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Ovarian Cancer take place, focusing on their values and preferences as they are treated for an incurable illness. ¢ For women with BRCA1, BRCA2, or MMR gene muta- tions, prophylactic bilateral salpingo-oophorectomy is e Metastatic breast cancer is not curable, but it can be recommended after completion of childbearing. treated with systemic therapy with the goals of improved survival, symptom palliation, and maintaining quality of life. Diagnosis Patients with ovarian cancer usually present at an advanced e The site of initial metastasis should be biopsied to con- stage with bloating, abdominal or pelvic pain, constipation, firm the diagnosis and to assess hormone receptor and or early satiety. Initial evaluation should include a pelvic HER? status, which can be discordant from the primary examination, general physical examination, serum CA-125 breast cancer. level, complete blood count, liver chemistry tests, and trans- vaginal ultrasonography. Additional CT or MRI imaging are done as clinically indicated. Patients with a high suspicion Ovarian Cancer of ovarian cancer should be referred to a gynecologic oncologist. Epidemiology and Risk Factors For early ovarian cancer, surgical exploration is reeom- Risk factors for epithelial ovarian cancer include mutations of mended for diagnosis because removing the ovarian cancer ovarian cancer susceptibility genes, increasing age, infertility, intact without rupture improves survival. For advanced ovar-

Ovarian Cancer of ovarian cancer should be referred to a gynecologic oncologist. Epidemiology and Risk Factors For early ovarian cancer, surgical exploration is reeom- Risk factors for epithelial ovarian cancer include mutations of mended for diagnosis because removing the ovarian cancer ovarian cancer susceptibility genes, increasing age, infertility, intact without rupture improves survival. For advanced ovar- nulliparity, endometriosis, polycystic ovary syndrome, and ian cancers with peritoneal masses, ascites, or pleural effu- cigarette smoking. sions, fluid cytology or image-guided biopsy can be done, The most common ovarian cancer susceptibility genes are particularly if the disease is not initially resectable and neoad- BRCA1, BRCA2, and the mismatch repair (MMR) genes associ- juvant chemotherapy may be used. ated with Lynch syndrome. Approximately 10% to 15% of Staging and prognosis are shown in Table 7. Early stage, low grade, serous histology, extent of disease after surgical women with ovarian cancer carry a mutation in one of these genes, and all women with epithelial ovarian cancer should be debulking, and young age are associated with improved sur- offered germline genetic testing for BRCA1 and BRCA2 muta- vival. A total of 31% of patients diagnosed with ovarian cancer tions. In patients with a personal or family history of other survive 10 years, with one third of these long-term survivors Lynch syndrome cancers (e.g., colorectal cancer, cancer of the having stage III or IV cancer.

offered germline genetic testing for BRCA1 and BRCA2 muta- vival. A total of 31% of patients diagnosed with ovarian cancer tions. In patients with a personal or family history of other survive 10 years, with one third of these long-term survivors Lynch syndrome cancers (e.g., colorectal cancer, cancer of the having stage III or IV cancer. endometrium or small bowel, transitional cell carcinoma of the ureter or renal pelvis), MMR mutation testing is recommended as well. The cumulative lifetime risk of ovarian cancer is 45% in Treatment BRCAI carriers and 3% to 12% in the other gene mutation Surgical staging includes total hysterectomy, bilateral carriers. salpingo-oophorectomy, peritoneal washings, omentectomy, and pelvic and para-aortic lymph node sampling. Surgical

endometrium or small bowel, transitional cell carcinoma of the ureter or renal pelvis), MMR mutation testing is recommended as well. The cumulative lifetime risk of ovarian cancer is 45% in Treatment BRCAI carriers and 3% to 12% in the other gene mutation Surgical staging includes total hysterectomy, bilateral carriers. salpingo-oophorectomy, peritoneal washings, omentectomy, and pelvic and para-aortic lymph node sampling. Surgical debulking, including the resection of metastatic disease, e Genetic testing for BRCA1 and BRCA2 mutations should improves prognosis. The volume of residual disease after be offered to all women with ovarian cancer. surgery correlates inversely with survival. Neoadjuvant chemotherapy is recommended for patients with initially unresectable disease to shrink the tumor to facilitate surgical Risk-Reduction Strategies debulking. and Screening Patients with early-stage ovarian cancer who have favora- For women with BRCA1, BRCA2, or MMR gene mutations, pro- ble histology may be treated with surgical resection alone. phylactic bilateral salpingo-oophorectomy is recommended All other patients should receive adjuvant platinum-taxane after completion of childbearing. For BRCA1 or BRCA2 carriers, chemotherapy. When incorporated into systemic therapy, prophylactic bilateral salpingo-oophorectomy decreases the intraperitoneal chemotherapy has been shown to improve risk of ovarian cancers by greater than 80% and decreases all- survival in some trials, albeit with more toxicity, in women cause mortality to age 70 years by 77%. Recommendations for with stage III disease. genetic testing for breast and ovarian cancer syndromes are Women with advanced ovarian cancer and BRCA1 or discussed in Breast Cancer. BRCA2 mutations who achieve some response to traditional Ovarian cancer screening with transvaginal ultrasonogra- chemotherapy should receive subsequent maintenance ther- phy or serum CA-125 is not recommended for patients of aver- apy with olaparib, a poly (ADP-ribose) polymerase inhibitor. age risk and has no proven benefit even in women with Second-look laparotomy to assess pathologic response is high-risk genetic mutations. not beneficial.

