Neuroendocrine cancers of the gynaecological organs represent a diverse and relatively rare group of malignancies, each with unique characteristics and clinical behaviours. These cancers originate from neuroendocrine cells, which are distributed throughout the body and play a vital role in regulating hormonal and nervous system functions.
Unlike more common gynaecological cancers like those of the cervix, uterus, ovaries, vagina, and vulva, neuroendocrine cancers exhibit distinct biological features and diagnostic challenges. Their rarity necessitates specialised knowledge and care approaches to ensure accurate diagnosis, effective treatment, and appropriate follow-up.
This page serves as a comprehensive resource on neuroendocrine cancers of the gynaecological organs, offering insights into their epidemiology, symptoms, diagnostic methods, treatment options, and ongoing research efforts. Whether you’re seeking information for yourself, a loved one, or for professional knowledge, understanding these unique cancers is crucial for informed decision-making and supportive care management.
Cervical Neuroendocrine Cancer
Ovarian Neuroendocrine Cancer
Neuroendocrine Cancer of the Uterus
Overview
- The ovaries produce the female hormones oestrogen and progesterone, they are also responsible for the production and release of eggs into the Fallopian tubes at the mid-point of each menstrual cycle.
- The uterus is the shape of an upside down pear and sits within the pelvis, between the bladder and the bowel. It is where a foetus develops and grows during normal pregnancy.
- The cervix is a cylinder-shaped neck of tissue that connects the vagina and uterus (womb).
- The vagina allows for menstrual blood to flow out of the body from the uterus, it is also the ‘birth canal’.
- The vulva is the external female genitalia – it includes the clitoris and openings of both the vagina and urethra (the opening through which urine from the bladder is passed). There is a network of blood vessels and nerve pathways linking the uterus to the external genitalia, that play a role in sexual response and orgasm.
Neuroendocrine Cancers of the gynaecological organs range from the uncommon to incredibly rare, depending on site of origin.
Neuroendocrine Cancer of the Ovary affects approximately 30 women a year in the UK. They are usually secondary deposits from the bowel or appendix, but primary disease can occur.
Primary Neuroendocrine Cancers of the cervix and uterus are even rarer, with vaginal and vulval NENs the most rare – with only a handful of women, across the world, diagnosed each year.
Female Reproductive System
Causes and potential risk factors for Neuroendocrine Cancer
We do not know exactly what causes Neuroendocrine Cancer – however it is important to follow advice in leading a healthy lifestyle: eat healthily, exercise and avoid smoking and too much alcohol.
Most Neuroendocrine Cancers do not run in families; however, a number of rare conditions may increase the risk of them developing. Therefore, if other members of the family have been diagnosed with cancer, or have a known genetic condition, it is important that you tell your specialist team about not only your personal medical history, but also any family medical illnesses or conditions.
Most cases of ovarian cancer do not run in families, but genes known as BRCA1 and BRCA2 can increase your risk of developing both ovarian and breast cancer.
The genes TP53 and CHEK2, are also associated with an increased risk of breast cancer.
We recommend speaking to your GP, and specialist team, if ovarian or breast cancer runs in your family. They may refer you for an NHS genetic test, which will tell you if you have inherited one of the cancer-risk genes.
Neuroendocrine Cancers of the Cervix, Ovary, Uterus, Vagina and Vulva are very rare – and may not be associated with the above mentioned genetic alterations. However, if there is a strong family history of cancer or you do have a genetic alteration this may help inform your care and ensure follow up is appropriate for you.
And although HPV infection (HPV) may be very common and is considered a high risk factor for cervical cancer, cervical cancer itself is relatively uncommon. Widespread vaccination of both girls and boys against HPV is believed to have played a major role in reducing the development of cervical cancer.
Symptoms +/- Neuroendocrine associated Syndromes
(Syndrome is where 2 or more related symptoms occur).
Symptoms, if present, may be similar to those experienced by women with more common gynaecological cancers – diagnosis is usually made by histology review, following surgery or a biopsy.
