Ovarian cancer

In this episode of PodMD, experienced sub-specialist Gynaecological Oncologist Dr Rhett Morton will be discussing the topic of ovarian cancer, including how a patient would typically present, the treatment options available, the warning signs to look out for, the likelihood of recurrence, when to refer and more.


RACGP

  • Transcript
    Please note this is a machine generated transcription and may contain some errors.
    *As always, all in this PODMD podcast is intended for health professionals and the comments are of a general nature. Information given is not intended as specific medical advice pertaining to any given patient. If you have a clinical issue with one of your patients please seek appropriate advice from a colleague with expertise in the area.

    Today I’d like to welcome to the PodMD studio Dr Rhett Morton

    Dr Rhett Morton is an experienced sub-specialist Gynaecological Oncologist who treats and manages patients with confirmed or suspected gynaecological cancers, pre-cancers and benign gynaecological conditions requiring complex surgery. Dr Morton is based in The Wesley Hospital in Auchenflower.

    Today, we’ll be discussing the topic of ovarian cancer.

    *We do hope you enjoy this podcast but please remember that the advice here is of a general nature and is not intended as specific advice about a given patient. The views and opinions expressed in this podcast are those of the doctor, not PodMD.
    If you do have a patient on whom you require specific advice, then please seek advice from a colleague with appropriate expertise in that area.

    Rhett, thanks for talking with us on PodMD today.

    Rhett : Thank you for having me

    Question 1
    The topic of today’s discussion is ovarian cancer.
    Rhett, can you describe for our listeners about ovarian cancer?

    Rhett: Absolutely. Ovarian cancer is a very broad range of conditions and. And typically when we talk about ovarian cancer, particularly in the medical community and also in the media, we’re most often referring to epithelial ovarian cancer. And the most common type of that is is a subtype called high grade serous carcinoma. And this type of cancer accounts for 75% of all cases of ovarian cancer. There are some rarer types of cancer that affect predominantly younger women being non epithelial cancers and I won’t go into them today, but that they’re quite a broad topic in themselves and being rare cancers are also unfortunately quite under researched in comparison to the more common high grade serous carcinoma . So ovarian cancer going forth into the podcast when I refer to ovarian cancer, I’m going to be talking about epithelial ovarian cancer and that term really encompasses fallopian tube cancer, ovarian cancer and also a related condition called primary peritoneal cancer and we lump them all together. All of the research that we have on this condition have been done lumping these three conditions together. And the predominant subtype in all of the research essentially is this high-grade serous carcinoma.

    And so this ovarian cancer is the second most common gynecological cancer in developed countries and in Australia about 1800 new cases are diagnosed every year and unfortunately about 1000 women die from this cancer in Australia each year. As I said, it’s unfortunately the deadliest gynecological cancer and currently the five year overall survival with his diagnosis is only 50%. And unfortunately little gains have been made in this over the last 40 years. But excitingly, actually over the last five years, there’s been some new developments and there are some new treatments on the horizon and also in use. And it is, I believe the most researched area currently within gynecological oncology.

    Question 2
    How would a patient with ovarian cancer typically present?

    Rhett: So unfortunately, most women with ovarian cancer will present with advanced stage disease, so stage 3 and 4 disease. And the reasons for that, we believe that the presenting symptoms are often incredibly vague and they’re non specific and this results in women presenting late with these symptoms. The most common symptoms that people report, and it’s usually only in retrospect after their diagnosis, is that they may have experienced bloating, early satiety, they may have other significant bowel change, such as constipation, or just general change in their usual bowel habit.

    They may experience abdominal or pelvic discomfort or pain. They may have noticed some increasing abdominal girth, perhaps that their clothing is being becoming a bit tighter. They may have experienced some weight gain or even weight loss. Occasionally they can have abnormal vaginal bleeding or discharge. We do also see women who are diagnosed with ovarian cancer that have other symptoms, such as their main presenting symptom, may be some dyspnea or shortness of breath, or they may describe some chest pain, and typically that is a sign of development of a pleural effusion. Women may present in quite an acute state with an acute bowel obstruction. And they may also present with symptoms of a paraneoplastic syndrome such as hemolytic anemia, nephrotic syndrome, or hypercalcemia.

    Question 3
    What are the risks of the condition?

    Rhett: The overall lifetime risk for a woman in Australia is around 1.5 to 2%. And the main risk for development of this condition is really age. It’s more common in women after the menopause, but we do see a reasonable amount of women with ovarian cancer diagnosed between the ages of 30 and 50. Traditionally, the risk factors that have been recognised are related to essentially lots of ovulation over the lifetime of a woman and the factors that play into that would be nulliparous or not having any children, having had their first menstrual period at an early age. And their last menstrual period at a late age and through some of the research around that, we now know that the oral contraceptive pill is protective or offers some risk reduction against ovarian cancer. And we think that’s probably due to suppression of ovulation. And then interestingly, over the last couple of years have come to realize that what we always thought was ovarian cancer in terms of high grade serous carcinoma, we know now that that subtype of ovarian cancer actually almost always starts in the fallopian tube. And there are there are well recognized pre cancerous changes that can be seen in the fallopian tube and a lot of women who are diagnosed with ovarian cancer.

