Regarding prognostic and predictive factors in epithelial ovarian cancer, all of the following statements are correct EXCEPT:

Explanation

## Analysis of Prognostic Factors in EOC ### Statement D: CA-125 as 'Single Most Important' Prognostic Factor **Key Point:** While CA-125 elevation correlates with disease burden and is useful for monitoring, it is NOT the single most important prognostic factor in EOC. Multiple factors carry greater independent prognostic weight. ### Hierarchy of Prognostic Factors in EOC | Factor | Prognostic Impact | Level of Evidence | |--------|------------------|-------------------| | **Stage** (FIGO) | Strongest independent predictor | Very high | | **Residual disease after surgery** | Critical for OS | Very high | | **Histologic grade** | Strong (especially HGSOC vs LGSOC) | High | | **BRCA/HRD status** | Predicts chemotherapy + PARP response | High | | **CA-125 level** | Reflects disease burden; prognostic but not primary | Moderate | | **Performance status** | Affects treatment tolerance | Moderate | **High-Yield:** FIGO stage and extent of residual disease after cytoreduction are the two strongest independent prognostic factors — not CA-125 alone. ### Why Other Statements Are Correct **Statement A (BRCA Mutations and Treatment Response):** - BRCA1/BRCA2 carriers show superior response to platinum-based chemotherapy (higher pathologic complete response rates) - BRCA-mutant tumours are exquisitely sensitive to PARP inhibitors (olaparib, rucaparib) due to homologous recombination deficiency - Median OS is often longer in BRCA-mutant EOC when treated with platinum + PARP inhibitor maintenance [cite:SOLO-1 trial] **Statement B (HGSOC vs LGSOC Prognosis):** - HGSOC accounts for ~70% of EOC and has significantly worse prognosis (5-year OS ~40% stage III–IV) - LGSOC is chemotherapy-resistant but slower-growing; better initial prognosis but poorer response to standard therapy - This distinction is fundamental to EOC classification and treatment strategy **Statement C (HRD Status vs BRCA Alone):** - HRD (homologous recombination deficiency) encompasses BRCA mutations, BRCA-like (BRCAness), and other DNA repair defects - HRD status is MORE predictive of PARP inhibitor response than BRCA mutation status alone - ~50% of BRCA-wild-type EOCs are HRD-positive and respond to PARP inhibitors - The SOLO-2 trial demonstrated PARP benefit in BRCA-mutant patients; the PAOLA-1 trial extended benefit to HRD-positive patients regardless of BRCA status **Clinical Pearl:** CA-125 is a tumour marker for monitoring response and recurrence, not a primary prognostic determinant. Staging, cytoreduction quality, and molecular features (BRCA/HRD) drive prognosis and treatment decisions. **Mnemonic: "SHRP" — Stage, Histology, Residual disease, Performance status** — these four outweigh CA-125 in prognostic importance.