Gynaecological and Testicular Cancers: Platinum, PARP and Hormones

Ovarian cancer: the "platinum" disease

Every treatment conversation in ovarian cancer starts with one word: platinum. After surgery, the chemotherapy backbone for epithelial ovarian cancer is a platinum agent — usually carboplatin — combined with a taxane, paclitaxel. Carboplatin is an alkylating-like drug that forms cross-links in tumour DNA, and paclitaxel freezes the cell's microtubules so it cannot divide; the mechanisms themselves belong to the Oncology chapters on platinum chemotherapy and the taxanes, and we lean on them here rather than re-teach them. What matters clinically is a single concept that governs the whole disease: platinum sensitivity. A tumour that relapses more than six months after platinum is "platinum-sensitive" and can be treated with platinum again; one that relapses sooner is "platinum-resistant" and carries a far worse outlook. That one distinction drives every later decision.

The modern advance: PARP-inhibitor maintenance

Getting a good response to platinum was never the problem in ovarian cancer — keeping it was. The breakthrough of the last decade is maintenance therapy: after chemotherapy has done its work, a drug is continued to hold the disease down. The star is the PARP inhibitor — olaparib, niraparib — and it is the textbook example of targeted, synthetic-lethal therapy. Cells repair DNA by several parallel routes. PARP handles single-strand breaks; the BRCA-driven homologous-recombination pathway handles double-strand breaks. Block PARP with a drug, and single-strand damage collapses into double-strand breaks. A normal cell shrugs — its BRCA pathway fixes them. But a BRCA-mutant tumour cell has already lost that back-up, so the unrepaired damage is lethal. Two survivable defects become one fatal combination only inside the cancer cell — the essence of synthetic lethality, taught in full in the Oncology chapter on PARP inhibitors.

The other maintenance tool is an anti-angiogenic antibody. Alongside PARP inhibitors, bevacizumab — a monoclonal antibody against VEGF — is used both with chemotherapy and as maintenance. Tumours need to grow their own blood supply; bevacizumab starves that angiogenesis, and its VEGF mechanism (and its class side effects — hypertension, proteinuria, impaired wound healing, bowel perforation) belong to the Oncology chapter on anti-angiogenic therapy. The practical point is that the choice of maintenance is now biomarker-driven. This is why BRCA and HRD (homologous-recombination-deficiency) testing has become mandatory in ovarian cancer: a BRCA-mutant or HRD-positive tumour gains the most from a PARP inhibitor, whereas an HR-proficient tumour leans more on bevacizumab. Genotype, not just histology, now selects the drug.

Endometrial cancer: the oestrogen-driven tumour

The commonest gynaecological cancer in the developed world is endometrial (uterine) cancer, and its most important type is fundamentally hormonal. The endometrium grows under oestrogen and is restrained by progesterone; anything that gives the lining oestrogen without opposing progesterone — obesity (fat converts androgens to oestrogen), anovulation, unopposed oestrogen HRT, and tamoxifen (an oestrogen antagonist in breast tissue but a partial agonist on the uterus) — drives it toward cancer. This is the through-line to the Menopause and Endometriosis chapters, where the same oestrogen/progestogen balance and the paradoxical uterine effect of tamoxifen are covered from the hormone side; here we simply apply them. Treatment is surgery-led, but the pharmacology is squarely hormonal: progestogens (such as medroxyprogesterone or a levonorgestrel intrauterine system) oppose oestrogen's growth signal and can control low-grade disease — used for fertility-sparing treatment in a young woman who wants to conceive, or to palliate advanced disease.

For advanced or recurrent endometrial cancer, the field has moved into immunotherapy. A checkpoint inhibitor — pembrolizumab — is now standard, and it works especially well in tumours that are mismatch-repair-deficient (MMR-deficient / MSI-high), because those tumours are studded with mutations and highly visible to T cells. For mismatch-repair-proficient disease, pembrolizumab is combined with lenvatinib, an oral multi-kinase (anti-VEGF) inhibitor. The checkpoint mechanism and its immune-related adverse events sit in the Oncology chapter on checkpoint inhibitors; the biomarker logic — testing MMR/MSI status to choose immunotherapy — is exactly the tissue-agnostic principle taught there.

