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Influence of omental biopsy on adjuvant treatment field in clinical Stage I endometrial carcinoma
BJOG: an International Journal of Obstetrics and Gynaecology May 2002, Vol. 109, pp. 576– 578
SHORT COMMUNICATION
Influence of omental biopsy on adjuvant treatment field in clinical Stage I endometrial carcinoma Jose J. Nieto, Robert Gornall, Ellen Toms, Suzanne Clarkson, Patrick Hogston, Robert P. Woolas* In this study to assess the role of omental biopsy in the diagnosis of extrapelvic disease, data from 100 consecutive women with clinical Stage I endometrial cancer undergoing primary surgical treatment in our institution were analysed: 80 women had an omental biopsy, 20 did not, and six had adenocarcinoma in the omentum. No obvious morbidity attributable to this rapid and easily performed surgical procedure was recorded. We conclude that visual inspection and palpation of the omentum at the time of abdominal surgery for endometrial carcinoma is worthwhile and advisable. In addition, adopting a protocol of histological assessment upstaged a further two cases of this series. These data suggest that this technique might influence the prescription of adjuvant pelvic radiation in approximately one in 10 women currently considered for such therapy, as disease can be easily documented as having extended beyond the conventional radiotherapy field. Introduction Conventional treatment of endometrial cancer in the United Kingdom is a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Such surgery is curative for the majority of patients but individuals with a recognised high risk of recurrence (e.g. poorly differentiated tumours or greater than 50% myometrial invasion, cervical or adnexal involvement of the tumour) may have subsequent adjuvant pelvic radiotherapy. In 1988 in an attempt to clarify who was truly at high risk of relapse, the FIGO staging system was changed so that it was based on surgico-pathological findings. The contentious issue of ascertainment of pelvic and paraaortic lymph node status1 was introduced. Although it has been demonstrated in tertiary centres that this extended surgical procedure can be carried out with minimum additional morbidity, benefit to the patient remains unproven2. The excision of metastases may be therapeutic, but it is more likely that the role of defining the true extent of disease is the more logical application of additional surgical procedures3. The result of the Medical Research Council ASTEC randomised study may help clarify this issue. However, approximately 50% of women with endometrial cancer are either over the age of 80, morbidly obese or have substantial associated medical
Department of Gynaecological Oncology, St Mary’s Hospital, Portsmouth, UK * Correspondence: Mr R. P. Woolas, Department of Gynaecological Oncology, St Mary’s Hospital, Portsmouth PO3 6AD, UK. D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII: S 1 4 7 0 - 0 3 2 8 ( 0 2 ) 0 1 2 7 2 - 7
problems. In these cases a simple surgical procedure may be more prudent. Histologically endometrial carcinoma is identical to its ovarian counterpart, a disease in which trans-coelomic spread of tumour and an omental deposit are invariably found when the tumour has metastasised. Data from the practice of taking peritoneal washings from women with endometrial carcinoma and series in which complete surgical staging has been undertaken suggest that a proportion of endometrial tumours behave in a similar manner4. It is perhaps pertinent to note that although the simple procedure of taking peritoneal washings is part of the current FIGO staging system, the appropriate management of a patient with positive washings as the only available evidence of extrauterine spread is still contentious and undetermined5. In contrast, demonstrating histological evidence of extrapelvic disease has obvious therapeutic connotations. This study evaluates the role of prospectively examining the omentum at operation in a consecutive series of women undergoing surgery at which an endometrial cancer was diagnosed.
