Browse the corpus

Answers and Critiques Item 1 Answer: B Item 2 Answer: A Educational Objective: Treat cancer in a patient with Educational Objective: Evaluate a patient with gross reversible poor performance status. hematuria while taking an anticoagulant.

Item 1 Answer: B Item 2 Answer: A Educational Objective: Treat cancer in a patient with Educational Objective: Evaluate a patient with gross reversible poor performance status. hematuria while taking an anticoagulant. The most appropriate management is fluorouracil and oxal- This patient requires prompt referral to a urologist for cys- iplatin (Option B). This patient has advanced metastatic toscopy (Option A) in the evaluation of unexplained gross adenocarcinoma of the colon and a debilitated performance hematuria. Hematuria is defined as the presence of 23 eryth- wn status; however, it is clear that the debilitation is due to tumor rocytes/hpf in the urine sediment and may be microscopic a s burden in an otherwise medically fit individual. The patient, (detectable only on urine testing) or macroscopic (grossly = previously well and active with no comorbid medical condi- visible). A single incidental finding of hematuria is sufficient 7 tions, developed a rapid decline in health associated with the to warrant further investigation. Evaluation should be pur- cs) sc onset of tumor-related symptoms. This is the sort of situation sued even in patients with bleeding diatheses, or in those < in which aggressive management with combination chemo- taking antiplatelet or anticoagulation therapy. If menstru- c wn therapy (fluorouracil and oxaliplatin) is indicated. Only a ation, viral illness, vigorous exercise, or some other benign st o major response to chemotherapy has the potential to reverse cause is suspected, urinalysis should be repeated after the = ~” the debilitation, and if the tumor does respond to treat- cause is resolved. If infection is confirmed, urinalysis should = << ment, the patient’s performance status is expected to improve be repeated after treatment to document resolution of hema- toward her precancer, healthy state. This is a marked contrast turia. Although CT urography (contrast CT with kidney- to a patient who is severely debilitated by a combination of a specific imaging) has the highest sensitivity and specificity cancer with heavy tumor burden associated with precancer for renal malignancy, noncontrast helical CT is more appro- comorbidities that reduced performance status before devel- priate if a kidney stone is suspected. Ultrasonography is a opment of the cancer. reasonable first imaging step because of availability, lower Single-agent, low-dose chemotherapy (Option A) cost, and no ionizing radiation. Cystoscopy is indicated when would be insufficient in terms of a meaningful impact on imaging results are negative. reducing tumor burden and improving performance status. Discontinuing rivaroxaban and choosing warfarin Nonmetastatic colon cancers are managed with initial (Option C) as an alternative anticoagulant is not appropri- surgery. Pathologic evaluation determines further treatment. In ate. Gross hematuria requires a thorough evaluation regard- patients with metastatic colon cancer, surgery on the primary less of the use of anticoagulant therapy. Finally, there is tumor (Option C) is unnecessary in the absence of obstruction no evidence that warfarin is any safer than rivaroxaban in and would delay the start of needed chemotherapy. preventing hematuria. In a patient with serious preexisting comorbidities The American College of Physicians and the American that limited performance status before the development of Urological Association recommend against obtaining urine cancer—especially if there is concurrent kidney or hepatic cytology (Option D) in the initial evaluation of hematuria dysfunction—supportive care and hospice management due to poor sensitivity. (Option D) would be recommended. However, all indications Reassurance without additional intervention (Option E) suggest that this patient’s disability is directly related to the or repeating a urinalysis (Option B) is not appropriate, as a effects of the tumor, and improvement in functional status and single episode of gross hematuria should trigger an evalu- quality of life is expected with combination chemotherapy. ation for the cause.