Cervical cancer: the vaccine-preventable cancer

The most important drug in cervical cancer is one you give before the cancer exists. Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HPV), chiefly types 16 and 18. That single fact makes it the great public-health story of gynaecological oncology: HPV vaccination, given before exposure, prevents the infection that causes the cancer — a genuine cancer vaccine. Alongside cervical screening, it is on course to make cervical cancer rare. The vaccine itself is covered in the Prevention/immunisation material (cross-linked from the Dermatology and public-health chapters, since HPV also drives anogenital and oropharyngeal disease). When cancer does develop, the mainstay for locally advanced disease is chemoradiation, where cisplatin is given not to kill the tumour outright but as a radiosensitiser — a low weekly dose that makes the radiotherapy far more effective. For advanced or recurrent cervical cancer, systemic therapy adds bevacizumab (anti-VEGF) and, increasingly, a checkpoint inhibitor (pembrolizumab) — the same two targeted principles seen throughout this chapter.

Testicular cancer: the great chemo-curable tumour

If one solid tumour proves that chemotherapy can cure, it is the testicular germ-cell cancer of young men. Even with metastatic spread to the lungs and lymph nodes, the majority are cured — an outcome that transformed oncology's ambitions. The regimen is BEP: bleomycin, etoposide and cisplatin. Cisplatin is again the anchor, cross-linking tumour DNA; etoposide is a topoisomerase-II inhibitor; bleomycin causes DNA strand breaks. What makes germ-cell tumours so treatable is their exquisite platinum sensitivity, and their course can be tracked with remarkable precision using tumour markers — AFP (alpha-fetoprotein), beta-hCG and LDH — which rise with the tumour and fall as treatment works, guiding both diagnosis and response. The mechanistic detail of each cytotoxic sits in the Oncology chemotherapy chapters; here the message is the pattern — platinum + curability + marker-guided care.

One drug in the regimen carries a signature, dose-limiting danger. The name to remember for its toxicity is bleomycin, because it can cause pulmonary fibrosis — progressive, sometimes irreversible scarring of the lungs. It is cumulative-dose related, worse with age, renal impairment and high inspired oxygen, and it means a cured young man may need lifelong caution (for example, warning anaesthetists to avoid high-concentration oxygen in future surgery). It is a defining example of an anticancer drug whose limiting toxicity is not the marrow but a specific organ — and a favourite exam link to the respiratory chapter.

Trophoblastic disease and fertility preservation

A rarer but instructive tumour is gestational trophoblastic disease — cancer arising from placental tissue after a molar or other pregnancy. It shares testicular cancer's happy trait of being intensely chemosensitive: low-risk disease is often cured with single-agent methotrexate, an antifolate that blocks dihydrofolate reductase and DNA synthesis. Methotrexate's mechanism and its rescue with folinic acid are taught in the Inflammation section (where the same drug, at far lower dose, treats rheumatoid arthritis) — another instance of applying a familiar drug in a new setting. hCG is the perfect tumour marker here, tracking response almost in real time.

Because these cancers strike people of reproductive age and their cures are cytotoxic, fertility preservation is a GU-specific duty, not an afterthought. Chemotherapy — especially alkylating agents — is gonadotoxic, damaging ovarian reserve and sperm production. So before treatment, the standard is to offer sperm cryopreservation for men and oocyte or embryo cryopreservation for women. During chemotherapy, a GnRH agonist may be given to suppress the ovaries into a quiescent, prepubertal-like state, which appears to offer some protection against ovarian damage — an application of the same GnRH physiology and agonist "flare-then-downregulation" pharmacology taught in the Endocrine and Menopause chapters. The principle is simple and humane: cure the cancer, but protect the possibility of a future family.