Methods A prospective study was initiated in 1997 whereby all women under the care of the gynaecological oncology service undergoing abdominal hysterectomy for clinical Stage I endometrial carcinoma were also asked to consent for an omental biopsy to be performed. These women were prospectively entered on to a database. In addition, patients attending our combined clinic with a postcode from our www.bjog-elsevier.com
SHORT COMMUNICATION
577
Table 1. Clinical features of six patients with clinical stage I endometrial carcinoma and omental metastases. Cell type Endometrioid Endometrioid Clear cell Serous Endometrioid Endometrioid
Grade 3 3 3 3 2 3
Myo < < > > < >
1=2 1=2 1=2 1=2 1=2 1=2
Adnexa
Lymph nodes
Omentum
Other
ve þve ve ve ve ve
Not done Not done þve þve ve ve
> 1 cm micro >1 cm >1 cm micro macro < 1 cm
þve colon serosa þve washings þve washings pelvic peritoneal bx þve þve sigmoid colon serosa þve washings
catchment area in whom a primary diagnosis of early stage endometrial cancer had been established through hysterectomy were also recruited to this study. These data were analysed when a total of 100 consecutive subjects had been recorded. Patients included in the study undergoing omental biopsy were under the care of two consultants ( P.H. and R.P.W ). In our centre, lymphadenectomy is performed in women who are fit with early endometrial cancer if a poorly differentiated tumour has been identified on histology, intraoperative naked-eye inspection of the uterus appears to suggest greater than 50% depth of myometrium involved or if there is evidence of enlarged lymph nodes at palpation during the surgical procedure. The omental biopsy procedure consisted of a visual inspection of the whole omentum followed by excision of any macroscopic abnormality. If no anomaly was present a representative biopsy was obtained using haemostats and ligature ties.
differentiated, greater than half myometrial penetration, cervical involvement or histopathological presence of extrauterine disease, 49 of the 100 women analysed had one or more of these poor prognostic findings. All six of the women with positive omental disease had at least one of these other high risk features. In addition, 22.7% of women with grade 3 lesions had the omentum involved. There was no mortality or obvious morbidity recorded that could be attributed to the omental biopsy procedure. In all, patients with involved omentum other areas were also affected by the metastatic tumour. However, half of those were small deposits on peritoneal surfaces that might be missed easily, especially when operating in an unfit patient through a small incision. Moreover, omental metastes were found in half of those patients who following selection for a lymphadenectomy were found to have involved nodes.
Discussion Results Eighty patients underwent omental biopsy. The omental biopsy was not performed in 20 patients for several reasons: pre-operative diagnosis of atypical hyperplasia, uterus removed vaginally, unfit patient or lack of informed consent. Ninety-two percent of tumours were of endometrioid type; four were serous, three clear cell and one undifferentiated. Twenty-four percent of cases were well differentiated, 54% moderate and 22% poorly differentiated. Pelvic lymphadenectomy was performed in 27% of cases. 89% of cases underwent peritoneal washings as part of their staging. From the available information 72 cases ( 72%) were surgicopathological Stage I (11 Stage Ia, 38 Stage Ib and 23 Stage Ic); 14 cases were Stage II, eight cases Stage III and six Stage IV. Four cases had adenocarcinoma identified histologically in the pelvic nodes. Two of those cases had tumours in the omentum. Six women (6%) had an omental biopsy which contained adenocarcinoma ( Table 1). Although one of the patients had microscopic ovarian involvement, there was no evidence of macroscopic disease in the ovary of any of the patients. In four of these cases the disease in the omentum was clinically evident. However, in two cases only microscopic disease was present. When high risk features were defined as poorly D RCOG 2002 Br J Obstet Gynaecol 109, pp. 576 – 578
Our cancer centre treats a local population of over 600,000 people. This series contains no referrals from outside this geographic area. In our population, the rate of omental metastases at the time of presentation with apparent early clinical stage endometrial cancer is in the order of 6%. These findings are compatible with those of Chen et al.6 who showed an incidence of 8%. Over half (n ¼ 4) of our cases could be ascertained through direct inspection of the omentum, although one of these four cases had only small miliary nodules which were not obviously metastases at initial appraisal. Around 10% of the high risk patients had omental involvement. This figure went up to 23% when only poorly differentiated malignancies were considered. The presence of histologically confirmed extra pelvic disease places the case in Stage IVb. In such circumstances there is little point in irradiating the pelvis to consolidate loco-regional treatment. Omental biopsy could avoid unnecessary therapy potentially both surgical (lymphadenectomy) and radiotherapy in those patients. Entry to a clinical trial of a systemic therapeutic agent would be more appropriate management. The manner in which staging should be carried out for early endometrial cancer remains controversial. Recent FIGO guidelines suggest total hysterectomy, bilateral
578
SHORT COMMUNICATION
oophorectomy and peritoneal washings through a vertical incision as the minimum required. Pelvic and para-aortic lymphadenectomy may or may not be performed. The Medical Research Council ASTEC study may answer important questions relating to lymphadenectomy when completed. However, pelvic lymphadenectomy even in expert hands is unlikely to be achieved without some morbidity in less fit women. Recognised risk factors associated with endometrial cancer are obesity, cardiovascular disease, diabetes and age. These complications make up to 70% of women with early stage endometrial cancer less fit for general anaesthesia and major surgery and it may be imprudent to conduct staging according to FIGO guidelines. Omental biopsy is unlikely to increase morbidity over hysterectomy alone and could be performed in situations where pelvic lymphadenectomy would entail increased risk for the patient. We conclude that the application of this surgicopathological staging approach in our series has influenced the management of around 15% of our high risk patients
with no obvious detriment to the low risk women who have also undergone an omental biopsy.
