Cancer Research UK : Uterine (Womb) Cancer symptoms and treatment

Uterine (Womb) Cancer symptoms and treatment

This section contains information on symptoms, staging and treatment, risk of recurrence/prognosis and screening.

Symptoms of uterine cancer

Around three quarters of women developing endometrial cancer are postmenopausal and 90% of these present with bleeding1. As it is an obvious symptom many women seek advice after only one or two episodes and would be referred for investigation under the rapid referral rules for suspected cancer2. Consequently approximately 75% of all patients with endometrial cancer present with early stage disease confined to the body of the uterus. Other symptoms can include low pelvic pain, vaginal discharge or, in advanced cases, urinary or rectal symptoms.

Distant metastatic disease is an unusual at diagnosis although local metastasis to the lower vagina can lead to a patient presenting with vulvo-vaginal soreness or bleeding. Women with suspected endometrial cancer undergo investigation in a Gynaecological Cancer Unit where clinical examination, ultrasound and hysteroscopy/biopsy can be carried out.

Staging and treatment of uterine cancer

Surgery is the mainstay of both tumour staging and treatment. A woman diagnosed with endometrial cancer usually undergoes total abdominal hysterectomy (TAH) and bilateral salpingo oophorectomy (BSO), although less invasive laparoscopic techniques for both staging and treatment continue to be developed3. Imaging of the tumour is carried out using MRI or CT scan to demonstrate the depth of myometrial invasion, extra-uterine spread and nodal involvement.

The NHS advice is that, patients should be operated on by a cancer specialist in either a Cancer Unit or Cancer Centre4. The ASTEC trial is comparing survival in stage 1 patients treated with conventional surgery and lymphadenectomy or with conventional surgery alone, with the aim of providing clearer evidence on the benefits of this procedure5, findings are expected in the first half of 2006.

The tumour is graded and staged on the hysterectomy specimen according to FIGO (International Federation of Gynaecology and Obstetrics) rules6. Grade will be stated as well, moderately or poorly differentiated (G1, 2, 3). Histological type should be specified and will usually be endometrioid adenocarcinoma. There is no major difference in prognosis between pure endometrioid adenocarcinoma and adenosquamous carcinoma, but the rarer types of serous papillary and clear cell adenocarcinomas have a markedly worse prognosis, with a propensity to distant spread. These should always be classed as G3. Stage and substage is assessed histologically, according to FIGO rules7, with tumours confined to the body of the uterus being classed as stage I, those involving the cervix as stage II, those with spread outside the uterus as stage III and those with bowel, bladder or distant organ involvement as stage IV (Table 6.1).

Table 6.1: International Federation of Gynaecology and Obstetrics (FIGO) staging for carcinoma of the endometrium

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Adjuvant treatment of uterine cancer

For patients with G1 and G2, stage 1a and 1b tumours, prognosis will be excellent and no further treatment should be needed beyond surgery8. For patients with G3 tumours or stage 1c or higher, who have been rendered macroscopically free of disease by surgery, there may be an advantage to adjuvant radiotherapy both for the control of occult nodal disease9 and vaginal vault recurrence10. Many centres will offer these patients adjuvant external radiotherapy to the pelvis, with or without brachytherapy to the vaginal vault. External radiotherapy will give rise to considerably more toxicity than vault brachytherapy11 and that has to be considered in this relatively elderly group of patients, often with co-morbidities, who may only be at low risk of recurrence12, 13

Radiotherapy has consistently been shown to result in a decrease in local recurrence rates but not a significant increase in overall survival10, 14, 15. This appears to be due to the fact that the small minority of patients who relapse often do so at distant sites with or without local recurrence16.

Trials are underway to try to elucidate the roles of external and internal radiotherapy in the adjuvant treatment of high-risk patients and to determine the high-risk prognostic indicators17. The PORTEC2 trial is currently underway and aims to determine the role of external radiotherapy versus brachytherapy. The ASTEC trial5, 18 has been designed to assess the therapeutic role of external radiotherapy in high-risk patients and should report some early radiotherapy results in 2007. The role of platinum-based chemotherapy is currently being studied in G3 tumours and in the serous papillary and clear-cell variants as these behave similarly to their ovarian counterparts in which platinum-based chemotherapy is standard19, 20. One trial has already reported results showing women treated with radiotherapy and chemotherapy for high-risk early-stage tumours had almost half the risk of death of women receiving radiotherapy only over the study period36. There is no role for progestagens as an adjuvant in first-line treatment21.

