Follow up after cancer treatment is essential
|All AYA cancer survivors should have access to systematic long-term follow-up of their reproductive, endocrine and sexual health.||B|
The follow-up process
The scheduling and commencement of post-treatment follow up depends on the type of cancer and treatment and the needs of the individual patient. Some survivors have little or no post-treatment issues; others will need more regular monitoring by a multidisciplinary team of specialists and referral for psychological support.
Generally, monitoring and screening should commence and continue according to evidence-based recommendations for the particular cancer and treatment. An example is the Childrens Oncology Group (COG) long-term follow-up guidelines for survivors of childhood and AYA cancers.
- The first fertility review and assessment of reproductive, endocrine and sexual health should take place approximately six months after treatment is finished.
- A long-term schedule for follow up should be developed according to the patient’s age, cancer, treatment and risks of late effects.
- Follow up should be conducted by a multidisciplinary team including a fertility specialist, where possible.
Effective long-term follow-up of AYA patients requires good communication between paediatric and adult services and the patient’s GP and other health care providers. There should be clear referral pathways and communication with appropriate specialties such as endocrinology, gynaecology and assisted reproduction. Women who have gone through premature (<40 years) or early (<45 years) menopause due to cancer treatment should also be followed up by a menopause specialist.
Follow up may be shared care (if appropriate) with a central designated coordinator. This may be completed at yearly late effects/long-term follow up clinic assessments.
Depending on the patient’s age, fertility status and personal circumstances, discussion at each follow up appointment may include advice about contraception, assisted reproduction, alternative parenting options, sexual health issues, health behaviours, family planning and menopause management.
Patients should be given printed materials or referred to educational websites, and offered referral to specialist psychological support and to fertility, endocrine or other specialists as required.
Fertility may be temporarily or permanently affected by cancer treatment. Hence it is imperative to review fertility and assess reproductive function after treatment ends.
The first assessment after the completion of treatment should include:
- a review of patient history
- physical assessment including:
- for males: Tanner staging and testicular volume (Prader orchidometry)
- for females: breast assessment (clinical) and pelvic ultrasound (as appropriate)
- semen analysis (males) or assessment of menstrual history (females)
- analysis of reproductive hormones
- endocrine assessment (as appropriate - e.g. thyroid function, prolactin)
- assessment of sexual function.
Amenorrhea or menstrual history is often used as a measure of ovarian function. But assessment of ovarian reserve or function also should include:
- early follicular phase serum FSH
- serum antimullerian hormone (AMH)
- ultrasound assessment of ovarian volume
- ultrasound assessment of antral follicle count 
An assessment of ovarian reserve should be done about six months after treatment ends (or 12 months after BM/SC transplant). But adequate hormone replacement should be implemented earlier as required, especially for transplant patients.
Even if seemingly normal menses has resumed in AYA patients after cancer treatment, an earlier menopause may occur, ovarian follicle numbers may be reduced and markers of ovarian reserve reduced (FSH, AMH, inhibin B and LH).
For males, hormonal assessment including serum FSH can indicate whether there is a significant defect in spermatogenic function.
If the patient preserved sperm or oocytes, follow up analysis reports to inform them of the likely success of the cryopreservation.
Patients with high risk disease, for whom fertility preservation was not possible before treatment began, should be referred to an endocrinologist or fertility specialist to assess fertility and discuss options for sperm or oocyte collection. However the value of referral depends on the cancer. For example, patients who have had conditioning therapy for BMT are unlikely to have adequate residual ovarian function to consider oocyte collection.
Monitoring after transplant
Resumption of spontaneous fertility, in particular ovarian function, after bone marrow transplant occurs at least temporarily in about 10 to 20 percent of patients. Post-transplant fertility is related to the specific conditioning regimen and the age of the patient at the time of transplant. However it is not predictable.
Recommendations for monitoring of ovarian function and hormone replacement vary and should be guided by expert opinion. All female AYAs of reproductive age should be referred to a specialist gynaecologist for assessment of hormone function, consideration of hormone replacement and assessment for genital tract graft versus host disease.
Recovery of spermatogenesis may occur in some males post transplant. This depends on dose and type of transplant treatment, as well as the risk of sterilisation of any previous treatment. Semen analysis is recommended 12 months after transplant, and hormone analysis of FSH, LH and testosterone at 6, 12 and 24 months.
General endocrine assessment
Ongoing endocrine related assessment after cancer treatment should include monitoring of thyroid function and bone densitometry as well as vitamin D levels.
Development of thyroid nodules secondary to treatment, particularly radiotherapy, may be a risk factor for hypothyroidism. This may have an impact on successful conception in females with preserved fertility. In addition it may contribute to other general health concerns including obesity, hypertension and diabetes.
The late effects of chest radiation including increased risks of breast and thyroid cancer should be considered during follow up.
Sexual health assessment and education
Independent of fertility and endocrine assessment, survivors of AYA cancers should be monitored for sexual health issues and concerns. It is estimated that at least 20% of cancer survivors experience sexual dysfunction, due to physiological and/or psycho-sexual factors.
Male survivors may experience erectile dysfunction and impaired libido. Physical changes and altered body image also can impact psycho-sexual function.
Survivors may have impaired hormone production as a direct result of treatment (chemotherapy +/- radiotherapy +/- HSCT/CBT) or disease site-specific factors (e.g. testicular cancer, pituitary tumours). Surgical intervention such as retroperitoneal lymph node dissection may result in interruption to nerve supply, impacting on sexual function.
The literature is sparse on sexual health issues for AYAs after cancer treatment. However research with adult survivors suggests sexual health education and assessment including advice regarding contraception, health behaviours and monitoring for dysfunction as a result of treatment, is an essential part of long term follow up and screening. AYAs, even if infertile, must be advised of the importance of using barrier contraception to reduce the risk of sexually transmitted disease.
- Children's Oncology Group. Long-term follow-up guidelines for survivors of childhood, adolescent and young adult cancers. Version 3.0. 2008.
- Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol 2006 Jun 20;24(18):2917-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16651642.
- Reulen RC, Zeegers MP, Wallace WH, Frobisher C, Taylor AJ, Lancashire ER, et al. Pregnancy outcomes among adult survivors of childhood cancer in the British Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev 2009 Aug;18(8):2239-47 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19661083.
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- Bath LE, Wallace WH, Shaw MP, Fitzpatrick C, Anderson RA. Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Mullerian hormone, inhibin B and ovarian ultrasound. Hum Reprod 2003;18:2368-2374.
- van Beek RD, van den Heuvel-Eibrink MM, Laven JS, de Jong FH, Themmen AP, Hakvoort-Cammel FG, et al. Anti-Mullerian hormone is a sensitive serum marker for gonadal function in women treated for Hodgkin's lymphoma during childhood. J Clin Endocrinol Metab 2007 Oct;92(10):3869-74 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17726078.
- Grigg AP, McLachlan R, Zaja J, Szer J. Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg). Bone Marrow Transplant 2000 Nov;26(10):1089-95 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11108308.
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- Peate M, Meiser B, Hickey M, Friedlander M. The fertility-related concerns, needs and preferences of younger women with breast cancer: a systematic review. Breast Cancer Res Treat 2009 Jul;116(2):215-23 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19390962.