Mucinous Ovarian Carcinoma Stage I G3 - chemo or not?

[cbulha]

I'm 40 years old and recently diagnosed with rare mucinous ovarian carcinoma stage 1A Grade 3, expansile subtype. I had total histerectomy, appendectomy, etc, on 5 February 2019. Doctors are divided about advising chemotherapy and I must make a decision, as I've done first cycle on 19 March (Oxaliplatin and Capecitabin) and next one was postponed until 29 April, so I can gather more information to make a decision. Can you share your experience and shed a light on whether I should continue chemotherapy treatment? Many thanks. Claudia

[Lindaura]

Dear Claudia,

I did not know very much about your cancer, but I do applaud your desire to learn and to do some research before accepting treatment. You prompted me to do some also:

My research has shown that your doctors are following a well documented and intelligent approach and that you are in good hands. Chemotherapy after surgery to remove all signs of cancer gives a better long term outcome than surgery alone.

Here is part of an article from the USA National Institute of Health, addressing your situation and the link to the entire article.

Best wishes,

Laura

ncbi.nlm.nih.gov/pmc/articl...

Early-stage ovarian cancer:

When and what type of adjuvant chemotherapy is indicated.

The prognosis of early-stage ovarian cancer is good.

2014 FIGO ovarian, fallopian tube, and peritoneal cancer staging system and corresponding TNM.

Tumour removal and adequate surgical staging, followed in most cases by adjuvant chemotherapy, represent the primary treatment for early-stage ovarian cancer [6]. Nonetheless, despite adequate frontline treatment, the risk of relapse is not negligible. The rationale of adjuvant chemotherapy after complete removal of the disease and adequate surgical staging is to eradicate any residual microscopic deposits of cancer cells responsible of potential recurrence of disease. Even if a number of evidences point to an advantage of adjuvant chemotherapy in early-stage ovarian cancer, the optimal regimen, and duration is still debated.

A Cochrane meta-analysis assessed the survival advantage of adjuvant chemotherapy in early-stage ovarian cancer [10]. Five randomised clinical trials were included in the analysis. The earliest three trials recruited a small number of patients and lacked enough events to demonstrate a possible impact of adjuvant treatment. On the contrary, the ICON1 and the ACTION trial [11] included a larger number of patients and had a sufficient power to demonstrate a treatment effect. These two trials randomised patients with serous, mucinous, endometrioid, clear-cell, and undifferentiated ovarian carcinomas to receive platinum-based chemotherapy or no chemotherapy [11]. The five-year and the updated 10-year overall survival rate was significantly better for women receiving adjuvant chemotherapy compared with the control group. Similar findings were reported for progression-free survival [10].

Additionally, these two trials address the question of which patients with early-stage ovarian cancer benefitted most from adjuvant chemotherapy. The ICON1 trial stratified patients in low/medium risk (FIGO-stage Ia G1-G2 or FIGO-stage Ib/Ic G1) and high risk (FIGO-stage Ia G3, Ib/Ic G2-G3, any clear cell). Both overall and progression-free survival were better in high-risk patients, but no difference was observed among treated and non-treated low–medium risk patients at five- and 10-year follow-up [12]. One of the limitations of this study is represented by an unclear indication for surgical staging, resulting in suboptimally staged patients. Conversely, the ACTION trial strongly recommended a complete surgical staging and planned a subgroup analysis on suboptimally and optimally staged patients. Patients with FIGO Stage-Ia/Ib G2–G3, FIGO Stage-Ic/IIa were included. Among the suboptimally staged women, adjuvant chemotherapy increased the overall and disease-free survival, whereas in the optimally staged patients, no difference was observed between the treated group and the control group. At a median follow-up of 10 years earlier, data were confirmed [10]. These results suggested that there is a subgroup of patients at good prognosis that apparently do not benefit from adjuvant chemotherapy. In particular, it is hypothesised that chemotherapy impacts only on occult disease in suboptimally staged patients. Nonetheless, a benefit in optimally staged tumour cannot be excluded.

In summary, adjuvant chemotherapy may be avoided for low-risk, optimally staged, Stage-I patients (FIGO Stage-Ia/Ib, G1–G2); chemotherapy is indicated after surgery for patients with high-risk Stage-I disease (FIGO Stage-Ic, G3). In case of suboptimal surgical staging of low-risk Stage-I patients, benefits and effect of adjuvant chemotherapy should be discussed with each individual patient [6, 7, 10].