    And so the pathogenesis is thought to be that these precancerous changes can form an early cancer in the fallopian tube. And then those cancerous cells essentially float down, implant on the ovary and start to grow, and similarly those cells are also able to float through the peritoneal fluid inside the peritoneal cavity implant on peritoneal surfaces and start to grow, and that’s the main mode of spread of this cancer. The main hereditary risk factor is the BRCA gene mutation, and there is a panel of other mutations that that are also place women at higher risks, but the BRCA mutation either type 1or type 2 are the main risks that that we see women in regards to. For women with the BRCA 1 gene mutation, the increased risk for her developing ovarian cancer over her lifetime goes up to 45%. And for women with the BRCA 2 mutation, this is around lifetime risk of 20%.

    Question 4
    What are the treatment options?

    Rhett: So the treatment options for women with ovarian cancer depends on what stage of disease they present with. For women who present with presumed early-stage disease, meaning that they have perhaps an ovarian mass and no signs of any spread of that outside of the pelvis on imaging. The mainstay of treatment is surgery up front, and we typically perform that surgery through a vertical midline laparotomy. For me and standard surgical management would be a total hysterectomy, removing their uterus and cervix, fallopian tubes and ovaries, and then we go on to do staging procedures. So taking some peritoneal washings, peritoneal biopsies, doing an omentectomy, and in some cases pelvic and periodic lymph node dissection.

    Standard treatment after that is to follow with six cycles of adjuvant chemotherapy and the agents used are called carboplatin and paclitaxel and there’s been lots of studies on different agents and different numbers of cycles, but essentially the standard of care currently based on that research is 6 cycles of carboplatin and paclitaxel. For women who present with advanced age disease, so that’s radiological evidence of spread outside of the pelvic cavity to the abdominal cavity or to the chest cavity. The options for treatment really comprise a combination of both surgery and chemotherapy, and we use them in a different order depending on patient factors and also patient preferences. So the options would be having surgery up front, which we term as cytoreductive or debulking surgery to remove all of the visible tumour within the abdominal pelvic cavity, including the pelvic organs, followed by the six cycles of adjuvant chemotherapy. Or we can give neoadjuvant chemotherapy up front, typically three to four cycles in the aim to shrink down the tumour burden and get the patient in a better medical condition. And then proceed with surgery at that point with the same aims, being removing all macroscopic tumour and then they would go on to complete a further 3 cycles of chemotherapy to get to their total of 6. And then nowadays, more so, women are going on some some form of maintenance therapy after they’ve completed their chemotherapy and the main maintenance therapy is bevacizumab or Avastin or PARP inhibitors which we’ll talk a bit more about shortly. But that that’s been one of the major game changes in treatment of this condition over the last five years.

    Question 5
    Have there been any developments in treatment in the last years or are there any in trials or development now?

    Rhett: Yeah. So the main development been probably the most exciting development in all of gynecological cancer in the last 40 years is essentially development of these drugs called PARP inhibitors. And we now know that a lot of the pathogenesis in development of ovarian cancer comes from a deficiency in the DNA repair pathway within cells, and these cancerous cells have deficient DNA repair pathway processes and the main process is called homologous recombination repair pathway and so about 50% of women with ovarian cancer will have either an inherited germline or a intrinsic tumor deficiency in this DNA repair pathway. And the BRCA or the BRACA gene, essentially is an integral part of that pathway. And we know that around 15% of women with ovarian cancer will have an inherited BRCA mutation and then a further 10% will actually have a mutation that has arisen spontaneously in the tumour itself.

    So essentially that that that gives a target where we can use these PARP inhibitors to essentially block out the alternative form of DNA repair that that would usually be used by the body and that really destabilises these cancer cells and results in their death and the research that’s come to light over the last five years shows dramatic improvements in outcome for women. Of the range in the first line setting, so after they’ve had their surgery and their chemotherapy, if they are found to have either a BRCA mutation in their blood or in the tumour, or if their tumour displays other deficiencies in this homologous recombination pathway, women who go on maintenance PARP inhibitors have between a 50 to 70% reduced risk of recurrence and death when they’re on that treatment as maintenance treatment over the first two years. And that’s incredible for being in a place where we’ve not seen any improved outcomes for the last 40 years to now having a drug that we can offer women that reduces their risk of recurrence and death by up to 70%, and it’s actually, you know, if you think that half of all women with ovarian cancer will have a homologous recombination deficiency, we’re talking about 50% of our population of women with cancer who will benefit from this.

