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Ovarian cancer is easy to miss, but don’t let that lead to delays in diagnosis
Ovarian cancer is easy to miss, but don’t let that lead to delays in diagnosis
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Here at New Zealand Doctor Rata Aotearoa we are on our summer break! While we're gone, check out Summer Hiatus: Stories we think deserve to be read again! This article was first published on 16 Feburary 2022, and highlights the roles primary care has to play in addressing this serious cancer
- Ovarian cancer is a significant health issue in New Zealand – women have a lower chance of survival at five years than many comparable countries.
- GPs have an essential role to rule out ovarian cancer in symptomatic women and diagnose those with cancer in a timely manner.
- Clear nationally applicable guidelines are required to ensure equitable and prompt access to investigations.
- In addition, greater resources, improved treatment availability and further research are urgently required if this situation is to be addressed.
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While ovarian cancer is an uncommon cancer (350 women a year1 ), in New Zealand, it is the fifth most common cause of female cancer death.2 It is also the leading cause of gynaecological cancer death (including Māori and Pacific),2 killing as many women as all other gynaecological cancers combined.1
Time to diagnosis is a significant modifiable factor that may impact survival. The historical view that ovarian cancer is a “silent cancer” was disproven in 2000.3 Research shows most women with ovarian cancer experience symptoms – many in the earlier stages of the disease.4 This provides an opportunity for earlier diagnosis, which could improve outcomes.5
The symptoms women present with are variable but can include one or more of: bloating/distension, early satiety, urinary frequency/urgency, abdominal/pelvic/back pain and bowel habit changes. Other symptoms are also possible, including indigestion, nausea, fatigue, abnormal vaginal bleeding/discharge, unexplained weight changes and painful intercourse.3,5
While it’s true these symptoms are very common in general practice, in women without ovarian cancer, they are usually mild and occur on five or fewer days a month.6 In contrast, symptoms in ovarian cancer occur more frequently.7
Consideration should be given to symptoms that occur often and are new, unusual or worsening.
Because of the non-specific nature of ovarian cancer symptoms, it is common for these to initially be misattributed to irritable bowel syndrome (most common and associated with significantly delayed diagnosis), other gastrointestinal disorders, ovarian cysts, urinary tract infections, menopause, stress or depression.3,8
On average, a GP with 2000 patients will see one patient with ovarian cancer every four and a half years.8 The Diagnosing Ovarian Cancer Early (DOvE) pilot project found a cancer incidence of one in 58 women aged 50 and over who had been experiencing any symptoms for more than two weeks and less than one year. Just under half were found to have ovarian cancer (1 in 138), with the majority of the remainder receiving a diagnosis of early-stage uterine cancer.5
Ovarian cancer is much more common in the postmenopausal population. However, in New Zealand, it is worth noting that one in eight cases occur in women younger than 45 years, and in the 20–44 age group, ovarian cancer remains the fifth most common cause of female cancer death.2 Younger age is a risk factor for delayed diagnosis.3
Approximately one in 10 ovarian cancers are hereditary.9 Both BRCA1 and BRCA2 mutations, and hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome), can significantly increase the risk of ovarian cancer. Depending on the mutation, the risk can range from 8 to 44 per cent lifetime risk.10,11 These mutations can be inherited from either genetic parent, so it is important to note if there is a family history of cancer – in particular, breast, ovarian or colorectal cancer.