Treatment for residual, inoperable or metastatic uterine cancer

Fortunately, most patients are rendered macroscopically disease-free by surgery. However, there will be a small number who are unfit for surgery, who have residual disease at the completion of surgery or who develop metastatic disease. For these patients, chemotherapy, radiotherapy and hormonal treatment with progestagens, alone or in combination, need to be considered. Radical brachytherapy to the uterine body can be used in obese patients unfit for either surgery or external radiotherapy, but there is a risk of intrauterine recurrence22.

Risk of uterine cancer recurrence/prognosis

Risk of recurrence is higher in poorly differentiated tumours that have invaded into the myometrium. The PORTEC trial has shown that, in addition to tumour type, grade, stage and substage, the patient’s age is also a factor, with a higher risk of recurrence in older women23,24. It also appears that lymphovascular invasion is a prognostic factor in some early-stage patients25. Lymph node status is closely associated with tumour stage and grade, with approximately 10% of stage 1 and 20% of stage 2 patients presenting with positive pelvic or para-aortic lymph nodes9, 26, 27, compared to almost one quarter of patients with more than two-thirds invasion into the myometrial wall, and about 15% of patients with grade 3 tumours. Other prognostic factors are uterine size, menopausal status and the presence of progestagen receptors 9,28,29.

Uterine cancer screening

At present, there are not screening methods able to detect uterine hyperplasia or cancer with acceptable sensitivity and specificity to make population screening for endometrial cancer a possibility. Cytological sampling is technically viable, but there is currently no evidence from randomised trials to support its use30. Screening studies suggest that ultrasound imaging of the endometrial wall can be reliably used to rule out the presence of endometrial cancer in postmenopausal women experiencing bleeding, but the test carries a high false positive rate in asymptomatic women31, 32. The Cancer Genetics Studies Consortium recommends gynaecological screening for women with HNPCC syndrome, but there is no clear evidence that ultrasound screening of the womb in this group is of benefit33, 34, 35.

