Epithelial Ovarian Cancer Flashcards
Ovarian Cancer
Sporadic or Non-Hereditary Ovarian Cancer
Most common type, accounting for 85-90% of all ovarian cancers in the United States
Ovarian Cancer
Familial and Hereditary Syndromes
Less Common, account for 10-15% of all ovarian cancers
- Familial ovarian cancer: The lifetime risk of a woman developing ovarian cancer increases by 50% if she has two or more first degree relatives with ovarian cancer
- Ovarian cancer occurs in 5-10% of women known to have hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome, or other rare genetic syndromes
Ovarian Cancer
BRCA1, BRCA2, TP53
Mutations = Play role in approximately 5-10% of ovarian cancers
Deletions
= BRCA1 deletion results in a 39-58% absolute risk of developing ovarian cancer
= BRCA2 deletion rsults in 13-29% absolute risk
Ovarian Cancer
EPITHELIAL ADENOCARCINOMA (90% of cases)
Types
- Serous (70%) - most common
- Endometrioid (10%)
- Clear Cell (10%) - associated with poor prognosis
- Mucinous (3%)
Ovarian Cancer
SCREENING
Currently no effective method of screening for ovarian cancer and routine screening is not recommended
Routine screening is not recommended for asymptomatic, low-risk patients
Ovarian Cancer
PREVENTION
Oral Contraceptives
- Use of Oral Contraceptives for five or more years may decrease risk of ovarian cancer by up to 50%
- Longer the use, greater the protection
- Protection may persist for up to 30 years following cessation
- WARNING - Oral contraceptives may increase risk of Breast Cancer
Ovarian Cancer
PREVENTION
Surgery
- Prophylactic risk-reducing salpingo-oophorectomy (RRSO) decreases the risk of ovarian cancer in high-risk patients including those with BRCA mutations, hereditary breast ovarian cancer (HBOC) syndrome, or moderate penetrance gene variations (e.g., BRIP1, RAD51C, RAD51D).
- NOT recommended for LOW RISK (cardiovascular benefit of ovaries)
- NOT protective against risk of developing primary peritoneal carcinoma
Ovarian Cancer
EARLY STAGE (I and II)
Initial Surgical Management
- Stage I (FERTILITY DESIRED)
Stage I (FERTILITY DESIRED)
- Stage IA - Unilateral salpingo-oophorectomy (preserving the uterus and contralateral ovary) and comprehensive surgical staging
- Stage IB - BSO (preserving the uterus) and comprehensive surgical staging
Ovarian Cancer
EARLY STAGE (I and II)
Initial Surgical Management
- Stage I (NO FERTILITY DESIRED)
Stage I-II (NO FERTILITY DESIRED)
- Total abdominal hysterectomy (TAH)/BSO, omentectomy, pelvic
and para-aortic lymph node sampling, appendectomy, peritoneal biopsies, cytologic washings, complete abdominal exploration and intact tumor removal if possible.
Ovarian Cancer
EARLY STAGE
Treatment - SUMMARY
- Stage IA or IB (grade 1 and 2 or low-grade serous)
- Grade 1 or low-grade serous: surgical staging followed by observation. Survival for these patients is > 90% with surgery alone.
- Grade 2 (non-serous): surgical staging followed by observation or platinum-based chemotherapy for 3-6 cycles.
Ovarian Cancer
EARLY STAGE
Treatment - SUMMARY
- Stage IA or IB (grade 3 or high-grade serous)
Stage IA or IB (grade 3 or high-grade serous)
Platinum-based chemotherapy consisting of:
- **Taxane (paclitaxel or docetaxel) or Liposomal Doxorubicin **
PLUS
- Carboplatin administered intravenously for 3-6 cycles (6 cycles are recommended for high-grade serous)
- Early stage ovarian cancer and serous histology had significantly lower risk of recurrence when treated with 6 cycles
Ovarian Cancer
EARLY STAGE
Treatment - Regimen
- Stage IA or IB (grade 1 and 2 or low-grade serous)
- < 70 years of age and no major comorbidities
- Paclitaxel 175 mg/m2 IV over 3 hours followed by carboplatin AUC 5-6 IV over 1 hour on day 1 every 3 weeks (preferred)
- Docetaxel 60-75 mg/m2 IV over 1 hour followed by carboplatin AUC 5-6 IV over 1 hour on day 1 every 3 weeks
- Carboplatin AUC 5 IV + pegylated liposomal doxorubicin 30 mg/m2 IV on day 1 every 4 weeks
Ovarian Cancer
EARLY STAGE
Treatment - Regimen
- Stage IA or IB (grade 1 and 2 or low-grade serous)
- > 70 years of age and/or major comorbidities
- Paclitaxel 135 mg/m2 IV over 3 hours followed by carboplatin AUC 5 IV over 1 hour on day 1 every 3 weeks
- Carboplatin AUC 5 IV on day 1 every 3 weeks
- Paclitaxel 60 mg/m2 IV over 1 hour followed by carboplatin AUC 2 IV over 30 minutes on day 1, 8, 15 every 3 weeks
Ovarian Cancer
EARLY STAGE
Treatment
- Stage II
-** Platinum-based chemotherapy for 6 cycles as is recommended in stage III-IV disease**
Ovarian Cancer
ADVANCED STAGE
Treatment - Surgical
- Stage III and IV
Comprehensive surgical staging for all patients as in early stage (includes TAH/BSO, omentectomy, lymph node sampling if no bulky disease, peritoneal biopsies)
- Optimal cytoreduction: < 1 cm residual disease following surgery (historically defined as < 2 cm, relevant with respect to historical literature)
- Suboptimal cytoreduction: > 1 cm residual disease following surgery
Ovarian Cancer
ADVANCED STAGE
Treatment - Adjuvant Chemotherapy
- Stage III and IV
- Platinum-based chemotherapy with a taxane (paclitaxel or docetaxel) and carboplatin IV
- Liposomal doxorubicin and carboplatin IV
- Paclitaxel and cisplatin administered IV/IP
TOTAL OF 6 CYCLES
Ovarian Cancer
ADVANCED STAGE
Considerations for Intraperitoneal therapy
- Stage III and IV
All appropriate patients be counseled about the clinical benefit and associated risks with IV and IP treatment before undergoing surgery.
HR for death was reduced if pt received IP component of therapy
Greater toxicity for IP component of therapy (GI, Pain, Fever, Infection)
Ovarian Cancer
ADVANCED STAGE
Appropriate Candidates for Intraperitoneal therapy
- Optimally cytoreduced stage II-III disease.
- Good performance status
- Normal renal function at baseline
- No relevant pre-existing comorbidities (e.g., peripheral neuropathy)
- No history of prior bowel surgery or rectosigmoid bowel resection at time of primary therapy
Ovarian Cancer
ADVANCED STAGE
Intraperitoneal Therapy - TOXICITIES
Significant toxicities of IP therapy include:
- infection
- leukopenia
- fatigue
- nausea
- renal toxicity
- neurotoxicity
- dehydration electrolyte abnormalities
- catheter malfunction
- abdominal pain
Ovarian Cancer
ADVANCED STAGE
Intraperitoneal Therapy - TOXICITIES
Modifications to dosage and delivery of IP
- Paclitaxel: administration over 3 hours (instead of 24 hours, as studied) to reduce myelosuppression and facilitate outpatient administration.
- Cisplatin: reduce dose to 75 mg/m2 (instead of 100 mg/m2 as studied) to reduce likelihood of severe renal/metabolic abnormalities