debulking, including the resection of metastatic disease, e Genetic testing for BRCA1 and BRCA2 mutations should improves prognosis. The volume of residual disease after be offered to all women with ovarian cancer. surgery correlates inversely with survival. Neoadjuvant chemotherapy is recommended for patients with initially unresectable disease to shrink the tumor to facilitate surgical Risk-Reduction Strategies debulking. and Screening Patients with early-stage ovarian cancer who have favora- For women with BRCA1, BRCA2, or MMR gene mutations, pro- ble histology may be treated with surgical resection alone. phylactic bilateral salpingo-oophorectomy is recommended All other patients should receive adjuvant platinum-taxane after completion of childbearing. For BRCA1 or BRCA2 carriers, chemotherapy. When incorporated into systemic therapy, prophylactic bilateral salpingo-oophorectomy decreases the intraperitoneal chemotherapy has been shown to improve risk of ovarian cancers by greater than 80% and decreases all- survival in some trials, albeit with more toxicity, in women cause mortality to age 70 years by 77%. Recommendations for with stage III disease. genetic testing for breast and ovarian cancer syndromes are Women with advanced ovarian cancer and BRCA1 or discussed in Breast Cancer. BRCA2 mutations who achieve some response to traditional Ovarian cancer screening with transvaginal ultrasonogra- chemotherapy should receive subsequent maintenance ther- phy or serum CA-125 is not recommended for patients of aver- apy with olaparib, a poly (ADP-ribose) polymerase inhibitor. age risk and has no proven benefit even in women with Second-look laparotomy to assess pathologic response is high-risk genetic mutations. not beneficial. 14

Cervical Cancer TABLE 7. International Federation of Gynecology and Obstetrics Ovarian Cancer Staging, Treatment, and Survival Stage Definition Treatment 5-Year Survival Stage | disease (favorable)? Cancer in one or both ovaries, Surgery alone 94% overall survival not high grade or clear cell, negative peritoneal washings, no rupture Stage | disease (unfavorable); Unfavorable stage | disease: Surgery followed by 3 to 6 Stage |: 85% relative survival? stage || disease confined to ovaries but with cycles of chemotherapy Stage Il: 70%-78% relative high-grade or clear cell (usually carboplatin and survival histology, rupture, or positive paclitaxel) peritoneal washings Stage Il disease: soread beyond ovaries but confined to pelvis

Stage | disease (unfavorable); Unfavorable stage | disease: Surgery followed by 3 to 6 Stage |: 85% relative survival? stage || disease confined to ovaries but with cycles of chemotherapy Stage Il: 70%-78% relative high-grade or clear cell (usually carboplatin and survival histology, rupture, or positive paclitaxel) peritoneal washings Stage Il disease: soread beyond ovaries but confined to pelvis Optimally debulked stage III Spread to abdomen, with Surgery followed by IV or IV/IP IV chemotherapy: 40% overall disease residual tumor masses <1 cm chemotherapy survival after debulking surgery Maintenance olaparib after IV/IP chemotherapy: 50% first-line chemotherapy overall survival (23% decreased risk of death with IP/IV versus IV chemotherapy)

