERT alone. Intracavitary RT (ICRT) to the vaginal cuff was performed for 80 patients (18%). ICRT was utilized more frequently in A institutions than in B institutions. Utilization rates for ICRT were 38% (29/76) for patients with positive surgical margins and 11% (36/329) for those with negative surgical margins. A midline block was used for the pelvic field in 63 patients (14%). No significant difference was observed in the utilization of midline block between A institutions and B institutions. Utilization rates of midline block were 75% (53/70) for patients treated with ICRT and 3% (10/370) for those with no ICRT. Machine energies used in A institutions were significantly higher than those used in B institutions. Most patients received only whole-pelvis treatment with ERT. Only seven patients (2%) were treated with extended fields that included the para-aortic region. Pelvic ERT was most often administered with anterior and posterior opposed fields. Only 12 patients (2%) were treated with a four-field technique. The median total dose of pelvic ERT was 50 Gy. Three hundred and twelve patients (70%) were treated with a total dose of 45.0–50.4 Gy. The most commonly used daily dose of ERT was 1.8 Gy (52%), this was followed by 2.0 Gy (41%).
|
The median interval from surgery to the start of RT was 28 days, with a range of 8–230 days (n = 445). The median overall treatment time from initiation of RT to completion was 39 days, with a range of 1–120 days. Four hundred and thirty patients (95%) completed the planned treatment.
Chemotherapy was administered to 178 patients (40%). Of these, 118 patients (68%) received chemotherapy including platinum agents. Preoperative neoadjuvant chemotherapy (NAC) was administered to 80 patients (22%), and concurrent chemotherapy with postoperative RT was administered to 29 patients (8%). The utilization rate of NAC was significantly higher in A institutions than in B institutions (P = 0.004). Only five patients (1%) were treated with an investigational protocol.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
|---|
The incidence of adenocarcinoma was high in the postoperative RT group as compared to the non-surgery group (7). This might indicate that patients with cervical adenocarcinoma tend to receive surgical treatment, because most gynecologic oncologists consider adenocarcinomas to be radioresistant. Several investigators have shown that the control of pelvic adenocarcinomas is comparable with that of squamous cell carcinomas, when treatment consisted of radical radiotherapy (8,9). However, the present data suggests that this was not accepted in clinical practice in Japan. Regarding the clinical stages, locally advanced cases (FIGO stage
IIB) were frequently included in this series. This might indicate that a significant number of patients with inoperable stage cancer underwent surgery, probably after NAC in Japan. Various pathologic risk factors with regard to surgically treated early stage uterine cervical cancer have been identified (10). The availability of data describing these pathologic findings was unsatisfactory, except for the surgical margin status and pelvic nodal status in this survey. This suggested that indications for postoperative RT were determined primarily by the surgical margin and pathological nodal status in Japan. However, we could not directly analyze the indications for postoperative RT in each patient because of the inadequacy of the data format. In the next survey, these data will be available in a revised format.
Several interesting findings were observed with respect to radiation parameters. Although no studies have shown significant therapeutic value of ICRT to the vaginal cuff, 15% of the patients were treated with ICRT. Patients with a positive surgical margin in the vaginal cuff might be considered as candidates for an ICRT boost. However, according to Kim et al. some uncertainties are associated with the dose distribution of the ICRT boost (11). On the other hand, 9% of the patients with negative surgical margins also underwent an ICRT boost. Similarly, indications for a midline block were also unclear. A midline block was utilized not only for patients treated with ICRT but also for those who did not receive ICRT. Both, the efficacy and indications for ICRT boost and midline block should be further explored. Although a published randomized study of the Radiation Therapy Oncology Group (RTOG) showed positive results for prophylactic extended-field RT to the para-aortic region in 1995 (12), this finding was not incorporated in the clinical practice in the intervening time period. Regarding the technique of ERT, almost all patients were treated with the AP-PA opposed fields in this series. In the US PCS, data showed that 70% of the patients were treated with the four-field technique (5). Higher energy was used in the USA than in Japan. The most frequently used X-ray beam energies were 15 MV in the USA (5) and 10–14 MV in Japan. From these data, one might consider the technique of ERT practiced in Japan to be inappropriate to obtain an accurate dose distribution in both clinical target volume (CTV) and the surrounding normal organs. However, this finding should be interpreted carefully. An estimation of body size, i.e., AP separation, would be necessary to evaluate the most appropriate method and energy of ERT. The AP separation of Japanese women might be less than that of women in the USA. We consider that the four-field technique should be applied only if a machine with low-beam energy is available.
Although the efficacy of preoperative NAC was not fully determined by phase III trials within this study period, about one fifth of the patients were treated with NAC in this series. NAC was administered not only for operable stage IB patients but also for patients with more advanced, inoperable stages. Almost all of these patients were treated outside an investigational protocol. Patients in academic institutions were more frequently treated with NAC than those in non-academic institutions. This might indicate that Japanese academic institutions tend to apply new treatment strategies regardless of proven therapeutic evidence. One randomized trial from Argentina demonstrated the positive value of NAC prior to surgery for stage IB uterine cervical cancer in 1997 (14). We suspect that utilization of NAC will become more frequent in the next time period that will be studied. Concurrent chemotherapy with postoperative RT was not widely accepted during the periods in this study. In 2000, a randomized intergroup trial demonstrated a positive impact on prognosis in the case of cisplatin-based chemotherapy administered concurrently with postoperative RT to high-risk early-stage uterine cervical cancer patients (15). Therefore, we suspect that this approach will also be incorporated in the daily clinical practices for uterine cervical cancer patients.
