A 48-year-old woman with relapsed ovarian cancer (platinum-sensitive, 18 months after first-line carboplatin-paclitaxel) presents with rising CA-125 and new pelvic masses on imaging. She is being considered for second-line chemotherapy. Her baseline labs show: WBC 6.8 × 10⁹/L, Hb 10.5 g/dL, platelets 185 × 10⁹/L, creatinine 0.9 mg/dL, normal liver function. What is the most appropriate next step in management?

Explanation

## Clinical Context This patient has platinum-sensitive relapsed ovarian cancer (recurrence >12 months after first-line platinum therapy). She is a candidate for platinum re-challenge, but modern management requires assessment of homologous recombination deficiency (HRD) status and BRCA mutation status to guide optimal second-line therapy. ## Key Point: **Before re-challenging with carboplatin, obtain HRD/BRCA status.** This determines whether to add a PARP inhibitor (olaparib, rucaparib) or bevacizumab to carboplatin, or to use PARP inhibitor monotherapy if HRD-positive and platinum-resistant. ## High-Yield: **Platinum-sensitive relapsed ovarian cancer (PSROC) management algorithm:** | Finding | Recommended Approach | |---------|---------------------| | HRD-positive (BRCA or genomic HRD) | Carboplatin + PARP inhibitor, OR PARP inhibitor monotherapy | | HRD-negative, platinum-sensitive | Carboplatin + bevacizumab ± paclitaxel | | Platinum-resistant | Pegylated liposomal doxorubicin, gemcitabine, or PARP inhibitor (if HRD-positive) | ## Clinical Pearl: The SOLO-2 and ARIEL3 trials demonstrated that PARP inhibitors significantly improve progression-free survival in platinum-sensitive relapsed ovarian cancer, especially in HRD-positive patients. This has become standard of care and must be assessed before chemotherapy selection. ## Mnemonic: **BRCA-HRD-PARP** — Before Re-Challenge with Alkylating agent, Homologous Recombination Deficiency status guides PARP inhibitor use. ## Why Option 1 is Wrong While carboplatin re-challenge is appropriate for platinum-sensitive disease, it must be paired with either bevacizumab (if HRD-negative) or a PARP inhibitor (if HRD-positive). Blind re-challenge without HRD assessment ignores current standard-of-care personalization. ## Why Option 2 is Wrong Bevacizumab monotherapy is not standard for platinum-sensitive relapsed ovarian cancer. It is typically combined with chemotherapy (carboplatin ± paclitaxel) or used as maintenance after chemotherapy. Avoiding alkylating agents entirely in a platinum-sensitive patient is suboptimal. ## Why Option 4 is Wrong Pegylated liposomal doxorubicin is reserved for platinum-RESISTANT relapsed ovarian cancer or when carboplatin re-challenge is contraindicated. This patient is platinum-sensitive and should be offered platinum-based re-challenge with appropriate targeted therapy (PARP inhibitor or bevacizumab based on HRD status).