The most appropriate management is fluorouracil and oxal- This patient requires prompt referral to a urologist for cys- iplatin (Option B). This patient has advanced metastatic toscopy (Option A) in the evaluation of unexplained gross adenocarcinoma of the colon and a debilitated performance hematuria. Hematuria is defined as the presence of 23 eryth- wn status; however, it is clear that the debilitation is due to tumor rocytes/hpf in the urine sediment and may be microscopic a s burden in an otherwise medically fit individual. The patient, (detectable only on urine testing) or macroscopic (grossly = previously well and active with no comorbid medical condi- visible). A single incidental finding of hematuria is sufficient 7 tions, developed a rapid decline in health associated with the to warrant further investigation. Evaluation should be pur- cs) sc onset of tumor-related symptoms. This is the sort of situation sued even in patients with bleeding diatheses, or in those < in which aggressive management with combination chemo- taking antiplatelet or anticoagulation therapy. If menstru- c wn therapy (fluorouracil and oxaliplatin) is indicated. Only a ation, viral illness, vigorous exercise, or some other benign st o major response to chemotherapy has the potential to reverse cause is suspected, urinalysis should be repeated after the = ~” the debilitation, and if the tumor does respond to treat- cause is resolved. If infection is confirmed, urinalysis should = << ment, the patient’s performance status is expected to improve be repeated after treatment to document resolution of hema- toward her precancer, healthy state. This is a marked contrast turia. Although CT urography (contrast CT with kidney- to a patient who is severely debilitated by a combination of a specific imaging) has the highest sensitivity and specificity cancer with heavy tumor burden associated with precancer for renal malignancy, noncontrast helical CT is more appro- comorbidities that reduced performance status before devel- priate if a kidney stone is suspected. Ultrasonography is a opment of the cancer. reasonable first imaging step because of availability, lower Single-agent, low-dose chemotherapy (Option A) cost, and no ionizing radiation. Cystoscopy is indicated when would be insufficient in terms of a meaningful impact on imaging results are negative. reducing tumor burden and improving performance status. Discontinuing rivaroxaban and choosing warfarin Nonmetastatic colon cancers are managed with initial (Option C) as an alternative anticoagulant is not appropri- surgery. Pathologic evaluation determines further treatment. In ate. Gross hematuria requires a thorough evaluation regard- patients with metastatic colon cancer, surgery on the primary less of the use of anticoagulant therapy. Finally, there is tumor (Option C) is unnecessary in the absence of obstruction no evidence that warfarin is any safer than rivaroxaban in and would delay the start of needed chemotherapy. preventing hematuria. In a patient with serious preexisting comorbidities The American College of Physicians and the American that limited performance status before the development of Urological Association recommend against obtaining urine cancer—especially if there is concurrent kidney or hepatic cytology (Option D) in the initial evaluation of hematuria dysfunction—supportive care and hospice management due to poor sensitivity. (Option D) would be recommended. However, all indications Reassurance without additional intervention (Option E) suggest that this patient’s disability is directly related to the or repeating a urinalysis (Option B) is not appropriate, as a effects of the tumor, and improvement in functional status and single episode of gross hematuria should trigger an evalu- quality of life is expected with combination chemotherapy. ation for the cause. e Inthe treatment of cancer, it is important to differen- e A single incidental finding of hematuria is sufficient tiate patients with a poor performance status who are to warrant investigation into its cause. debilitated due to chronic precancer comorbidities e Evaluation of hematuria should be pursued even in from patients who would otherwise be medically fit patients with bleeding diatheses or those taking anti- but are acutely debilitated by their cancer. platelet or anticoagulation therapy.

e Inthe treatment of cancer, it is important to differen- e A single incidental finding of hematuria is sufficient tiate patients with a poor performance status who are to warrant investigation into its cause. debilitated due to chronic precancer comorbidities e Evaluation of hematuria should be pursued even in from patients who would otherwise be medically fit patients with bleeding diatheses or those taking anti- but are acutely debilitated by their cancer. platelet or anticoagulation therapy. Bibliography Bibliography Kullmann T, Gauthier H, Serrate C, et al. To treat or not to treat metastatic Nielsen M, Qaseem A; High Value Care Task Force of the American College cancer patients with poor performance status: a prospective experience. of Physicians. Hematuria as a marker of occult urinary tract cancer: Pathol Oncol Res. 2017;23:139-44. [PMID: 27605003] doi:10.1007/s12253- advice for high-value care from the American College of Physicians. Ann 016-O1l1-4 Intern Med. 2016;164:488-97. [PMID: 26810935] doi:10.7326/M15-1496 67

Arawere one Seuey Item 3 Answer: D Item 4 Answer: C Educational Objective: Avoid unnecessary imaging in a Educational Objective: Treat stage III colon cancer. patient with stage 0 to II invasive breast cancer. This patient has stage IIIB colon cancer, and the most appro- Patients with newly diagnosed stage 0 to II breast cancer priate treatment is oxaliplatin, fluorouracil, and leucovorin without symptoms suggestive of metastatic disease and (FOLFOX) (Option C). Stage III is defined by metastases to the normal comprehensive metabolic profile and alkaline local-regional lymph nodes. Stage III colon cancer is potentially phosphatase measurement should not undergo routine curable, although the risk of treatment failure increases with imaging (Option D). This patient has stage I breast cancer. the number of positive nodes. Currently, all patients with stage Consensus guidelines recommend against routine staging III disease are recommended to receive adjuvant chemotherapy scans for asymptomatic patients with early-stage (0-II) after definitive surgery, as large randomized trials have shown breast cancer given the low incidence of asymptomatic that this treatment modestly improves the likelihood of cure.