Of less clinical significance, a negative history of oral contraceptive use, nulliparity and endometriosis are associated with an increased risk of ovarian cancer (but the absolute lifetime risk change is small).9
Because most serous ovarian cancers originate from the fallopian tube, opportunistic salpingectomy significantly reduces an individual’s risk of ovarian cancer.12
Practitioners in countries with better survival are more willing to order an ultrasound at first visit for the following scenario: a 53-year-old woman who had her last period six months ago and has experienced abdominal pain for the past three weeks; she has had no other symptoms and the same sexual partner for 20 years.13
Annual screening in low-risk women can sometimes identify ovarian cancer before symptoms develop,14 but it is not recommended as it has not been shown to significantly improve survival.15 There is no consensus around its use in high-risk populations. In contrast, prompt investigation in symptomatic women is likely of benefit.5
Investigation for ovarian cancer usually includes a pelvic exam, cancer antigen 125 (CA-125) blood test and transvaginal ultrasound (TVUS).16 Though pelvic exam has a low sensitivity when used as screening,17 it remains an important part of assessment in symptomatic patients. DHBs report decreased wait times for TVUS when pelvic exam is positive.
A recent study in the UK found CA-125 to be more predictive of ovarian cancer than previously thought – 3.4 per cent of women under age 50 and 15.2 per cent of women over 50 with a CA-125 ≥35U/ml received a diagnosis of ovarian cancer. The same study found 12.3 per cent of women with elevated CA-125 were diagnosed with another cancer.18
However, a normal result does not exclude ovarian cancer. In the same study, 23 per cent of women with ovarian cancer had a normal result.18 A CA-125 <35U/ml is more likely in younger women with ovarian cancer,18 and it is normal in half of all women with early ovarian cancer.19 In pre-menopausal patients, measurements should be avoided immediately before or during menstruation as this can inflate the result.20
It is possible for both TVUS and CA-125 results to be initially normal (particularly in low-volume, high-grade serous5 ), which is why patients should be encouraged to return if symptoms persist. Detection rates may be improved when TVUS is normal by repeating CA-125 measurements four to six weeks later if >25U/ml, or four months later if <25U/ml.5
The ovarian cancer situation in New Zealand is concerning. Compared with Australia, 16 per cent less women survive five years in New Zealand.21
The International Cancer Benchmarking Partnership (ICBP) is an international collaboration, initiated by the UK, investigating survival differences among seven high-income countries with comparable health systems, including New Zealand.21
Recent research shows New Zealand’s five-year ovarian cancer survival rate of 36 per cent has improved the least of all participating countries in the past 15 years,21 while a Christchurch study found advanced ovarian cancer survival rates did not change at all over a 10-year period.22 UK’s survival has now overtaken that of New Zealand, although, along with Ireland, they also significantly lag behind other participating countries.21
Countries that have shown a marked improvement in ovarian cancer survival have put significant investment into awareness, early diagnosis and sub-specialisation of cancer services, and improved access to a number of anticancer drugs and clinical trials.
Cure Our Ovarian Cancer (COOC) has conducted two surveys of the New Zealand Ovarian Cancer Support Group, investigating factors (2020, 60+ respondents) and perceptions (2021, 40+ respondents) relating to diagnosis. The results suggest symptomatic women in New Zealand may wait significantly longer to see a doctor than women in Australia, and longer to receive a diagnosis once they do.
Most COOC survey respondents delayed presentation to their doctor, with just 8 per cent presenting in the first month compared with 55 per cent reported in Australia.23 Over half reported feeling at times like a hypochondriac before their diagnosis.
When they presented to a doctor, over half of women reported that they felt their doctor did not take their symptoms seriously. On average, women had to visit their doctor three to five times before receiving the necessary testing to diagnose them.
An audit by New Zealand gynaecological oncologist Patrick Keating found 34 per cent of women were diagnosed via the emergency department in 2019. Of note, one in five COOC survey respondents reported seeing a doctor for over a year before being diagnosed. This suggests overseas research indicating ovarian cancer is unlikely when symptoms are present for more than a year7 may not apply to the New Zealand situation.
Difficulties accessing consistent evidence-based information is an issue. Clearly, national guidelines on the assessment of symptoms that could be ovarian cancer are required to improve the diagnostic pathway for prompt diagnosis. These should include the use of pelvic examination, CA-125 and TVUS.
