Copyright to Australian Family Physician. Reproduced with permission. Permission to reproduce must be sought from the publisher, The Royal Australian College of General Practitioners.BACKGROUND Epithelial ovarian cancer presents most often as late stage disease due to a lack of effective screening tests and vagueness of symptoms. OBJECTIVE This article outlines the diagnosis and management of ovarian cancer. DISCUSSION Women with suspected ovarian cancer are best managed in a gynaecological treatment unit offering multidisciplinary care. Surgery is usually needed both to make a diagnosis and for definitive treatment and referral to a specialty trained gynaecological oncologist is appropriate. Most women will also require chemotherapy. Ovarian cancers have good sensitivity to several drugs but relapse rates are high. This means that ovarian cancer is now seen as a chronic disease with often several episodes of remission, relapse and treatment. The psychological impact of this diagnosis both on the woman and her family are significant and best dealt with proactively.Margaret Dav

Davy, M.

Adelaide Research &amp; Scholarship

THEME Gynaecological malignancies130  Reprinted from Australian Family Physician Vol. 36, No. 3, March 2007Margaret Davy AM, MBBS, FRANZCOG, FRCOG, CGO, is Director, Gynaecological Oncology, Royal Adelaide Hospital, South Australia, and Visiting Consultant-Gynaecological Oncologist, Royal Darwin Hospital, Northern Territory. margaret.davy@adelaide.edu.auIn 1999, ovarian cancer was the eighth commonest cancer and the sixth most common cause of death from cancer in Australian women (Table 1).1 This in no small way reflects the late presentation for the majority of women.SymptomatologyEpithelial ovarian cancers tend to occur most commonly in the peri- and post-menopausal woman. Symptoms are usually vague – accounting for the late presentation – and may include:• pressure symptoms – bladder, bowel• increased abdominal girth• fatigue• gastrointestinal symptoms – indigestion or lack of appetite, change in bowel habits, constipation, or• less commonly, pain.Vine et al3 reported that 92% of women with invasive ovarian tumours and 84% of borderline cases have symptoms with a median duration of 4 months. Obviously not all peri- or post-menopausal women with these symptoms will have ovarian cancer, but symptoms which persist (eg. for 1 month) should be investigated. The question should always be raised: ‘Could this be ovarian cancer?’ The thought that a woman may have a psychosomatic problem should not overrule clinical suspicion of malignancy in women with persistent symptoms. A high level of suspicion is a useful adjunct in making the diagnosis of ovarian cancer particularly:• in women with a family history of ovarian cancer• women over 45 years of age, or • where symptoms appear to persist in the absence of any alternative explanation.InvestigationClinical examination, including a pelvic examination may reveal:• increased girth either ascites, or• an abdominal mass (omental cake), and/or• pelvic mass – filling the pouch of Douglas (best felt by recto-vaginal examination).Depending on f indings and symptomatology, a transvaginal ultrasound or computerised tomography (CT) scan of the abdomen and pelvis may confirm any physical findings. Gastrointestinal symptoms may frequently lead to a referral for endoscopy – which will be negative. Both the general practitioner and the endoscopist need to consider ovarian cancer in these cases where symptoms persist and are not explained. Tumour markers (CA-125) may be elevated (see the article by Neesham this issue about the role of CA-125 in ovarian cancer screening).Ovarian cancerDiagnosis and managementBACKGROUNDEpithelial ovarian cancer presents most often as late stage disease due to a lack of effective screening tests and vagueness of symptoms.OBJECTIVEThis article outlines the diagnosis and management of ovarian cancer.DISCUSSION Women with suspected ovarian cancer are best managed in a gynaecological treatment unit offering multidisciplinary care. Surgery is usually needed both to make a diagnosis and for definitive treatment and referral to a specialty trained gynaecological oncologist is appropriate. Most women will also require chemotherapy. Ovarian cancers have good sensitivity to several drugs but relapse rates are high. This means that ovarian cancer is now seen as a chronic disease with often several episodes of remission, relapse and treatment. The psychological impact of this diagnosis both on the woman and her family are significant and best dealt with proactively.Reprinted from Australian Family Physician Vol. 36, No. 3, March 2007  131DiagnosisThe definitive diagnosis is made surgically. Where suspicion is high, surgery is best performed by a gynaecological oncologist with training in all aspects in the management of ovarian cancer. At this surgery, staging is also undertaken as well as definitive treatment.4 A total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, examination of pelvic and para-aortic lymph nodes, as well as a careful search throughout the peritoneal cavity to detect and remove any tumour deposits will be undertaken. Occasionally where tumour affects the bowel, bowel resection, usually with primary reanastomosis, may also be necessary. The aim of the surgery therefore, is to remove all tumour deposits as much as possible to leave no or minimal tumour burden remaining. The stage of the