No sound evidences that a combination of carboplatin plus paclitaxel for early-stage disease is superior to carboplatin alone [13] are available. Studies that compare these two regimens are lacking [8]. Indirect suggestions of greater efficacy when combining carboplatin and taxanes are gathered by results in advanced stage disease. A well-designed trial is needed to identify the optimal chemotherapy regimen in this patient population. In the absence of clear recommendations, single-agent carboplatin seems a reasonable option for intermediate and high-risk early-stage ovarian cancer patients [13].

The optimal duration of adjuvant chemotherapy remains a matter of investigation. A randomised trial which compared three versus six cycles of platinum plus paclitaxel for early-stage ovarian cancer, revealed a 24% reduction in recurrence rate in patients who underwent six courses of chemotherapy [14]. A subgroup analysis stratifying patients on the basis of clinical and pathological features, showed a statistically significant benefit of six versus three cycles of chemotherapy only in serous tumours, while outcome for non-serous tumours was not influenced by the duration of chemotherapy [15]. Again, there may be a subgroup of patients who do not benefit from intensive adjuvant chemotherapy and future research is needed to confirm these hypotheses.

Clear cell, low-grade serous, mucinous or endometrioid ovarian cancers: Different therapeutic approaches for different neoplasms

The landscape of medical treatment of ovarian cancer has changed in the last years, thanks to improved biologic understanding. Beyond traditional chemotherapy, several target agents has been tested with the aim of improve outcome of patients with ovarian cancer. Angiogenesis play a role in promoting tumour growth and favouring metastasis. The antiangiogenetic agent bevacizumab improve progression-free survival in advanced stage and recurrent ovarian cancer, highlighting the importance of angiogenesis pathway in the tumour development. Phase-III studies are testing the efficacy of tyrosine kinase inhibitors, which target pro-angiogenesis proteins [16]. Promising results are obtained by antiangiogenetic therapy in epithelial ovarian cancers, independently by histological features. But molecular and genomic understanding suggests that key advancement in ovarian cancer treatment may be kept into the different spectrum of genomic aberrations that each ovarian cancer subtype displays.

[Petrolhead]

Hi Claudia

I was diagnosed with mucinous OC.

Not sure where you live as recommendations vary between countries.

In the UK adjuvant treatment is advised for 1C stage and above whether mucinous or otherwise. Below this watch and wait is the norm.

The combo you have done is usual in the US or Ireland.

Many in the U.K. have a single agent platinum drug for mucinous. (Capecitabine in your case). As you have probably gathered mucinous act differently to other OC and indeed DrGershensen at MD Anderson in the USA usually recommends The FOLFOX regime.

Certainly the fact that it is expansile rather than infiltrative is good ie on the surface of the ovary and not “infiltrating “ in the organ.

It may also depend on the level of monitoring that you negotiate after and that you are satisfied with.

Mine was stage 1C grade 1. As it was stage 1C I decided on adjuvant therapy. In the U.K. they would not offer adjuvant for stage 1a so no decision for us.

Not much help to you really but best of luck with your choice.

Best wishes

Fay

[cbulha in reply to Petrolhead]

Hi Fay

Thanks for sharing your experience.

I've had several discussions with doctors, so what I really need now is to speak to other who are going through the same and really understand how overwhelming this is...

I live in Portugal and I decided to be treated privately due to the urgency of the surgery (my gyn was worried it would take longer to have the surgery in the public hospital).

My gyn onc surgeon advises I should do chemo, but my oncologist doesn't agree, as a revision of an article in the New England Journal of Medicine about mucinous ovarian carcinomas, dated 28 March 2019, states that in mucinous cancers the distinction should not be on grade, but between growth patterns of invasion:

Expansile (confluent) Vs Infiltrative

According to my oncologist, the decision re treatment should be based on this, and since the diagnosis on the pathology report indicates my mOC is expansile, regardless of the grade, adjuvant chemotherapy is not advised (only in infiltrative subtypes).

I have now requested a review of the biopsy and just came now from the Oncology public hospital in Lisbon where I handed the 75 slides and 65 blocks for the pathologist there to analyse and review.

I'm gathering as much information as possible. I've also requested a second medical opinion from the team of doctors Advance Medical, who will share my case with international experts in the USA and Europe and they'll give me their views. I want to make sure I'm making a decision that I feel it's the right one for me, since I've been given the option.

Through a friend I got to have the opinion from MD Anderson, and their opinion was that if it was a well staged IA, then they wouldn't normally advise chemo, but considering the high grade, they would lean towards adjuvant chemotherapy as it would seem reasonable. They were also slightly confused that in my pathology report states the carcinoma was expansile, but at the same time G3 (rapid growth), so they said it was crucial for the report to be accurate. Hence, I'm applying for a review of the biopsy.