Respondents to a COOC survey distributed through the RNZCGP newsletter overwhelmingly identified ultrasound access as a significant barrier to earlier diagnosis. Through Official Information Act requests, COOC has found few DHBs include any reference to typical ovarian cancer presentations in their written criteria for assessing ultrasound eligibility, though most subscribe to Health Pathways.
Most DHBs try to see postmenopausal women with CA-125 ≥35U/ml and pre-menopausal women with CA-125 ≥200U/ml within two weeks (MidCentral DHB is an outlier). However, there is significant discordance regarding symptomatic women with lower CA-125 results, with significant wait times in many regions, if indeed they are seen at all.
For pre-menopausal women with CA-125 <200U/ml, and postmenopausal women with CA-125 <35U/ml, private referral is the only option in some regions if the pelvic exam is normal.
During the OIA process, one-fifth of DHBs noted unprompted that referrals rarely included CA-125 test results, so COOC initiated OIA requests for volume of CA-125 tests per DHB. Results are still pending, but the first six responses show significant differences in regional testing rates from 0.7–9.6 per 1000 population.
For comparison, an English report in 2016 found a difference of 0.1–9.0 per 1000 by National Health Service Primary Care Trust.24
According to an ICBP study, primary care doctors in the UK have a significantly lower readiness to investigate on first visit than other countries (New Zealand was not included in the analysis), and this correlates with lower survival.13 COOC’s survey indicated that just one in five women with ovarian cancer received diagnostic investigations on their first visit.
Additionally, a lack of clinical trials and research may also have an impact on local survival. New Zealand women have significantly less access to clinical trials than those in Australia, and disproportionately little research is performed here.
A Te Aho o Te Kahu Cancer Control Agency report stated that ovarian cancer received the least funding of 13 cancers funded by the Health Research Council between 2006 and 2019.25 Since then, just one “ovarian cancer” project has been funded. It focuses entirely on BRCA mutations in women with breast cancer.26
Ovarian cancer incidence and mortality rates are higher in Pacific and Māori women
Where barriers exist to prompt and effective assessment and treatment, they tend to have inequitable impacts. In New Zealand, the following inequities have been documented:
Ethnicity – corrected for age and stage, ovarian cancer incidence and mortality rates are higher in Pacific and Māori women.27
Socioeconomic – women from deprived areas, and Māori and Pacific women, are more likely to not have tumour grade recorded.27 Research from France suggests women of low socioeconomic status have reduced survival because they are less likely to have surgical resection.28
Gender inequity – may also be an issue for ovarian cancer. ACC recently raised the likelihood of gender bias in the New Zealand health system as a contributing factor to why females make fewer ACC claims and have more denials.29 In the UK, almost one in 10 women with ovarian cancer are incorrectly told prior to diagnosis that their symptoms could be due to a mental health condition.30 In the US, relative to lethality, prostate cancer receives over 18 times more research funding than ovarian cancer.31
Jane Ludemann is the founder and chair of Cure Our Ovarian Cancer; Associate Professor Peter Sykes is a Christchurch gynaecological oncologist and chair of the Australian Society of Gynaecologic Oncologists
COOC has a list of useful resources, including a CME module, literature review, symptoms poster and top 10 tips for GPs: cureourovariancancer.org/nz/health-professionals
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- Ministry of Health. Cancer: Historical Summary 1948–2017. September 2020.
- Ministry of Health. Cancer: New registrations and deaths 2013. 2016.
- Goff BA, Mandel L, Muntz HG, et al. Ovarian carcinoma diagnosis. Cancer 2000;89(10):2068–75.
- Hamilton W, Peters TJ, et al. Risk of ovarian cancer in women with symptoms in primary care: population based case-control study. BMJ 2009;339:b2998.
- Gilbert L, Basso O, Sampaslis J, et al. Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol 2012;13(3):285–91.
- Pitts MK, Heywood W, et al. High prevalence of symptoms associated with ovarian cancer among Australian women. Aust N Z J Obstet Gynaecol 2011;51(1):71–78.
