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Cervical Cancer TABLE 8. International Federation of Gynecology and Obstetrics Cervical Cancer Staging and Treatment Stage Treatment |: Carcinoma is strictly confined to the cervix IA and IB: Modified radical (for lesions <2 cm) or radical hysterectomy with pelvic lymph node dissection is preferred; if IA: Microscopic disease only, up to 5 mm in depth poor functional status, irradiation can be used instead. IB: Clinically visible disease, or microscopic disease >5 mm If treated with surgery, adjuvant irradiation or chemoradiation is added if indicated based on final pathology. Fertility preservation surgery is an option for cancers <2 cm with no lymph node metastases. IA: Simple hysterectomy, cone biopsy (conization), or removal of cervix (trachelectomy) are options. IIA and IIB: Cervical carcinoma invades beyond the uterus, but not IIA: Same as for stage | to the pelvic wall or lower third of the vagina. IIB has parametrial IIB: Same as forstage Ill | invasion. Ill: The tumor extends to the pelvic wall, involves the lower third of Ill: Irradiation with concurrent platinum-based chemotherapy the vagina, causes hydronephrosis or nonfunctioning kidney, and/or involves the pelvic or para-aortic lymph nodes.

IIA and IIB: Cervical carcinoma invades beyond the uterus, but not IIA: Same as for stage | to the pelvic wall or lower third of the vagina. IIB has parametrial IIB: Same as forstage Ill | invasion. Ill: The tumor extends to the pelvic wall, involves the lower third of Ill: Irradiation with concurrent platinum-based chemotherapy the vagina, causes hydronephrosis or nonfunctioning kidney, and/or involves the pelvic or para-aortic lymph nodes. IV: The carcinoma extends beyond the true pelvis or involves the IVA: Same as for stage Ill mucosa of the bladder or rectum. IVB: Palliative cisplatin-based chemotherapy, with irradiation for IVA: Spread to adjacent organs local symptoms, such as bleeding or pain. Pembrolizumab is approved for second-line treatment in patients with programmed IVB: Distant metastases death ligand 1—positive tumors.

IV: The carcinoma extends beyond the true pelvis or involves the IVA: Same as for stage Ill mucosa of the bladder or rectum. IVB: Palliative cisplatin-based chemotherapy, with irradiation for IVA: Spread to adjacent organs local symptoms, such as bleeding or pain. Pembrolizumab is approved for second-line treatment in patients with programmed IVB: Distant metastases death ligand 1—positive tumors. United States is 48 years. During the last 30 years, cervical chemistry tests, kidney function studies, and imaging studies cancer incidence and deaths in developed countries have for moderate- and high-risk stage cancers. HIV testing should decreased by more than 50%, primarily because of screening be considered. Cervical cancer staging and treatment are and preventive treatment. It remains the second most com- described in Table 8. For patients with tumors 2 cm in size or mon cause of mortality from cancer in women worldwide. smaller that are confined to the cervix and with no lymph More than 85% of deaths are in less developed countries. node involvement, fertility-sparing surgeries such as coniza- Human papillomavirus (HPV) is the causative agent in tion (only for stage IA) or radical trachelectomy, in which the most patients and can be detected in 99.7% of cervical cancers. cervix and upper vagina are removed but the uterine corpus is Risk factors include earlier onset of sexual activity and having preserved, are options. several partners. Immunosuppression, including HIV infec- tion, low socioeconomic status, smoking, and oral contracep- e Early cervical cancer is frequently asymptomatic, but tive use are additional risk factors. Squamous cell carcinoma is the most common symptoms are abnormal or heavy the histologic type in 69% of cervical cancers, with adenocar- vaginal bleeding or vaginal discharge; advanced cervical cinoma accounting for 25%. HPV vaccination markedly cancer symptoms include pelvic or back pain and bowel decreases the incidence of cervical dysplasia and cervical can- cer. Cervical cancer screening and HPV vaccination are cov- or bladder symptoms.