Item 3 Answer: D Item 4 Answer: C Educational Objective: Avoid unnecessary imaging in a Educational Objective: Treat stage III colon cancer. patient with stage 0 to II invasive breast cancer. This patient has stage IIIB colon cancer, and the most appro- Patients with newly diagnosed stage 0 to II breast cancer priate treatment is oxaliplatin, fluorouracil, and leucovorin without symptoms suggestive of metastatic disease and (FOLFOX) (Option C). Stage III is defined by metastases to the normal comprehensive metabolic profile and alkaline local-regional lymph nodes. Stage III colon cancer is potentially phosphatase measurement should not undergo routine curable, although the risk of treatment failure increases with imaging (Option D). This patient has stage I breast cancer. the number of positive nodes. Currently, all patients with stage Consensus guidelines recommend against routine staging III disease are recommended to receive adjuvant chemotherapy scans for asymptomatic patients with early-stage (0-II) after definitive surgery, as large randomized trials have shown breast cancer given the low incidence of asymptomatic that this treatment modestly improves the likelihood of cure. b metastases and the risk of false-positive findings on routine The combination of oxaliplatin plus a fluoropyrimidine such = as 5-fluorouracil (5-FU) or its oral prodrug, capecitabine, has wn staging studies. = The prevalence of a positive bone scan for asymp- long been the accepted standard postoperative management @ TM wn tomatic women with apparent stage I, II, and III breast for stage III colon cancer. The most commonly used regimen is mat cancer has been reported as 5%, 6%, and 14%, respectively. the FOLFOX regimen of 5-FU, leucovorin, and oxaliplatin. 5-FU = a. Chest radiography is rarely abnormal in asymptomatic is given with the reduced folate leucovorin, which is inactive (2) patients with stage I or II breast cancer and positive in 7% alone but causes 5-FU to bind more tightly to its target enzyme. here = of patients with stage III disease. Bone scans should be Oxaliplatin with oral capecitabine is also an acceptable regimen 2 < restricted to patients with either localized bone pain or for adjuvant treatment of stage III colon cancer. Oo wn elevation of alkaline phosphatase levels, and chest imaging Not all drugs that are useful for treating metastatic should be restricted to patients with pulmonary symptoms disease are active in the adjuvant setting. Irinotecan, beva- (Option A). cizumab (Option A), and cetuximab have all been shown to CT of the chest, abdomen, and pelvis (Option B) is be ineffective in improving survival in the adjuvant setting, not recommended for this patient given the small pro- yet all are part of standard treatment of metastatic disease. For portion of patients with stage I breast cancer and asymp- example, the anti-vascular endothelial growth factor mono- tomatic metastatic disease. Advanced imaging would be clonal antibody bevacizumab is often given concurrently with indicated in patients with abdominal or pelvic symp- first-line cytotoxic chemotherapy regimens in patients with toms, abnormal physical examination, or unexplained metastatic colon cancer. This agent has essentially no antitu- elevation of aminotransferase or alkaline phosphatase mor activity in colorectal cancer on its own, but it does poten- levels. Patients with stage II] breast cancer have an ele- tiate other chemotherapies, resulting in a modestly increased vated risk of asymptomatic distant metastases (14% in duration of progression-free survival, and in some studies, in one study) and are therefore recommended to undergo increased duration of overall survival. Because bevacizumab is routine imaging. CT of the chest, abdomen, and pelvis is not an effective adjuvant treatment for stage III colon cancer, most commonly used as the approach to staging. The role treatment with this agent is not appropriate. of PET/CT is not as well defined in staging patients with Capecitabine (Option B) without oxaliplatin would be breast cancer. insufficient treatment for stage III colon cancer in the absence MRI of the brain (Option C) is not recommended for of some specific contraindication to receiving oxaliplatin. patients with newly diagnosed breast cancer in the absence Unlike rectal cancer, local recurrence in colon cancer is of symptoms suggestive of central nervous system involve- rare, so radiation therapy (Option D) is not a routine part of ment (brain metastases or leptomeningeal disease). Brain colon cancer management. metastasis occurs in only a small proportion of patients with Randomized clinical trials demonstrate prolonged metastatic breast cancer and generally later in the disease disease-free survival and prolonged overall survival in course. patients who receive adjuvant chemotherapy for stage III cancer. No further therapy (Option E) would be inappro- priate in the absence of compelling co-morbidities, which e Imaging studies for staging are not recommended in would increase the risk of treatment toxicity and shorten asymptomatic patients with newly diagnosed stage 0 survival, independent of the colon cancer. to II breast cancer.