- Andersen MR, Goff BA, Lowe KA, et al. Combining a symptoms index with CA 125 to improve detection of ovarian cancer. Cancer 2008;113(3):484–89.
- BMJ Learning. Recognising early symptoms of ovarian cancer. August 2021. https://new-learning.bmj.com/course/10014285
- Sueblinvong T, Carney M. Current understanding of risk factors for ovarian cancer. Curr Treat Options in Oncol 2009;10(1–2):67–81.
- Nakamura K, Banno K, et al. Features of ovarian cancer in Lynch syndrome. Mol Clin Oncol 2014;2(6):909–16.
- Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 2017;317(23):2402–16.
- Naumann RW, Hughes BN, Brown J, et al. The impact of opportunistic salpingectomy on ovarian cancer mortality and healthcare costs: a call for universal insurance coverage. Am J Obstet Gynecol 2021;225(4):397.e1–397.e6.
- Rose PW, Rubin G, Perera-Salazar R, et al. Explaining variation in cancer survival between 11 jurisdictions in the International Cancer Benchmarking Partnership: a primary care vignette survey. BMJ Open 2015;5:e007212.
- Dilley J, Allen P, et al. Symptoms reported by women with screen detected invasive epithelial ovarian cancer in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). 2015. (unpublished)
- Menon U, Gentry-Maharaj A. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 2021;397:2182–93.
- Funston G, Van Melle M, Baun ML, et al. Variation in the initial assessment and investigation for ovarian cancer in symptomatic women: a systematic review of international guidelines. BMC Cancer 2019;19(1):1028.
- Doroudi M, Kramer B, et al. The bimanual ovarian palpation examination in the Prostate, Lung, Colorectal and Ovarian cancer screening trial: Performance and complications. Med Screen 2017;24(4):220–22.
- Funston G, Hamilton W, et al. The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study. PLoS Med 2020;17(10):e1003295.
- Buys SS, Partridge E, Greene MH, et al. Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial. Am J Obstet Gynecol 2005;193(5):1630–39.
- Lehtovirta P, Apter D, Stenman UH. Serum CA 125 levels during the menstrual cycle. Br J Obstet Gynaecol 1990;97(10):930–33.
- Arnold M, Rutherford MJ. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol 2019;20(11):1493–505.
- Yeoh S, Simcock B, et al. Trends in the overall survival rates in women with advanced ovarian cancer in a single tertiary centre in New Zealand. Aust N Z J Obstet Gynaecol 2019;59:861–66.
- Nagle CM, Francis JE, et al. Reducing time to diagnosis does not improve outcomes for women with symptomatic ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 2011;29(16):2253–58.
- Target Ovarian Cancer. Regional Variation in the diagnosis of ovarian cancer in England. 2017. https://targetovariancancer.org.uk
- Te Aho o Te Kahu Cancer Control Agency. He Pūrongo Mate Pukupuku o Aotearoa 2020 – The State of Cancer in New Zealand. https://teaho.govt.nz/reports/cancer-state
- Health Research Council. https://www.hrc.govt.nz
- Firestone RT, Wong KC, Ellison-Loschmann L, et al. Characteristics of ovarian cancer in women residing in Aotearoa, New Zealand: 1993-2004. J Epidemiol Community Health 2009;63(10):814–19.
- Gardy J, Dejardin O, Thobie A, et al. Impact of socioeconomic status on survival in patients with ovarian cancer. Int J Gynecol Cancer 2019;29(4):792–801.
- ACC. ACC’s Delivery to Priority Populations: Women, Part 1. 22 April 2021.
- Target Ovarian Cancer. Pathfinder 2016: Transforming futures for women with ovarian cancer. https://targetovariancancer.org.uk
- Spencer RJ, Rice LW, Ye C, et al. Disparities in the allocation of research funding to gynecologic cancers by Funding to Lethality scores. Gynecol Oncol 2019;152(1):106–11.