United States is 48 years. During the last 30 years, cervical chemistry tests, kidney function studies, and imaging studies cancer incidence and deaths in developed countries have for moderate- and high-risk stage cancers. HIV testing should decreased by more than 50%, primarily because of screening be considered. Cervical cancer staging and treatment are and preventive treatment. It remains the second most com- described in Table 8. For patients with tumors 2 cm in size or mon cause of mortality from cancer in women worldwide. smaller that are confined to the cervix and with no lymph More than 85% of deaths are in less developed countries. node involvement, fertility-sparing surgeries such as coniza- Human papillomavirus (HPV) is the causative agent in tion (only for stage IA) or radical trachelectomy, in which the most patients and can be detected in 99.7% of cervical cancers. cervix and upper vagina are removed but the uterine corpus is Risk factors include earlier onset of sexual activity and having preserved, are options. several partners. Immunosuppression, including HIV infec- tion, low socioeconomic status, smoking, and oral contracep- e Early cervical cancer is frequently asymptomatic, but tive use are additional risk factors. Squamous cell carcinoma is the most common symptoms are abnormal or heavy the histologic type in 69% of cervical cancers, with adenocar- vaginal bleeding or vaginal discharge; advanced cervical cinoma accounting for 25%. HPV vaccination markedly cancer symptoms include pelvic or back pain and bowel decreases the incidence of cervical dysplasia and cervical can- cer. Cervical cancer screening and HPV vaccination are cov- or bladder symptoms. ered in General Internal Medicine 2. ¢ Select patients with cervical cancer confined to the cervix can be treated with surgery that preserves fertility. e Human papillomavirus is the causative agent in most e Patients with bulky or locally advanced cervical cancer patients with cervical cancer, and vaccination signifi- are treated with cisplatin-based chemotherapy and cantly reduces the risk. radiation instead of surgery.

ered in General Internal Medicine 2. ¢ Select patients with cervical cancer confined to the cervix can be treated with surgery that preserves fertility. e Human papillomavirus is the causative agent in most e Patients with bulky or locally advanced cervical cancer patients with cervical cancer, and vaccination signifi- are treated with cisplatin-based chemotherapy and cantly reduces the risk. radiation instead of surgery. Diagnosis, Staging, and Treatment Prognosis and Surveillance Patients with early cervical cancer are frequently asympto- The 5-year relative survival for all stages of cervical cancer is matic. The most common symptoms are abnormal or heavy 67.5%. The anatomic stage is the most important predictor of vaginal bleeding or vaginal discharge. Pelvic or back pain and prognosis. Ninety percent of patients with localized disease bowel or bladder symptoms are symptoms of advanced dis- survive 5 years. The 5-year survival rate drops to 58% for ease. Diagnosis is made by direct biopsy of a visible lesion, patients with regional disease and 17% for patients with disease colposcopy, or cone biopsy (conization). Current guidelines for extending outside of the true pelvis or involving the bladder or staging studies recommend a complete blood count, liver rectum. 16

Gastroenterological Malignancies Surveillance is recommended to monitor for recurrences synonymous. All CRCs should be screened for dMMR or MSI. that are potentially curable. Guidelines recommenda history Approximately 20% of patients with GMMR tumors will have a and physical examination every 3 to 6 months for 2 years, every germline mismatch repair deficiency, known as Lynch syn- 6 to 12 months during years 3 to 5, and then annually based on drome, which is discussed in Gastroenterology and Hepatology. the risk of recurrence. Annual vaginal cytology, cervical cytol- Lynch syndrome is autosomal dominant, and patients and fam- ogy, or both is recommended. Imaging and laboratory studies ily members should be offered formal genetic counseling and are recommended only if indicated based on symptoms or more intense cancer surveillance. Mismatch repair status of the findings on examination that are suspicious for recurrence. tumor can affect treatment choices in patients with stage II or stage IV cancer as discussed in the information to follow. HVC e Annual cervical or vaginal cytology should be done on all cervical cancer survivors; additional surveillance e Tumors arising on the right side of the large intestine have imaging and laboratory studies for cervical cancer sur- a different biology and substantially worse prognosis than vivors are recommended only if there are signs or tumors on the left side. symptoms suggestive of recurrence. e All colorectal cancers should be screened for mismatch repair enzyme deficiency or microsatellite instability; patients whose tumors test positive should be screened for Gastroenterological germline mismatch repair deficiency (Lynch syndrome). Malignancies Staging