b metastases and the risk of false-positive findings on routine The combination of oxaliplatin plus a fluoropyrimidine such = as 5-fluorouracil (5-FU) or its oral prodrug, capecitabine, has wn staging studies. = The prevalence of a positive bone scan for asymp- long been the accepted standard postoperative management @ TM wn tomatic women with apparent stage I, II, and III breast for stage III colon cancer. The most commonly used regimen is mat cancer has been reported as 5%, 6%, and 14%, respectively. the FOLFOX regimen of 5-FU, leucovorin, and oxaliplatin. 5-FU = a. Chest radiography is rarely abnormal in asymptomatic is given with the reduced folate leucovorin, which is inactive (2) patients with stage I or II breast cancer and positive in 7% alone but causes 5-FU to bind more tightly to its target enzyme. here = of patients with stage III disease. Bone scans should be Oxaliplatin with oral capecitabine is also an acceptable regimen 2 < restricted to patients with either localized bone pain or for adjuvant treatment of stage III colon cancer. Oo wn elevation of alkaline phosphatase levels, and chest imaging Not all drugs that are useful for treating metastatic should be restricted to patients with pulmonary symptoms disease are active in the adjuvant setting. Irinotecan, beva- (Option A). cizumab (Option A), and cetuximab have all been shown to CT of the chest, abdomen, and pelvis (Option B) is be ineffective in improving survival in the adjuvant setting, not recommended for this patient given the small pro- yet all are part of standard treatment of metastatic disease. For portion of patients with stage I breast cancer and asymp- example, the anti-vascular endothelial growth factor mono- tomatic metastatic disease. Advanced imaging would be clonal antibody bevacizumab is often given concurrently with indicated in patients with abdominal or pelvic symp- first-line cytotoxic chemotherapy regimens in patients with toms, abnormal physical examination, or unexplained metastatic colon cancer. This agent has essentially no antitu- elevation of aminotransferase or alkaline phosphatase mor activity in colorectal cancer on its own, but it does poten- levels. Patients with stage II] breast cancer have an ele- tiate other chemotherapies, resulting in a modestly increased vated risk of asymptomatic distant metastases (14% in duration of progression-free survival, and in some studies, in one study) and are therefore recommended to undergo increased duration of overall survival. Because bevacizumab is routine imaging. CT of the chest, abdomen, and pelvis is not an effective adjuvant treatment for stage III colon cancer, most commonly used as the approach to staging. The role treatment with this agent is not appropriate. of PET/CT is not as well defined in staging patients with Capecitabine (Option B) without oxaliplatin would be breast cancer. insufficient treatment for stage III colon cancer in the absence MRI of the brain (Option C) is not recommended for of some specific contraindication to receiving oxaliplatin. patients with newly diagnosed breast cancer in the absence Unlike rectal cancer, local recurrence in colon cancer is of symptoms suggestive of central nervous system involve- rare, so radiation therapy (Option D) is not a routine part of ment (brain metastases or leptomeningeal disease). Brain colon cancer management. metastasis occurs in only a small proportion of patients with Randomized clinical trials demonstrate prolonged metastatic breast cancer and generally later in the disease disease-free survival and prolonged overall survival in course. patients who receive adjuvant chemotherapy for stage III cancer. No further therapy (Option E) would be inappro- priate in the absence of compelling co-morbidities, which e Imaging studies for staging are not recommended in would increase the risk of treatment toxicity and shorten asymptomatic patients with newly diagnosed stage 0 survival, independent of the colon cancer. to II breast cancer. e Brain metastasis occurs in only a small proportion of patients with metastatic breast cancer and generally e The FOLFOX regimen of 5-fluorouracil, leucovorin, and later in the disease course. oxaliplatin or oxaliplatin with oral capecitabine is the most appropriate adjuvant therapy for stage IIT colon cancer. Bibliography Bychkovsky BL, Guo H, Sutton J, et al. Use and yield of baseline imaging and ¢ Unlike rectal cancer, adjuvant irradiation is not part of laboratory testing in stage II breast cancer. Oncologist. 2016;21:1495-1501. the routine management of colon cancer. [PMID: 27551013]

e Brain metastasis occurs in only a small proportion of patients with metastatic breast cancer and generally e The FOLFOX regimen of 5-fluorouracil, leucovorin, and later in the disease course. oxaliplatin or oxaliplatin with oral capecitabine is the most appropriate adjuvant therapy for stage IIT colon cancer. Bibliography Bychkovsky BL, Guo H, Sutton J, et al. Use and yield of baseline imaging and ¢ Unlike rectal cancer, adjuvant irradiation is not part of laboratory testing in stage II breast cancer. Oncologist. 2016;21:1495-1501. the routine management of colon cancer. [PMID: 27551013] 68