tumour is therefore determined at this surgery and gives a guide to prognosis. The stage of the tumour acts as a guide to further management (Table 2).What is ‘standard management’?Ideally each woman should be managed in the setting of a multidisciplinary team, where each member has expertise in ovarian cancer care specifically, as well as their own field. There is evidence that outcomes for women in this setting are maximised.5,6 With exception of certain women whose disease is still stage I, the majority of women will expect to be offered chemotherapy after surgery. The gold standard currently is paclitaxel and carboplatin combination.7 The standard dose of paclitaxel of 175 mg/m2 and carboplatin AUC x 6 given every 3 weeks is generally well tolerated.8 This is given usually in a day centre one day every 21 days for six cycles. Blood tests to ensure bone marrow recovery before each cycle are undertaken. A consultation also occurs before each cycle to investigate the efficacy of the treatment as well as management of any side effects from chemotherapy. Tumours have a good sensitivity to these drugs and about three-quarters may expect a positive response. Chemotherapy usual ly  commences as soon as practical after surgery when bowel function has recovered. There is no advantage in delaying chemotherapy because of wound healing. There is also no evidence to suggest that more than six cycles of chemotherapy offer any further advantage. As well as monitoring bone marrow function the tumour marker CA-125 can be used as an additional means of assessing response. CA-125 has a half life of approximately 6 days. Provided the CA-125 continues to fall, treatment should continue to maximum of six cycles.Follow up after primary treatmentPresent evidence does not support the use of any maintenance or consolidation therapy after initial treatment.9 CA-125 is also used to monitor for tumour relapse. A rise to more than twice the upper limit of normal during follow up accurately predicts tumour relapse.10 Despite the relatively high response to chemotherapy, the majority of advanced ovarian cancer patients will relapse. The interval between the end of first line therapy and relapse (the so-called ‘treatment free interval’) is of prognostic significance. The longer the treatment free interval, the higher the likelihood of a further worthwhile response.11 Experience would suggest that a treatment free interval greater than 12 months is associated with a significant number of patients deriving worthwhile benefit from re-treatment. Women whose disease recurs in less than 6 months (platinum refractory) usually do not respond to other forms of therapy. In all cases of second line therapy, it is important to monitor patients carefully and only continue treatment if there is objective evidence of response. It is essential that the quality of life of the woman is a major part of assessment.Radiation therapyFollowing surgery, chemotherapy has been the major thrust of treatment, however, radiation therapy has been useful in some women. The systematic study of radiation therapy has been hampered by poor accrual to large randomised trials.  Whole Abdominal Radiotherapy (WART) has been used in patients with stage I, II and III disease with no macroscopic disease in the upper abdomen after completion of surgery.12 The amount of radiation delivered to the abdomen is limited by the normal organs in the field. The dose is limited to 45–50 Gy in relatively low fractions of up to two Gy per fraction. Most patients experience acute side effects including nausea, vomiting and diarrhoea. Myelosuppression has been a common reason for treatment interruptions. Up to 10% of patients do not complete therapy. The late complications of WART include chronic diarrhoea, transient liver enzyme disturbance, basal pneumonitis, cystitis and bowel obstruction.Table 1. Ovarian cancer in Australian women in 19991,2•	1173	women	diagnosed	with	ovarian	cancer•	731	women	died	from	ovarian	cancer•	5948	years	of	life	lost	under	the	age	of	75	years•	Relative	survival	nationally	of	42%	at	5	years	after	diagnosis	in	1992–1997•	The	most	common	cause	of	death	from	gynaecological	malignancyOvarian cancer – diagnosis and managementTHEME132  Reprinted from Australian Family Physician Vol. 36, No. 3, March 2007Common side effects of therapySurgeryThe common postsurgical problems of infection, thrombosis and poor wound healing are similar to any other surgery. Postoperative ileus may be higher because of bowel involvement with tumour.ChemotherapyWith the advent of modern antinausea medication, nausea and vomiting are usually a thing of the past when undergoing chemotherapy. Medication will include a 5HT3 antagonist and possibly also an anxiolytic. Both paclitaxel and platinum can produce peripheral neuropathy and women must be warned of this possibility. The neuropathy may often not appear until quite late in the cycle of chemotherapy or even after it is completed. Paclitaxel can also cause muscle and joint pain that may last from a few hours to several days in the first week after therapy. Bone marrow suppression may occur. Carboplatin may be more responsible for platelet depletion whereas both drugs equally will affect neutrophils.PrognosisThe majority of patients will present with stage III or IV disease (about 75%). While the response rates to primary chemotherapy with paclitaxel and carboplatin are relatively high, the majority of women will