    And there’s also similar benefits that have been seen in the in the second and third line, recurrent settings as well. Excitingly, Australia and the PBS started funding this drug from November 2020, and so it’s now available to women in Australia that there are still issues with equity. For instance, it’s not available in New Zealand under a funded scheme. So Australia is quite lucky that it has been funded and is available.

    Question 6
    Are there any warning signs a GP or their patient can look out for?

    Rhett: One of the difficulties with the diagnosis of ovarian cancer is that it may cause very few and subtle symptoms leading up to when patients notice or present to their healthcare professionals. Often these symptoms are gastrointestinal in nature and maybe a change in bowel habit, either diarrhea or constipation. They may feel a bloating sensation or a change in their appetite with early satiety. They may have noticed some abdominal discomfort or pelvic discomfort. Or some abnormal vaginal bleeding or discharge.

    To patients, I really say try and become familiar with what is normal for you and how your body normally feels. If you notice new symptoms or new sensations that are persistent for a period of say, two weeks or longer, even if they feel mild or minor, I would encourage them to present to their GP for assessment. To GP’s I would say have a very high index of suspicion for any woman, particularly post menopause or woman who presents with abdominal pelvic symptoms, even if these at face value appear to be gastrointestinal in nature. And I would encourage them to have a very low threshold to image. Pelvic ultrasound is fairly inexpensive and low morbidity to the patient and that would be the first investigation of choice, plus or minus the CT scan.

    Question 7
    What is the likelihood of recurrence of the condition?

    Rhett: Women diagnosed with advanced ovarian cancer have a very high likelihood of recurrence, unfortunately. Around 3 in 4 women will recur at some point over the first three years after their primary treatment. Maintenance treatments are helping reduce those rates but we haven’t seen a large shift and we do follow women intensively for the first three years with history examination and tumour marker tests to try and detect recurrence early and initiate second line treatment.

    Question 8
    When should a GP refer?

    Rhett: So I think GP should refer to a specialist in the event of an abnormal examination. Or if there is any abnormality on ultrasound or CT imaging or tumour markers. The tumour markers that are useful for evaluation of epithelial ovarian cancer are primarily CA-125. CEA and CIA 19.9. In a pre-menopausal woman HE4 and ROMA score can also be useful. But also I think if you have a patient in front of you that has persistent unexplained symptoms and normal investigations, definitely even a phone call to a specialist or a specialist unit would be recommended to discuss further investigations and potential referral for further assessment.

    Question 9
    What role does the GP play in the treatment of this condition?

    Rhett: I think the GP has a incredibly important role to play, particularly in early detection. Unfortunately, we don’t have a screening system for ovarian cancer and there have been a few very large randomized controlled trials looking at screening systems both in low and high risk populations of women, there was a very large trial that was published within the last three years involving about half a million women in the UK and unfortunately, regular ultrasound and CA-125 levels did not result in women being diagnosed at a precancerous or early cancerous stage that translated into a reduction in mortality. And so I think just having an open mind and a low threshold for further assessment for women who present with symptoms abdominal pelvic symptoms or chest symptoms that are unusual, unexplained and are low threshold to image them.

    A lot of the treatments that we use, as you can imagine, very extensive surgery, long term chemotherapy and maintenance treatments can have a lot of negative effects on women’s quality of life afterwards and survivorship and the GP’s role in in helping with that I think is incredibly important as well. A lot of women suffer issues with sexual dysfunction. They may be rendered menopausal prematurely and struggle with issues around management of that. They may have ongoing toxicity from their treatment, including peripheral neuropathy, fatigue, gastrointestinal toxicity. They may have had complications from surgery, they may be managing a stoma bag, so there are lots of ongoing effects from treatment, and I think one of the really important roles that GPS. And players supporting the patient and being a part of their oncology care team to live well after they’ve had treatment for cancer.

    Concluding Question
    Thank you for your time here today in the PodMD studio. To sum up for us, could you please identify the three key take home messages from today’s podcast on ovarian cancer?

    Rhett: The three key messages I’d like listeners to take away are that one ovarian cancer often presents in a subtle and non specific manner. Two, have a high index of suspicion for the diagnosis in. Women who present with abdominal, particularly gastrointestinal symptoms. And three, have a low threshold to investigate them further with a pelvic ultrasound and potentially a CT abdomen and pelvis.

    Thanks for your time and the insights you’ve provided.

    Rhett: Thank you

*As always, all in this PODMD podcast is intended for health professionals and the comments are of a general nature. Information given is not intended as specific medical advice pertaining to any given patient. If you have a clinical issue with one of your patients please seek appropriate advice from a colleague with expertise in the area.