Optimally debulked stage III Spread to abdomen, with Surgery followed by IV or IV/IP IV chemotherapy: 40% overall disease residual tumor masses <1 cm chemotherapy survival after debulking surgery Maintenance olaparib after IV/IP chemotherapy: 50% first-line chemotherapy overall survival (23% decreased risk of death with IP/IV versus IV chemotherapy) Suboptimally debulked Stage Ill (suboptimal) disease: Surgery (usually done even for Stage Ill: 39% relative survival stage Ill disease or stage IV spread to abdomen with stage IV disease as it improves Stage IV: 17% relative survival disease® residual masses >1 cm after survival) and chemotherapy; debulking surgery preoperative (neoadjuvant) chemotherapy given for initially Stage IV disease: spread unresectable cancer beyond abdomen Maintenance olaparib after first-line chemotherapy

Suboptimally debulked Stage Ill (suboptimal) disease: Surgery (usually done even for Stage Ill: 39% relative survival stage Ill disease or stage IV spread to abdomen with stage IV disease as it improves Stage IV: 17% relative survival disease® residual masses >1 cm after survival) and chemotherapy; debulking surgery preoperative (neoadjuvant) chemotherapy given for initially Stage IV disease: spread unresectable cancer beyond abdomen Maintenance olaparib after first-line chemotherapy | IP =intraperitoneal; IV = intravenous. *Careful staging is critical: almost one third of patients with apparent early disease will have more advanced disease when thorough staging is completed. Relative survival is the ratio of the proportion of observed survivors in a cohort of patients with cancer to the proportion of expected survivors in a comparable set of cancer-free | individuals. “According to recent guidelines by the American Society of Clinical Oncology and the Society of Gynecologic Oncology, patients with stage IIIC or IV ovarian cancer who are at high perioperative risk or who have a low likelihood of optimal tumor debulking should receive neoadjuvant chemotherapy followed by reevaluation for cytoreductive surgery.

“According to recent guidelines by the American Society of Clinical Oncology and the Society of Gynecologic Oncology, patients with stage IIIC or IV ovarian cancer who are at high perioperative risk or who have a low likelihood of optimal tumor debulking should receive neoadjuvant chemotherapy followed by reevaluation for cytoreductive surgery. 6 months or more after initial chemotherapy are considered to have platinum-sensitive disease, have a better prognosis, and e Patients with stage I ovarian cancer with favorable his- are usually treated with platinum-containing combination tology may be treated with surgery alone; all other chemotherapy. Adding the angiogenesis inhibitor bevaci- patients should receive platinum-taxane chemotherapy. zumab to combination chemotherapy improves disease-free HVC e Second-look laparotomy to assess pathologic response survival but increases the risk of serious gastrointestinal tox- following chemotherapy of ovarian cancer should not icities. For patients with platinum-resistant disease, various be performed. single agents can be used.

6 months or more after initial chemotherapy are considered to have platinum-sensitive disease, have a better prognosis, and e Patients with stage I ovarian cancer with favorable his- are usually treated with platinum-containing combination tology may be treated with surgery alone; all other chemotherapy. Adding the angiogenesis inhibitor bevaci- patients should receive platinum-taxane chemotherapy. zumab to combination chemotherapy improves disease-free HVC e Second-look laparotomy to assess pathologic response survival but increases the risk of serious gastrointestinal tox- following chemotherapy of ovarian cancer should not icities. For patients with platinum-resistant disease, various be performed. single agents can be used. Monitoring and Follow-up e Patients who relapse more than 6 months after discon- tinuing platinum-based chemotherapy for ovarian Posttreatment surveillance consists of physical and pelvic cancer are considered to have platinum-sensitive examinations every 3 to 6 months for 5 years, then annually. disease and should be treated with platinum-based Surveillance of CA-125 levels may indicate early tumor pro- combination chemotherapy. gression but does not have an impact on survival. Other testing is recommended only to evaluate symptoms or findings sug- gesting recurrence.

Monitoring and Follow-up e Patients who relapse more than 6 months after discon- tinuing platinum-based chemotherapy for ovarian Posttreatment surveillance consists of physical and pelvic cancer are considered to have platinum-sensitive examinations every 3 to 6 months for 5 years, then annually. disease and should be treated with platinum-based Surveillance of CA-125 levels may indicate early tumor pro- combination chemotherapy. gression but does not have an impact on survival. Other testing is recommended only to evaluate symptoms or findings sug- gesting recurrence. Cervical Cancer Management of Recurrent Epidemiology and Risk Factors Ovarian Cancer In the United States, approximately 13,000 new patients are Despite optimal treatment, 80% to 85% of women with stage diagnosed with invasive cervical cancer per year, and about Ill or IV ovarian cancer will relapse. Patients who relapse 4200 deaths are reported. The mean age of diagnosis in the 15