Gynaecological cancer symptoms by site:
(Cervix, Ovary, Uterus, Vagina & Vulva):
- Unusual / Abnormal discharge : ALL sites
- Abnormal vaginal bleeding : ALL sites
- Early satiety – feeling full / constant bloating / ‘wind’ : Ovary
- Pelvic pressure or discomfort or pain : Ovary, Uterus or Vagina
- Abdominal (tummy) +/- Back pain : Ovary or Uterus
- Increased need to pee +/- constipation : Ovary or Vagina
- Itching/burning/tenderness of vagina/ vulva : Vagina or Vulva
- Lump +/- skin changes – rashes, warts, sores : Vagina or Vulva
- Pain during +/- Bleeding after sex : ALL sites
Neuroendocrine Cancer of the Gynaecological organs is rarely associated with a Neuroendocrine associated syndrome – however Carcinoid Syndrome has been reported.
Other, rarer symptoms, including Paraneoplastic syndrome and oncological emergencies, (a specific set of health concerns that can occur in any cancer), such as raised calcium levels (Hypercalcaemia), may occur.
Further information about Neuroendocrine Cancer associated and Paraneoplastic Syndromes – including Oncological emergencies – can be found here.
Tests that may be used for the diagnosis and / or monitoring of Neuroendocrine Cancer of the Cervix, Ovary, Uterus, Vagina and Vulva:
Blood and / or urine:
Full blood count
Liver and kidney function
B12/Iron/Ferritin/Folate
Chromogranin A
Gut hormone profile
Calcium
Thyroid function
LDH, Ca125, CEA
Urinary or serum 5HiAA (serotonin).
NT-Pro-BNP – to check for evidence of Carcinoid Heart Disease
Clinical assessment for presence of Carcinoid Syndrome and/or other paraneoplastic syndromes – Cushings, SIADH, Hypoglycaemia and Hypercalcaemia
Clinical assessment for possibility of pregnancy and/or menopause
Scans & further investigations:
Cervical smear
Pelvic +/- Transvaginal Ultrasound Scan
CT chest, abdomen and pelvis and/ or CT chest & MRI abdomen and pelvis
Octreotide (SPECT) or Gallium-Dotatate PET/CT.
FDG-PET – if NEC or rapidly progressing disease is suspected or seen
Bone scintigraphy – if bone disease is suspected or present
Echocardiogram – if evidence of Carcinoid Syndrome / raised Urinary 5HiAA / elevated Pro-NT-BNP or if there are clinical signs of R sided heart failure/valve impairment.
Pathology (what can be seen through special tests under a microscope):
Differentiation and cellular morphology
Synaptophysin
Chromogranin
Ki67
HPV18
CD56, PYY – optional
Exclude Merkel cell carcinoma in vaginal / vulval disease
The key aim of treatment, should be to help you have the best possible care and quality of life – by ensuring access to appropriate treatment, management of symptoms and addressing what’s most important to you.
Treatment options will depend on the type, position and size of your cancer – and whether (and to where) it has spread.
It will also depend on whether you have any other health concerns and / or illnesses and your general health and fitness.
One or more of the approaches below may be suggested:
- Surgery
- Control of your disease, by slowing or stopping further growth and / or spread
- Palliation, or easing, of any symptoms you may be experiencing.
Surveillance:
Monitoring through clinic review, bloods and scans, can be used to assess how well treatment is working or in periods between treatments (which may be months/years).
As not everyone will need to be on treatment – surveillance can be used to check your cancer and general health for any signs of change that may mean that a treatment might need to be considered. All treatments have possible side-effects, therefore, it is important to know when treatment may be helpful for you or not.
Surgery:
May be offered to remove the cancer and the nearby lymph nodes. There are many different types of surgery – depending on where the cancer is:
Cone biopsy:
Used in very early stage cervical cancer – a cone-shaped area of abnormal cervical tissue is removed during surgery.
Radical trachelectomy:
Used for early stage cervical cancer – it removes the cervix, upper third of the vagina, lower part of the uterus and pelvic lymph nodes.
Oopherectomy:
Removal of the one ovary or both (bilateral oophorectomy).