References 1. Woolas RP, Oram DH. Current management of endometrial carcinoma. In: Studd J, editor. London: RCOG Press, 1994:181 – 194. 2. Orr Jr JW, Holloway RW, Orr PF, Holimon JL. Surgical staging of uterine cancer: an analysis of perioperative morbidity. Gynecol Oncol 1991;42:209 – 216. 3. Quinn MA. Pelvic lymphadenectomy in high risk endometrial cancer. Int J Gynecol Cancer 1996;6:102 – 107. 4. Kadar N, Homesley HD, Malfetano JH. Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease. Gynecol Oncol 1992;46:145 – 149. 5. Sutton GP. Peritoneal cytology in endometrial carcinoma. Cancer Treat Res 1989;49:41 – 52. 6. Chen SS, Spiegel G. Stage I endometrial carcinoma. Role of omental biopsy and omentectomy. J Reprod Med 1991;36:627 – 629. Accepted 17 December 2001
D RCOG 2002 Br J Obstet Gynaecol 109, pp. 576 – 578
SHORT COMMUNICATION
Influence of omental biopsy on adjuvant treatment field in clinical Stage I endometrial carcinoma Jose J. Nieto, Robert Gornall, Ellen Toms, Suzanne Clarkson, Patrick Hogston, Robert P. Woolas* In this study to assess the role of omental biopsy in the diagnosis of extrapelvic disease, data from 100 consecutive women with clinical Stage I endometrial cancer undergoing primary surgical treatment in our institution were analysed: 80 women had an omental biopsy, 20 did not, and six had adenocarcinoma in the omentum. No obvious morbidity attributable to this rapid and easily performed surgical procedure was recorded. We conclude that visual inspection and palpation of the omentum at the time of abdominal surgery for endometrial carcinoma is worthwhile and advisable. In addition, adopting a protocol of histological assessment upstaged a further two cases of this series. These data suggest that this technique might influence the prescription of adjuvant pelvic radiation in approximately one in 10 women currently considered for such therapy, as disease can be easily documented as having extended beyond the conventional radiotherapy field. Introduction Conventional treatment of endometrial cancer in the United Kingdom is a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Such surgery is curative for the majority of patients but individuals with a recognised high risk of recurrence (e.g. poorly differentiated tumours or greater than 50% myometrial invasion, cervical or adnexal involvement of the tumour) may have subsequent adjuvant pelvic radiotherapy. In 1988 in an attempt to clarify who was truly at high risk of relapse, the FIGO staging system was changed so that it was based on surgico-pathological findings. The contentious issue of ascertainment of pelvic and paraaortic lymph node status1 was introduced. Although it has been demonstrated in tertiary centres that this extended surgical procedure can be carried out with minimum additional morbidity, benefit to the patient remains unproven2. The excision of metastases may be therapeutic, but it is more likely that the role of defining the true extent of disease is the more logical application of additional surgical procedures3. The result of the Medical Research Council ASTEC randomised study may help clarify this issue. However, approximately 50% of women with endometrial cancer are either over the age of 80, morbidly obese or have substantial associated medical
Department of Gynaecological Oncology, St Mary’s Hospital, Portsmouth, UK * Correspondence: Mr R. P. Woolas, Department of Gynaecological Oncology, St Mary’s Hospital, Portsmouth PO3 6AD, UK. D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII: S 1 4 7 0 - 0 3 2 8 ( 0 2 ) 0 1 2 7 2 - 7
