Ovarian cancer remains the most lethal of gynaecological malignancies, as it has been for the last 30 years.
Although the proportion of women surviving beyond five years after diagnosis has increased by 16% (to 46% currently), this improvement is overshadowed by the significantly better five-year survivals from other common female tumours like breast, uterine and cervical cancer.
Survival rates must improve
Whilst acknowledging that the comparison is unfair - ovarian cancer presents at an advanced stage and is not currently the subject of a screening programme - there is no doubt that the lack of greater survival improvement is disappointing.
After all, this has been the era of reorganisation of cancer services across the UK, subspecialisation of gynaecological cancer surgery, sequencing of the genome and the development of targeted therapies.
Ovarian cancer is it is too rare to be in the realm of common knowledge but too common to be ignored. Although it is estimated to affect 1 in 50 women during their lifetime, this statistic pales in comparison to breast cancer, which affects 1 in 8 women. Another issue is that although the age-range of those affected by the disease is wide, from 18 to 90 years in our practice, its incidence peaks in the post-menopausal years.
As was recently described in Lindsay Forbes’ paper in the BJC, the over 50s in the UK are stoics by nature, and a combination of fear, embarrassment and a tendency to keep a 'stiff upper lip' prevents them visiting their doctors as often as they should.
Patients' stiff upper lip
Many of our patients described their reluctance to 'make a fuss' about the persistent abdominal bloating, changing bowel habits or urinary problems that heralded the arrival of their disease.
The chameleon nature of these symptoms means that, for many who do attend their GP, an incorrect diagnosis of diverticulitis or irritable bowel syndrome is sometimes made - abetted by the unreliability of the CA125 tumour marker test that is only elevated in 50% of early stage disease.
The net result is that one third of women with ovarian cancer are diagnosed in A&E. Charities like Ovarian Cancer Action have made huge progress in improving awareness among women and their GPs. But even in an ideal world of 100% awareness there would still be significant mortality from ovarian cancer because of its innate molecular heterogeneity.
Although the expression of many genes is altered in ovarian cancer, a universal 'driving mutation' has yet to be found. Without an Achilles' heel to aim for, molecularly targeted therapies have failed to show strong effect, often causing the cancer to pause rather than significantly regress. This means that treatment for the disease is still centred round surgery and chemotherapy, just as it has been for the last 30 years.
Nevertheless subgroups of ovarian cancer patients can obtain significant survival benefit from targeted therapies, such as those with tumours carrying BRCA mutations which are responsive to poly-ADP ribose polymerase (PARP) inhibitors. Another example is the targeted angiogenesis inhibitor Avastin (bevacizumab) which has recently been shown to improve survival outcomes in patients who are at highest risk of relapsing from ovarian cancer.
Notwithstanding the cost implications, when added to our standard armoury of chemotherapy, these targeted therapies have the potential to incrementally improve survival. Collaborations between translational research centres such as the British Translational Research in Ovarian Cancer Consortium (BriTROC) in the UK and the European Network for Translational Research in Ovarian Cancer (EuTROC) in Europe have recently been established to maintain the impetus of clinical research into ovarian cancer.
The focus of these collaborations is to ensure that clinical trials are designed not just to ask whether a new drug is effective but to ask: 'why is it effective?' and 'How can it be predicted to be effective in others?'. This is achieved by collectively monitoring the molecular changes that occur within tumours as a result of treatment. It is likely that initiatives such as these will spawn a new generation of molecular targets in the coming years with knock-on improvements to survival.
Stoicism is also a factor among ovarian cancer survivors. For those either cured of their cancer or with recurrent but clinically containable disease, life is rarely ever the same. For some, the experience of ovarian cancer is one of life’s 'blips' but for others it marks a sudden deterioration in physical and mental health, income, social status and libido.
I mention the latter because, in an online survey conducted by Ovarian Cancer Action, the majority of participants attributed the disease as having a negative effect on their sex life, with over two-thirds describing severe vaginal dryness as the cause. That so many survivors suffer this easily reversible condition highlights the unwitting collusion of embarrassment that exists between doctors and their stoical patients.
Similarly, depression is common but invariably unreported in ovarian cancer survivors, despite being highly responsive to early intervention. Ovarian cancer has often been described as a silent killer, but the silence does not just describe the disease but often extends to that of the patients and their doctors alike.
March 2013 should be the month when we collectively soften our upper lips in recognition that - if the barriers of stoicism and embarrassment were lifted - fewer women would die of ovarian cancer and a greater number would recover more fully from treatment to lead better and happier lives.
Ovarian Cancer Action is launching a dedicated helpline for GPs and healthcare professionals to access general information about the disease. The helpline number is: 0207 380 1747 and will be accessible Monday – Friday from 9am – 5pm. Click here for more information