Salpingoopherectomy (SO):
Removal of the ovary and Fallopian tube – or both (bilateral salpingoopherectomy – BSO).
Vulval resection:
Removing some or all of the vulva +/- lymph nodes.
Vaginal resection:
Removing part or all of the vagina +/- lymph nodes
Sub-total hysterectomy:
Removal of the uterus.
Total abdominal hysterectomy (TAH):
Removal of the uterus and cervix.
TAH and BSO:
Removal of the uterus, cervix, both ovaries and the Fallopian tubes.
Wertheim’s (Radical) Hysterectomy:
Removal of the uterus, top of the vagina, Fallopian tubes, both ovaries, supporting tissues and lymph nodes.
Radical Hysterectomy with ovarian conservation:
Similar to Wertheim’s but leaving the ovaries.
Anterior pelvic exenteration:
emoval of all of the reproductive organs and the bladder.
Posterior pelvic exenteration:
Removal of all of the reproductive organs plus the bowel.
Total pelvic exenteration:
Involves removal of all of the reproductive organs, the bladder and bowel.
Non-surgical Treatments:
Somatostatin analogues (SSAs):
Can be used to help regulate the secretion of hormones if abnormal levels are being produced. SSAs may also be used to slow down growth rate in low to moderate grade ‘well-differentiated’ neuroendocrine cancer (NET).
Chemotherapy:
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size. This may be the first line therapy in high grade disease – particularly “poorly-differentiated’ NEC or in combination with other treatments. Chemotherapy may also be used to increase tumour cell sensitivity to radiation therapies.
Targeted Molecular Therapies:
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size.
Radiotherapy:
Is sometimes given after surgery to kill any cancer cells that might remain there. It may also be used for cancer that has spread beyond the breast in particular if disease has spread to the bones – here it is used to help control growth of any spread and alleviate bone pain.
Brachytherapy:
Is also known as internal radiotherapy. It uses a radioactive source (capsule) to treat cancer. This can damage all cells within the treatment area; killing the cancer cells but allowing your normal cells to recover. Used primarily in uterine or vaginal cancer.
Large loop excision of the transformation zone (LLETZ):
Where the cancerous cells are removed using a fine wire and an electrical current. It’s usually done under local anaesthetic (while you’re awake but the area is numbed) and can be done at the same time as a colposcopy.
Clinical Trials:
Clinical research and safe new treatment development is essential to provide best care for those with Neuroendocrine Cancer – we need to know that treatments not only work but work safely. There are several phases of trial therapy. Each trial will have specific criteria in regards to patient suitability – this can be discussed with your clinical team. You do not have take part in a trial – participation is voluntary.
Symptom Control:
Managing symptoms, including pain, is an important part of total care – and therefore occurs throughout care, not just at ‘end-of-life’. Symptom control or ‘palliation’ refers to what is used to alleviate or reduce the impact your cancer, other health issues and /or treatments may be having on you and your physical and mental health. It can include anything from simple medication and / or a combination of some of the treatments mentioned above to counselling and practical support.
There are expert agreed guidelines regarding how and when follow up should occur, however, in practice this varies and often with good reason. Follow up should be expert informed & evidence /research based but also tailored to you and what is appropriate for your best care.
There is no definitive agreement on the best post-treatment surveillance for Gynaecological Neuroendocrine Cancers, therefore care and follow up should be guided by histology, grading and staging, and potential for treatment – in association with guidelines produced by the British Gynaecological Cancer Society and the Royal College of Obstetricians and Gynaecologists.
Gynecological examination including PAP smear is usually performed every 3 months for the first 2 years, every 6 months for the next 3 years, and yearly thereafter.
Biomarkers as indicated / if elevated at diagnosis +/- if recurrence, metastatic disease develops.
CT or PET/CT scan should be performed as clinically indicated.
Advanced disease:
Follow up as per guidelines – but should be guided by prognosis, expected treatment efficacy and treatment related toxicity. Your health, well-being, physical activity, informed choice and preference for ongoing care as well as aim of treatment should be reviewed and discussed to best plan care.