References for uterine (womb) cancer symptoms and treatment

Glassburn, J., L. Brady, and P. Grigsby, Endometrium, in Principles and Practice in Radiation Oncology, Perez and Brady, Editor. 1997, Lippincoltt-Raven. p. 1835-52.
National Institiute for Clinical Excellence, Referral guidelines for suspected cancer: Quick reference guide; Clinical Guideline 27; developed by the national collaborating centre for primary care. June 2005.
Homesley, H.D., G. Boike, and G.W. Spiegel, Feasibility of laparoscopic management of presumed stage I endometrial carcinoma and assessment of accuracy of myoinvasion estimates by frozen section: a gynecologic oncology group study. Int J Gynecol Cancer, 2004. 14(2): p. 341-7.
NHS Executive, Manual of Cancer Services Standards. 2001.
Medical Research Council,A Study in the Treatment of Endometrial Cancer, Version 3. 2003
FIGO (International Federation of Gynecology and Obstetrics), Annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet, 1989. 28: p. 189.
Shepherd, J.H., Revised FIGO staging for gynaecological cancer. Br J Obstet Gynaecol, 1989. 96(8): p. 889-92.
Curtin, J.P. and F. Shapiro, Adjuvant therapy in gynecologic malignancies. Ovarian, cervical, and endometrial cancer. Surg Oncol Clin N Am, 1997. 6(4): p. 813-30.
Creasman, W.T., et al., Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer, 1987. 60(8 Suppl): p. 2035-41.
Aalders, J., et al., Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol, 1980. 56(4): p. 419-27.
Potish, R.A. and K.E. Dusenbery, Enteric morbidity of postoperative pelvic external beam and brachytherapy for uterine cancer. Int J Radiat Oncol Biol Phys, 1990. 18(5): p. 1005-10.
Ackerman, I., et al., Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy reserved for relapse. Gynecol Oncol, 1996. 60(2): p. 177-83.
Greven, K.M., et al., Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation. Int J Radiat Oncol Biol Phys, 1991. 21(4): p. 919-23.
Kucera, H., N. Vavra, and K. Weghaupt, Benefit of external irradiation in pathologic stage I endometrial carcinoma: a prospective clinical trial of 605 patients who received postoperative vaginal irradiation and additional pelvic irradiation in the presence of unfavorable prognostic factors. Gynecol Oncol, 1990. 38(1): p. 99-104.
Irwin, C., et al., The role of adjuvant radiotherapy in carcinoma of the endometrium-results in 550 patients with pathologic stage I disease. Gynecol Oncol, 1998. 70(2): p. 247-54.
Podczaski, E., et al., Detection and patterns of treatment failure in 300 consecutive cases of "early" endometrial cancer after primary surgery. Gynecol Oncol, 1992. 47(3): p. 323-7.
Keys, H.M., et al., A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol, 2004. 92(3): p. 744-51.
Blake, P.R., Post-operative adjuvant radiotherapy for carcinoma of the endometrium. Clin Oncol (R Coll Radiol), 2003. 15(5): p. 248-9.
Greven, K., et al., Preliminary analysis of RTOG 9708: Adjuvant postoperative radiotherapy combined with cisplatin/paclitaxel chemotherapy after surgery for patients with high-risk endometrial cancer. Int J Radiat Oncol Biol Phys, 2004. 59(1): p. 168-73.
Morrow, C.P., et al., Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: a Gynecologic Oncology Group Study. Gynecol Oncol, 1990. 36(2): p. 166-71.
von Minckwitz, G., et al., Adjuvant endocrine treatment with medroxyprogesterone acetate or tamoxifen in stage I and II endometrial cancer--a multicentre, open, controlled, prospectively randomised trial. Eur J Cancer, 2002. 38(17): p. 2265-71.
Fishman, D.A., et al., Radiation therapy as exclusive treatment for medically inoperable patients with stage I and II endometrioid carcinoma with endometrium. Gynecol Oncol, 1996. 61(2): p. 189-96.
Creutzberg, C.L., et al.,Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial. J Clin Oncol, 2004. 22(7): p. 1234-41.
Creutzberg, C.L., et al., Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet, 2000. 355(9213): p. 1404-11.
Briet, J.M., et al., Lymphvascular space involvement: an independent prognostic factor in endometrial cancer. Gynecol Oncol, 2005. 96(3): p. 799-804.
Calais, G., et al., Lymphadenectomy in the management of endometrial carcinoma stage I and II. Retrospective study of 155 cases. Clin Oncol (R Coll Radiol), 1990. 2(6): p. 318-23.
Burke, T.W., et al., Intraabdominal lymphatic mapping to direct selective pelvic and paraaortic lymphadenectomy in women with high-risk endometrial cancer: results of a pilot study. Gynecol Oncol, 1996. 62(2): p. 169-73.
Meerwaldt, J.H., et al., Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors. Int J Radiat Oncol Biol Phys, 1990. 18(2): p. 299-304.
Shinohara, S., et al., Histopathological prognostic factors in patients with cervical cancer treated with radical hysterectomy and postoperative radiotherapy. Int J Clin Oncol, 2004. 9(6): p. 503-9.
Robertson, G., Screening for endometrial cancer. Med J Aust, 2003. 178(12): p. 657-9.
Gupta, J.K., et al.,Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis. Acta Obstet Gynecol Scand, 2002. 81(9): p. 799-816.
Langer, R.D., et al., Transvaginal ultrasonography compared with endometrial biopsy for the detection of endometrial disease. Postmenopausal Estrogen/Progestin Interventions Trial. N Engl J Med, 1997. 337(25): p. 1792-8.
Rijcken, F.E., et al.,Gynecologic screening in hereditary nonpolyposis colorectal cancer. Gynecol Oncol, 2003. 91(1): p. 74-80.
Dove-Edwin, I., et al.,The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer, 2002. 94(6): p. 1708-12.
Brown, G.J., et al.,Cancer risk in young women at risk of hereditary nonpolyposis colorectal cancer: implications for gynecologic surveillance. Gynecol Oncol, 2001. 80(3): p. 346-9.
Hogberg, T., et al.,A randomized phase-III study on adjuvant treatment with radiation (RT) {+/-} chemotherapy (CT) in early-stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991). J Clin Oncol (Meeting Abstracts), 2007. 25(18_suppl): p. 5503-.

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