Hopefully I will receive results form review and second medical opinion before the 29 April, as I cannot put the chemotherapy treatment on standby for longer than this...

Thanks for being there.

Take care.

Claudia xx

[Petrolhead in reply to cbulha]

Hi Claudia

You have certainly done your homework and asked all the right questions. Never an easy job.

Certainly odd being expansile and rapid growth. Getting another opinion on the staging and grade very well worth it.

Not to be nosy but did you have a colonoscopy to rule out mets from the bowel?

Did your histology report mention K7 or K20 positivity?

I will be very interested in what you find out re second opinion etc.

Best of luck and keep us informed. You certainly seem to know how to go about finding the relevant info from the best people.

Best wishes

Fay

[cbulha in reply to Petrolhead]

Hi Fay

Thanks for keeping in touch

Please see also my reply to Emma with more info.

Re your queries (keep them coming, we're here to help eachother:), I haven't done a colonoscopy or endoscopy yet, as initially the advice right after surgery was chemo and those exams would be the next step... When I did the abdominopelvic MRI before surgery it showed all other organs were unaffected.

My histology report mentions:

CK7+ and CK20+focal

When were you diagnosed? Were you premenopausal? Did you have a full histerectomy? I am yet to come to terms with the surgical menopause, I'd rather take a step at a time...

Thanxx

Claudia

[Petrolhead in reply to cbulha]

Hi Claudia

Certainly seems to confirm primary. 🙂

I was post menopausal. (No menopause symptoms either when it happened) Had full op with everything taken in Sept 2016. (See my profile). I decided to have chemo because they did not do any abdominal washings after my op. If they had and it had shown no cancer cells then I might have gone for watch and wait. I had a second opinion at the Royal Marsden in London and went with their recommendations.

Best wishes

Fay

[JanTheHesitator in reply to Petrolhead]

Thanks Fay, I've recently been diagnosed with mucinous ovarian cancer and have been struggling to find any info. Especially since it seems to behave differently to other forms of OC. I'm in London, U.K.

[Petrolhead in reply to JanTheHesitator]

Hi Jan

If you private message me with a standard email address I can send you a couple of papers which give a lot of information. You are also welcome to ask me stuff and if I can answer I will.

I also suggest that you put mucinous in the search box as there have been a few threads on it here.

Best wishes

Fay

[Small_bump]

Hi, I'm sorry I don't know much about the different types of ovarian cancer (I'm still waiting for surgery and full diagnosis) but I have thought about this myself, whether I would have chemo if it was down to my choice etc. I think in your situation I probably would just so I would be more sure that all the cancer was gone for good, I'd be far too worried otherwise.

Good luck whichever route you decide to take,

Emma xxx

[cbulha in reply to Small_bump]

Hi Emma

Thanks for sharing your views.

My oncologist believes that doing chemo will only have a 1 or 2 % rate of success.

She said in my case there is already a 90% survival rate in 5 years, which is the best (unfortunately no chemo would raise this to 100%...). She told me that if I do the chemo it could be mainly for psychological reasons, that is, to make me feel better and cover everything to try to ensure it is gone, as you pointed out.

Just wanted to also mention that towards the end of my first chemo intravenous treatment, I had a serious allergic reaction to the toxicity of the Oxaliplatine and couldn't breathe for a couple of minutes (bronchospasm, it was similar to an anaphylactic shock). The nurses were alarmed as this is not a common reaction or side effect, but they promptly administered an injection of cortisone and dexamethasone and I was breathing normal again and as if nothing happened!! It was the strangest feeling ever.... As if I didn't have lungs at all!

Fortunately that didn't happen again and my side effects, even with the Capecitabine tablets were mild.

My oncologist said that it was indeed an unusual reaction (may happy to 5% of patients), but it can be controlled by prolonging the treatment duration and increase dosage of cortisone.

Anyway, sorry about the length of my reply, but I felt I needed to get this off my chest...

Thank You all for "listening".

Claudia xx

[Caroles1]

Hi Claudia,

I too was mucinous 1c and 6 months Chemo, carbo/taxol. I had my treatment at Harley Street.

My train of thought is, operation first, chemo after if at all possible.

I think it gives us the best chance. I am coming up to 5 years cancer free in September.

Wish you all the best with your decision

Carole xx

[Serengeti]

Dear ladies

I am not really replying to your question

I just want to share that I read a lot on OC

It seems not many researches give a definite answer

I even think that the Drs just do treatments randomly according to their experiences or some guidelines that are probably outdated .