problems. In these cases a simple surgical procedure may be more prudent. Histologically endometrial carcinoma is identical to its ovarian counterpart, a disease in which trans-coelomic spread of tumour and an omental deposit are invariably found when the tumour has metastasised. Data from the practice of taking peritoneal washings from women with endometrial carcinoma and series in which complete surgical staging has been undertaken suggest that a proportion of endometrial tumours behave in a similar manner4. It is perhaps pertinent to note that although the simple procedure of taking peritoneal washings is part of the current FIGO staging system, the appropriate management of a patient with positive washings as the only available evidence of extrauterine spread is still contentious and undetermined5. In contrast, demonstrating histological evidence of extrapelvic disease has obvious therapeutic connotations. This study evaluates the role of prospectively examining the omentum at operation in a consecutive series of women undergoing surgery at which an endometrial cancer was diagnosed.
Methods A prospective study was initiated in 1997 whereby all women under the care of the gynaecological oncology service undergoing abdominal hysterectomy for clinical Stage I endometrial carcinoma were also asked to consent for an omental biopsy to be performed. These women were prospectively entered on to a database. In addition, patients attending our combined clinic with a postcode from our www.bjog-elsevier.com
SHORT COMMUNICATION
577
Table 1. Clinical features of six patients with clinical stage I endometrial carcinoma and omental metastases. Cell type Endometrioid Endometrioid Clear cell Serous Endometrioid Endometrioid
Grade 3 3 3 3 2 3
Myo < < > > < >
1=2 1=2 1=2 1=2 1=2 1=2
Adnexa
Lymph nodes
Omentum
Other
ve þve ve ve ve ve
Not done Not done þve þve ve ve
> 1 cm micro >1 cm >1 cm micro macro < 1 cm
þve colon serosa þve washings þve washings pelvic peritoneal bx þve þve sigmoid colon serosa þve washings
catchment area in whom a primary diagnosis of early stage endometrial cancer had been established through hysterectomy were also recruited to this study. These data were analysed when a total of 100 consecutive subjects had been recorded. Patients included in the study undergoing omental biopsy were under the care of two consultants ( P.H. and R.P.W ). In our centre, lymphadenectomy is performed in women who are fit with early endometrial cancer if a poorly differentiated tumour has been identified on histology, intraoperative naked-eye inspection of the uterus appears to suggest greater than 50% depth of myometrium involved or if there is evidence of enlarged lymph nodes at palpation during the surgical procedure. The omental biopsy procedure consisted of a visual inspection of the whole omentum followed by excision of any macroscopic abnormality. If no anomaly was present a representative biopsy was obtained using haemostats and ligature ties.
differentiated, greater than half myometrial penetration, cervical involvement or histopathological presence of extrauterine disease, 49 of the 100 women analysed had one or more of these poor prognostic findings. All six of the women with positive omental disease had at least one of these other high risk features. In addition, 22.7% of women with grade 3 lesions had the omentum involved. There was no mortality or obvious morbidity recorded that could be attributed to the omental biopsy procedure. In all, patients with involved omentum other areas were also affected by the metastatic tumour. However, half of those were small deposits on peritoneal surfaces that might be missed easily, especially when operating in an unfit patient through a small incision. Moreover, omental metastes were found in half of those patients who following selection for a lymphadenectomy were found to have involved nodes.