HVC e Annual cervical or vaginal cytology should be done on all cervical cancer survivors; additional surveillance e Tumors arising on the right side of the large intestine have imaging and laboratory studies for cervical cancer sur- a different biology and substantially worse prognosis than vivors are recommended only if there are signs or tumors on the left side. symptoms suggestive of recurrence. e All colorectal cancers should be screened for mismatch repair enzyme deficiency or microsatellite instability; patients whose tumors test positive should be screened for Gastroenterological germline mismatch repair deficiency (Lynch syndrome). Malignancies Staging Colorectal Cancer TNM cancer staging is the first step in treatment planning (Table 9). Evaluation includes obtaining carcinoembryonic Colorectal cancer (CRC), the fourth most common cancer and antigen (CEA) levels in addition to routine laboratory studies; second leading cause of cancer death in North America, is a full colonoscopy (if possible); and contrast-enhanced CT largely preventable through screening. Current guidelines rec- scans of the chest, abdomen, and pelvis. Patients with rectal ommend routine screening to begin at age 50 years, although cancers also require a rectal MRI, which provides greater pre- the percentage of cases diagnosed below the age of 50 has cision in assessing tumor penetration and lymph node involve- increased from 10% to 12% over the past decade. CRC screening ment. PET scans do not provide greater accuracy in staging of average-risk patients is discussed in General Internal and should not be used unless contrast-enhanced CT scans are Medicine 2. Most colon cancers are adenocarcinomas that contraindicated. begin in the inner lining and progress to involve or spread beyond the full thickness of the bowel wall, to regional lymph Treatment nodes, and subsequently to distant organ metastases. Rectal Cancer Epidemiology, pathophysiology, risk factors, screening, and Rectal cancers that do not penetrate the full thickness of the clinical manifestations will be discussed in Gastroenterology bowel wall and do not involve regional lymph nodes are stage and Hepatology. I and are treated with surgical resection. Small stage I tumors Tumors on the midgut-derived right side of the large intestine (cecum, ascending colon, and proximal two thirds of transverse colon) have a markedly different biology, including TABLE 9. Staging of Colorectal Cancer

Colorectal Cancer TNM cancer staging is the first step in treatment planning (Table 9). Evaluation includes obtaining carcinoembryonic Colorectal cancer (CRC), the fourth most common cancer and antigen (CEA) levels in addition to routine laboratory studies; second leading cause of cancer death in North America, is a full colonoscopy (if possible); and contrast-enhanced CT largely preventable through screening. Current guidelines rec- scans of the chest, abdomen, and pelvis. Patients with rectal ommend routine screening to begin at age 50 years, although cancers also require a rectal MRI, which provides greater pre- the percentage of cases diagnosed below the age of 50 has cision in assessing tumor penetration and lymph node involve- increased from 10% to 12% over the past decade. CRC screening ment. PET scans do not provide greater accuracy in staging of average-risk patients is discussed in General Internal and should not be used unless contrast-enhanced CT scans are Medicine 2. Most colon cancers are adenocarcinomas that contraindicated. begin in the inner lining and progress to involve or spread beyond the full thickness of the bowel wall, to regional lymph Treatment nodes, and subsequently to distant organ metastases. Rectal Cancer Epidemiology, pathophysiology, risk factors, screening, and Rectal cancers that do not penetrate the full thickness of the clinical manifestations will be discussed in Gastroenterology bowel wall and do not involve regional lymph nodes are stage and Hepatology. I and are treated with surgical resection. Small stage I tumors Tumors on the midgut-derived right side of the large intestine (cecum, ascending colon, and proximal two thirds of transverse colon) have a markedly different biology, including TABLE 9. Staging of Colorectal Cancer a substantially worse prognosis, from those rising on the Stage Description Approximate