At the end of most studies they will mention that results are not conclusive and biased .

The one paper I read that gave me a good picture was a research of why OC becomes agressive.

They found out that unlike other cancers OC tends to metastasize using the omentum and due to the soft tissue of omentum the cells become agressive

Basically I am guessing if the omentum is free of cancer cells then the cancer hasn’t spread.

Anyway all the best ladies

Xxx

[Hidden]

Dear Claudia

I was diagnosed with stage 1a grade 3 ovarian cancer 23 years ago and it is difficult making the decision about chemo - mine was a serous tumour. I wasn’t sure what to do but the question I asked myself was what would I feel if the cancer came back and I had decided not to have chemo. The answer to that will be different for everyone and given that there are no guarantees even having treatment, only you know what you feel.

I decided to have Carboplatin alone and I have been fine since, whether I would have been OK if I hadn’t had the chemo no one knows. Wishing you all the best as you make that decision

[cbulha]

Hi ladies!

I hope you're keeping well.

Just to give you na update on my request of Second Medical Opinion regarding whether I should continue or not my chemotherapy treatment.

For your info, see below (Google translation into English) the reply from an international specialist.

I'm still waiting for the review of the autopsy, but I'm leaning towards continuing chemotherapy treatment, especially based on the fact that it was grade 3.

"1. Should I do more exams?

In this situation, you need to perform a PET-CT to assess the presence of metastases.

It seems to me important to assess whether the tumor is of the "expansive" or "infiltrative" subtype.

Although controversial, some authorities still advocate removal of the appendix when there is a mucinous tumor, as about half comes from the gut. Therefore, if there is any doubt about the experience of the surgical team, it may be wise to consult a Gynecologic Oncologist for staging surgery and perform a colonoscopy.

CK7 + CK20 + tumors may originate from the gallbladder area and it may be useful to perform an MRI of the liver.

To conclude, Lynch syndrome may be a cause of ovarian tumors in young women, and we recommend that all people with an ovarian tumor perform a genetic test, and their tumor should be stained for the determination of IMS-E ( Microsatellite Instability - High) or MMR (mutations in the mismatch repair genes).

That said, all the most important things were done.

2. What is the best treatment in my current situation?

In general, the stage IA disease does not require chemotherapy.

Recently, some groups have advocated chemotherapy for the initial infiltrative-type mucinous tumors (NOT their type).

I was a Collaborative Research Fellow at the GOG 241, an international effort to try to find out the best therapy for patients with mucinous ovarian cancer, which are rare and, after all, only 50 patients were enrolled and therefore it is impossible to draw final conclusions, but the oxaliplatin and capecitabine appeared to be better than paclitaxel and carboplatin [Gore M, et al. An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC / GOG 0241) with long-term follow-up: and experience of conducting clinical trial in a rare gynecological tumor. Gynecol Oncol. April 17, 2019. pii: S0090-8258 (19) 30491-3]

There is an obvious and solid justification for intraperitoneal chemotherapy (administer chemotherapy directly into the abdominal cavity) and people have analyzed hyperthermia and chemotherapy and this has been done for years as Hyperthermia Intraperitoneal Chemotherapy (HIPEC). Generally, this is not recommended.

It is extremely important that the tumor has been completely removed. Congratulations, you do not need chemotherapy!

3. In this clinical situation, what is the prognosis?

There is a 94% chance of cure. This recent evaluation is excellent: Morice P, et al. Mucinous Ovarian Carcinoma. N Engl J Med. March 28, 2019; 380 (13): 1256-1266.

It is a common mistake to think that all mucinous tumors are aggressive. In fact, early-stage tumors have a better prognosis than serous tumor of the high-grade ovary.

Surviving with confidence, while living with a deadly disease, is a challenge, especially with cancer, a disease so talked about in the news and posing a great threat. You should be well informed, have good emotional support and always have a plan to deal with all the physical, emotional and existential challenges of cancer. Do not overweight and stay in good shape (strong, flexible, and energized). Eat plenty of antioxidants (cereals, fruit and fresh vegetables - broccoli, blueberries ...) as far as your gut allows, and have a positive mental attitude.

Surveillance of CA-125 is controversial because there is no indication of benefits and good indications that it triggers treatment and early reintroduction of chemotherapy, since relapse is associated with a lower quality of life. But as yours was high, we will monitor it.

It should be evaluated every 3 months for the first two years and then every 6 months for three years and then annually.

"