Discussion Results Eighty patients underwent omental biopsy. The omental biopsy was not performed in 20 patients for several reasons: pre-operative diagnosis of atypical hyperplasia, uterus removed vaginally, unfit patient or lack of informed consent. Ninety-two percent of tumours were of endometrioid type; four were serous, three clear cell and one undifferentiated. Twenty-four percent of cases were well differentiated, 54% moderate and 22% poorly differentiated. Pelvic lymphadenectomy was performed in 27% of cases. 89% of cases underwent peritoneal washings as part of their staging. From the available information 72 cases ( 72%) were surgicopathological Stage I (11 Stage Ia, 38 Stage Ib and 23 Stage Ic); 14 cases were Stage II, eight cases Stage III and six Stage IV. Four cases had adenocarcinoma identified histologically in the pelvic nodes. Two of those cases had tumours in the omentum. Six women (6%) had an omental biopsy which contained adenocarcinoma ( Table 1). Although one of the patients had microscopic ovarian involvement, there was no evidence of macroscopic disease in the ovary of any of the patients. In four of these cases the disease in the omentum was clinically evident. However, in two cases only microscopic disease was present. When high risk features were defined as poorly D RCOG 2002 Br J Obstet Gynaecol 109, pp. 576 – 578
Our cancer centre treats a local population of over 600,000 people. This series contains no referrals from outside this geographic area. In our population, the rate of omental metastases at the time of presentation with apparent early clinical stage endometrial cancer is in the order of 6%. These findings are compatible with those of Chen et al.6 who showed an incidence of 8%. Over half (n ¼ 4) of our cases could be ascertained through direct inspection of the omentum, although one of these four cases had only small miliary nodules which were not obviously metastases at initial appraisal. Around 10% of the high risk patients had omental involvement. This figure went up to 23% when only poorly differentiated malignancies were considered. The presence of histologically confirmed extra pelvic disease places the case in Stage IVb. In such circumstances there is little point in irradiating the pelvis to consolidate loco-regional treatment. Omental biopsy could avoid unnecessary therapy potentially both surgical (lymphadenectomy) and radiotherapy in those patients. Entry to a clinical trial of a systemic therapeutic agent would be more appropriate management. The manner in which staging should be carried out for early endometrial cancer remains controversial. Recent FIGO guidelines suggest total hysterectomy, bilateral
578
SHORT COMMUNICATION
oophorectomy and peritoneal washings through a vertical incision as the minimum required. Pelvic and para-aortic lymphadenectomy may or may not be performed. The Medical Research Council ASTEC study may answer important questions relating to lymphadenectomy when completed. However, pelvic lymphadenectomy even in expert hands is unlikely to be achieved without some morbidity in less fit women. Recognised risk factors associated with endometrial cancer are obesity, cardiovascular disease, diabetes and age. These complications make up to 70% of women with early stage endometrial cancer less fit for general anaesthesia and major surgery and it may be imprudent to conduct staging according to FIGO guidelines. Omental biopsy is unlikely to increase morbidity over hysterectomy alone and could be performed in situations where pelvic lymphadenectomy would entail increased risk for the patient. We conclude that the application of this surgicopathological staging approach in our series has influenced the management of around 15% of our high risk patients
with no obvious detriment to the low risk women who have also undergone an omental biopsy.
References 1. Woolas RP, Oram DH. Current management of endometrial carcinoma. In: Studd J, editor. London: RCOG Press, 1994:181 – 194. 2. Orr Jr JW, Holloway RW, Orr PF, Holimon JL. Surgical staging of uterine cancer: an analysis of perioperative morbidity. Gynecol Oncol 1991;42:209 – 216. 3. Quinn MA. Pelvic lymphadenectomy in high risk endometrial cancer. Int J Gynecol Cancer 1996;6:102 – 107. 4. Kadar N, Homesley HD, Malfetano JH. Positive peritoneal cytology is an adverse factor in endometrial carcinoma only if there is other evidence of extrauterine disease. Gynecol Oncol 1992;46:145 – 149. 5. Sutton GP. Peritoneal cytology in endometrial carcinoma. Cancer Treat Res 1989;49:41 – 52. 6. Chen SS, Spiegel G. Stage I endometrial carcinoma. Role of omental biopsy and omentectomy. J Reprod Med 1991;36:627 – 629. Accepted 17 December 2001
D RCOG 2002 Br J Obstet Gynaecol 109, pp. 576 – 578