Cancer Survivorship, Late Effects & Fertility Preservation

Survivorship care and surveillance

The survivorship care plan. When active treatment ends, the patient and primary care physician should receive a written summary of the diagnosis, every treatment with cumulative doses (anthracycline mg/m², radiation fields and dose), and a follow-up schedule. Late-effect screening follows these exposures, not the original diagnosis. Survivors still need age-appropriate cancer screening, vaccinations, smoking cessation, and exercise.

Recurrence surveillance fits the cancer. After resection of stage II–III colon cancer: history, exam, and CEA every 3–6 months for 2 years, then every 6 months to year 5; CT chest/abdomen/pelvis every 6–12 months for 5 years; colonoscopy 1 year after surgery (at 3–6 months if an obstructing tumor prevented a complete preoperative exam), then at 3 years and every 5 years. Breast cancer survivors need only history, exam, and annual mammography; tumor markers, CT, PET, and bone scans in asymptomatic patients do not improve survival.

Second malignancies

Therapy-related myeloid neoplasms. Both types carry a worse prognosis than de novo AML; unexplained cytopenias in a survivor call for a smear and marrow biopsy.

Breast cancer after chest radiation. Chest or mantle radiation (10 Gy or more, per COG) before age 30, classically for Hodgkin lymphoma, confers a breast cancer risk approaching that of BRCA carriers, greatest when developing breast tissue is exposed. Screen with annual mammography plus breast MRI from 8 years after radiation or age 25, whichever is later.

Other field cancers. Solid tumors appear 10 or more years later inside the field: papillary thyroid cancer, bone and soft-tissue sarcomas, basal cell and other skin cancers, and lung or GI cancers (lung risk multiplies in smokers).

Bladder cancer after cyclophosphamide. The metabolite acrolein causes acute hemorrhagic cystitis and a lasting rise in urothelial carcinoma; hematuria in a survivor warrants cystoscopy with upper-tract imaging.

Heart and lungs

Anthracycline cardiomyopathy. Doxorubicin and daunorubicin generate iron-dependent free radicals, causing dose-dependent, largely irreversible dilated cardiomyopathy that may surface years later: heart failure in about 5% at a cumulative doxorubicin dose of 400 mg/m², rising steeply beyond. Chest radiation, trastuzumab, age extremes, and preexisting heart disease add risk; dexrazoxane, an iron chelator, protects during treatment. Trastuzumab dysfunction, by contrast, is not dose-related and usually reversible. Survivors need periodic echocardiography and standard heart failure therapy if the ejection fraction falls.

Radiation heart disease. Mediastinal radiation (Hodgkin lymphoma, left-sided breast cancer) injures every layer of the heart 10–20+ years later: premature ostial and proximal coronary disease, thickened aortic and mitral valves with regurgitation or stenosis, constrictive pericarditis, and conduction block. Control blood pressure, lipids, glucose, and smoking aggressively, obtain periodic echocardiograms, and evaluate chest pain or dyspnea early.

Pulmonary fibrosis. Bleomycin (dose-related; worse with age, renal impairment, and radiation), busulfan, carmustine (sometimes years later), and chest radiation cause fibrosis; evaluate symptoms with PFTs including DLCO.

Flag prior bleomycin for anesthesia: high inspired oxygen has been linked to postoperative respiratory failure, so FiO₂ is kept as low as safely possible.

Endocrine, bone, nerves, and quality of life

Thyroid and pituitary. Neck or mantle radiation causes primary hypothyroidism in up to about half of Hodgkin survivors over decades, plus nodules and papillary cancer: check TSH (with free T4) yearly and palpate the gland. Cranial radiation damages the pituitary in a predictable order — GH, then LH/FSH, ACTH, and TSH last — so slowed growth is often the first sign in a child.

Gonads. Alkylators (cyclophosphamide, procarbazine, busulfan) and pelvic radiation cause premature ovarian insufficiency (amenorrhea, high FSH, low AMH), more readily in older women with a smaller oocyte reserve; give estrogen plus a progestin until about age 51 unless the cancer is hormone-sensitive. In men, germ cells fail before Leydig cells, so azoospermia with normal testosterone is common; higher doses cause Leydig failure needing testosterone.

Bone. Aromatase inhibitors (anastrozole, letrozole, exemestane), androgen deprivation (leuprolide), premature menopause, and glucocorticoids accelerate bone loss. Obtain a baseline DXA, repeat every 1–2 years, ensure calcium, vitamin D, and weight-bearing exercise, and add a bisphosphonate or denosumab for osteoporosis or high fracture risk while cancer therapy continues. Tamoxifen, a partial estrogen agonist on bone, preserves density after menopause.

Neuropathy. Platinums, taxanes, vincristine, and bortezomib cause stocking-glove sensory neuropathy that may persist (after cisplatin it can worsen for months, "coasting"); cisplatin also causes high-frequency hearing loss. Duloxetine has the best evidence for painful neuropathy.

Fatigue, cognition, and fear. For fatigue, the most common complaint, exclude anemia, hypothyroidism, hypogonadism, depression, insomnia, cardiac dysfunction, and sedating drugs; structured aerobic and resistance exercise is the best-proven treatment. Cognitive complaints ("chemo brain") and fear of recurrence are common: treat mood and sleep problems, screen for distress, and offer CBT and support.

Fertility preservation and contraception

Timing. Discuss fertility with every reproductive-age patient before gonadotoxic therapy and refer promptly; most options must be completed before the first dose.

Contraception. Confirm a negative pregnancy test and use effective contraception throughout therapy. Avoid estrogen, because cancer raises VTE risk; with current breast cancer all hormonal methods are contraindicated, so the copper IUD is preferred.

Amenorrhea during chemotherapy is not contraception: ovulation can resume unpredictably, and most cytotoxic drugs are teratogenic.