eventually relapse and succumb to their disease. Survival rates are in the order of 40%.Quality of lifeOvarian cancer should be seen as a chronic disease with often several episodes of remission, relapse and treatment. It is essential that the quality of life of women with ovarian cancer is a major part of assessment and consideration of quality of life issues underpin any treatment decisions. There is Level one evidence that psychosocial intervention can result in lower rates of anxiety and depression, and nausea and vomiting for patients with cancer.13 Psychosocial interventions can include counselling and relaxation therapy, education programs to improve pain control, and cognitive behavioural interventions, all of which have shown positive benefits.Table 2. Staging of ovarian cancerStage I Growth	limited	to	ovaries	onlyStage IA One	ovary,	no	ascites,	no	tumour	on	external	surface,	capsule	intactStage IB Both	ovaries	involved,	no	ascites,	no	tumour	on	external	surface,	capsule	intactStage IC IA	or	IB	with	tumour	on	surface,	capsule	ruptured,	malignant	ascites	or	positive	washingsStage II Pelvic	extension	onlyStage IIA Extension	and/or	metastasis	to	uterus	and/or	fallopian	tubesStage IIB Extension	to	other	pelvic	tissuesStage IIC IIA	or	IIB	with	tumour	on	surface	or	capsule	ruptured,	malignant	ascites	or	positive	washingsStage III Tumour	involving	one	or	both	ovaries	with	peritoneal	implants	outside	the	pelvis	and/or	positive	retroperitoneal	or	inguinal	nodesStage IIIA Tumour	grossly	limited	to	the	true	pelvis	with	negative	nodes	but	histologically	confirmed	microscopic	seeding	of	abdominal	peritoneal	surfacesStage IIIB Tumour	involving	one	or	both	ovaries,	histologically	confirmed	implants	on	abdominal	peritoneal	surfaces	<2	cmStage IIIC Abdominal	implants	>2	cm	and/or	positive	retroperitoneal	or	inguinal	nodesStage IV Growth	involving	one	or	both	ovaries	with	distant	metastasis.	If	pleural	effusion	present,	positive	cytology;	parenchymal	liver	metastasisOvarian cancer – diagnosis and management THEMEReprinted from Australian Family Physician Vol. 36, No. 3, March 2007  133ConclusionIn women with epithelial ovarian cancers symptoms are usually vague and as a consequence presentation and/or diagnosis is often late. A high level of suspicion is important in making the diagnosis of ovarian cancer particularly in the peri- and post-menopausal woman, those with a family history of ovarian cancer, and when symptoms persist for more than 1 month. Women with suspected ovarian cancer are best managed in a gynaecological treatment unit offering multidisciplinary care. Surgery is usually needed both to make a diagnosis and for definitive treatment. Most women will also require chemotherapy. Ovarian cancers have good sensitivity to several drugs but relapse rates are high.Conflict of interest: none declared. References 1. Australian Institute of Health and Welfare (AIHW) and Australasian Association of Cancer Registries (AACR): Cancer in Australia 1999. Cancer Series 20, Canberra: Australian Institute of Health and Welfare, 2002.2. Australian Cancer Network. Clinical practice guidelines for the manage-ment of women with epithelial ovarian cancer. National Breast Cancer Centre, 2004.3. Vine MF, Ness RB, Calingaert B, et al. Types and duration of symptoms prior to diagnosis of invasive or borderline ovarian tumour. Gynecol Oncol 2001;83:466–71.4. Carney ME, Lancaster JM, Ford C, et al. A population based study of patterns of care for ovarian cancer: who is seen by a gynaecologic oncologist and who is not? Gynecol Oncol 2002;84:36–42.5. Junor EJ, Hole DJ, McNulty L, et al. Specialist gynaecologists and survival outcome in ovarian cancer: a Scottish National Study of 1866 patients. Br J Obstet Gynaecol 1999;106:1130–6.6. Junor EJ, Hole DJ, Gilles CR. Management of ovarian cancer: referral to a multidisciplinary team matters. Br J Cancer 1994;70:363–70.7. Aabo K, Adams M, Adnitt P, et al. Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomised trials. Advanced Ovarian Trialists Group. Br J Cancer 1998;78:1479–87.8. du Bois A, Neijt JP, Thigpen JT. First line chemotherapy with carboplatin plus paclitaxel in advanced ovarian cancer: a new standard of care? Ann Oncol 1999;10(Suppl 1):35–41.9. Lambert HE, Rustin GJ, Gregory WM, et al. A randomised trial of five versus eight courses of cisplatin or carboplatin in advanced epithelial ovarian carcinoma. A North Thames Ovary Group Study. Ann Oncol 1997;8:327–33.10. Rustin GJ, Nelstrop AE, Tuxen MK, et al. Defining progression of ovarian carcinoma during follow up according to CA125: a North Thames Ovary Group Study. Ann Oncol 1996;7:361–4.11. Blackledge G, Lawton F, Redman C, et al. Response of patients in phase II studies of chemotherapy in ovarian cancer: implications for patient treatment and the design of phase II trials. Br J Cancer 1989;59:650–3.12. Dembo AJ. Epithelial ovarian cancer: the role of radiotherapy. Int J Radiat Oncol Biol Phys 1992;22:835–45.13. Devine EC, Westlake SK. The effects of psychoeducational care provided to adults with cancer: meta-analysis of 116 studies. Oncol Nurse Forum 1995;22:1369–81.CORRESPONDENCE email: afp@racgp.org.au

Ovarian cancer - diagnosis and management

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Ovarian cancer - diagnosis and management

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Ovarian cancer - diagnosis and management

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