Colorectal Cancer TNM cancer staging is the first step in treatment planning (Table 9). Evaluation includes obtaining carcinoembryonic Colorectal cancer (CRC), the fourth most common cancer and antigen (CEA) levels in addition to routine laboratory studies; second leading cause of cancer death in North America, is a full colonoscopy (if possible); and contrast-enhanced CT largely preventable through screening. Current guidelines rec- scans of the chest, abdomen, and pelvis. Patients with rectal ommend routine screening to begin at age 50 years, although cancers also require a rectal MRI, which provides greater pre- the percentage of cases diagnosed below the age of 50 has cision in assessing tumor penetration and lymph node involve- increased from 10% to 12% over the past decade. CRC screening ment. PET scans do not provide greater accuracy in staging of average-risk patients is discussed in General Internal and should not be used unless contrast-enhanced CT scans are Medicine 2. Most colon cancers are adenocarcinomas that contraindicated. begin in the inner lining and progress to involve or spread beyond the full thickness of the bowel wall, to regional lymph Treatment nodes, and subsequently to distant organ metastases. Rectal Cancer Epidemiology, pathophysiology, risk factors, screening, and Rectal cancers that do not penetrate the full thickness of the clinical manifestations will be discussed in Gastroenterology bowel wall and do not involve regional lymph nodes are stage and Hepatology. I and are treated with surgical resection. Small stage I tumors Tumors on the midgut-derived right side of the large intestine (cecum, ascending colon, and proximal two thirds of transverse colon) have a markedly different biology, including TABLE 9. Staging of Colorectal Cancer a substantially worse prognosis, from those rising on the Stage Description Approximate hindgut-derived left side (distal third of the transverse colon, 5-Year Disease- Free Survival descending colon, sigmoid colon, and rectum). Left-sided tumors are more likely to cause a change in bowel habits. Tumor does not invade the full 90%-95% thickness of bowel wall (T1, T2); Cancers in the proximal colon rarely cause obstructive symp- lymph nodes not involved (NO) toms due to the wider lumen and liquid nature of the fecal Il Tumor invades full thickness of | 70%-85% contents. Patients with right-sided tumors are more likely to the bowel and may invade into present with iron-deficiency anemia due to occult, chronic pericolonic or perirectal fat (T3,

hindgut-derived left side (distal third of the transverse colon, 5-Year Disease- Free Survival descending colon, sigmoid colon, and rectum). Left-sided tumors are more likely to cause a change in bowel habits. Tumor does not invade the full 90%-95% thickness of bowel wall (T1, T2); Cancers in the proximal colon rarely cause obstructive symp- lymph nodes not involved (NO) toms due to the wider lumen and liquid nature of the fecal Il Tumor invades full thickness of | 70%-85% contents. Patients with right-sided tumors are more likely to the bowel and may invade into present with iron-deficiency anemia due to occult, chronic pericolonic or perirectal fat (T3, blood loss. Patients with colon cancer at any location may also TA); lymph nodes not involved (NO) present with hematochezia, pain, or acute clinical signs from Il One or more lymph nodes 25%-70% obstruction, or in rare cases, perforation. involved with cancer (N1, N2); Approximately 15% of CRCs lack one or more mismatch any T stage repair enzymes and are known as deficient mismatch repair IV Metastatictumorspreadtoany 0%-10% (dMMR) CRC, manifesting as increased microsatellite instabil- distant site or peritoneal | ity (MSI) in the cancer cell’s DNA and resulting in a condition metastases (M1); any T stage; any N stage of hypermutability; the terms GMMR and MSI are essentially

blood loss. Patients with colon cancer at any location may also TA); lymph nodes not involved (NO) present with hematochezia, pain, or acute clinical signs from Il One or more lymph nodes 25%-70% obstruction, or in rare cases, perforation. involved with cancer (N1, N2); Approximately 15% of CRCs lack one or more mismatch any T stage repair enzymes and are known as deficient mismatch repair IV Metastatictumorspreadtoany 0%-10% (dMMR) CRC, manifesting as increased microsatellite instabil- distant site or peritoneal | ity (MSI) in the cancer cell’s DNA and resulting in a condition metastases (M1); any T stage; any N stage of hypermutability; the terms GMMR and MSI are essentially 17