To summarize, this study demonstrates the Japanese national practice average of postoperative RT for uterine cervical cancer during 1995–1997. Follow-up studies will be essential to determine the manner in which the observed differences in process affect treatment outcomes.
|
Acknowledgments |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
|---|
This study was supported by a Grant-in-Aid for Cancer Research (Nos 10–17 and 14–6) from the Ministry of Health, Labor and Welfare, Japan and by a Grant from the Japan Society for the Promotion of Sciences. The authors thank all the radiation oncologists and staff who participated in this study. Their cooperation in providing information made these surveys possible.
This paper was presented in part at the 87th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA), Chicago, IL, November 2001, and at the 1st USA/Japan PCS Workshop, San Francisco, CA, November 2001.
|
FOOTNOTES |
|---|
+ For reprints and all correspondence: Takafumi Toita, Department of Radiology, University of the Ryukyus School of Medicine, 207 Uehara, Nishihara-cho, Okinawa 903–0215, Japan. E-mail: b983255{at}med.u-ryukyu.ac.jp
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONAcknowledgmentsREFERENCES |
|---|
1 Perez CA. Uterine cervix. In: Perez CA and Brady LW, editors. Principles and practice of radiation oncology. 3rd ed. Philadelphia: Lippincott-Raven, 1998;1733–834.
2 Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, et al. Randomized study of radical surgery versus radiotherapy for stage Ib–IIa cervical cancer. Lancet 1997;350:535–40.[CrossRef][Web of Science][Medline]
3 Lanciano RM, Pajak TF, Martz K, Hanks GE. The influence of treatment time on outcome for squamous cell cancer of the uterine cervix treated with radiation: a Patterns of Care Study. Int J Radiat Oncol Biol Phys 1993;25:391–7.[Medline]
4 Komaki R, Brickner TJ, Hanlon AL, Owen JB, Hanks GE. Long-term results of treatment of cervical carcinoma in the United States in 1973, 1978 and 1983: Patterns of Care Study (PCS). Int J Radiat Oncol Biol Phys 1995;31:973–82.[Medline]
5 Eifel PJ, Moughan J, Owen J, Katz A, Mahon I, Hanks GE. Patterns of radiotherapy practice for patients with squamous carcinoma of the uterine cervix: Patterns of Care Study. Int J Radiat Oncol Biol Phys 1999;43:351–8.[CrossRef][Medline]
6 Teshima T, Abe M, Ikeda H, Hanks GE, Owen JB, Hiraoka M, et al. Patterns of Care Study for esophagus cancer in Japan: the influence of the stratification of institution on the process. Jpn J Clin Oncol 1998;28:308–13.
7 Maebayashi K, Mitsuhashi N, Toita T, Ogawa K, Teshima T, Takahashi Y, et al. The Patterns of Care Study for cancer of the uterine cervix in Japan: effects of dose rate on outcome. Int J Radiat Oncol Biol Phys 2001;51:S335.
8 Grigsby PW, Perez CA, Kuske RR, Camel HM, Kao MS, Galakatos AE, et al. Adenocarcinoma of the uterine cervix: lack of evidence for a poor prognosis. Radiother Oncol 1988;12:289–96.[CrossRef][Web of Science][Medline]
9 Eifel PJ, Morris M, Oswald MJ, Wharton JT, Delclos L. Adenocarcinoma of the cervix. Prognosis and patterns of failure in 367 cases. Cancer 1990;65:2507–14.[CrossRef][Web of Science][Medline]
10 Koh WJ, Panwala K, Geer B. Adjuvant therapy for high-risk, early stage cervical cancer. Semin Radiat Oncol 2000;10:51–60.[Medline]
11 Kim RY, Salter MM, Shingleton HM. Adjuvant postoperative radiation therapy following radical hysterectomy in stage IB CA of the cervix—analysis of treatment failure. Int J Radiat Oncol Biol Phys 1988;14:445–9.[Medline]
12 Rotman M, Pajak TF, Choi K, Clery M, Marcial V, Grigsby PW, et al. Prophylactic extended-field irradiation of para-aortic lymph nodes in stages IIB and bulky IB and IIA cervical carcinomas: ten-year treatment results of RTOG 79–20. JAMA 1995;274:387–93.
13 Greer BE, Koh WJ, Figge DC, Russell AH, Cain JM, Tamimi HK. Gynecologic radiotherapy fields defined by intraoperative measurements. Gynecol Oncol 1990;38:421–4.[Medline]
14 Sardi JE, Giaroli A, Sananes C, Ferreira M, Soderini A, Bermudez A, et al. Long term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage IB squamous carcinoma of the cervix: the final results. Gynecol Oncol 1997;67:61–9.[CrossRef][Web of Science][Medline]
15 Peters III WA, Liu PY, Barrett II RJ, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000;18:1606–13.
Received September 30, 2003; accepted December 18, 2003
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Teshima and Japanese PCS Working Group Patterns of Care Study in Japan Jpn. J. Clin. Oncol., September 1, 2005; 35(9): 497 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Toita, K. Nakamura, T. Uno, T. Kodaira, A. Shinoda, K. Ogawa, N. Mitsuhashi, K. Maebayashi, A. Kawaguchi, T. Inoue, et al. Radiotherapy for Uterine Cervical Cancer: Results of the 1995-1997 Patterns of Care Process Survey in Japan Jpn. J. Clin. Oncol., March 1, 2005; 35(3): 139 - 148. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||