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Genitourinary Cancer of a testicular mass is contraindicated because of concern Men treated with chemotherapy for testicular cancer are regarding tumor seeding to the scrotum and inguinal nodes. at risk for many different long-term complications, including When the diagnosis is confirmed, evaluation with chest radiog- cardiovascular disease, metabolic syndrome, pulmonary tox- raphy, CT of the abdomen and pelvis, and tumor marker levels icity, hypogonadism, infertility, chronic kidney disease, and after orchiectomy are used for staging. Marker levels fall at pre- neurotoxicity. The risk of a second solid tumor is approxi- dictable rates after surgery, and sufficient time is needed before mately twofold higher than in men without a history of tes- concluding that markers remain elevated after orchiectomy. ticular cancer. Histologically, testicular cancers are either pure semino- mas or nonseminomatous germ cell tumors. Tumors with e Measurement of o-fetoprotein and B-human chorionic seminoma pathology but elevated o-fetoprotein levels are gonadotropin is important before and after inguinal termed mixed germ cell tumors and are managed as a non- orchiectomy for staging and prognosis of testicular seminomatous germ cell tumor. Management depends on cancer. histology, the results of staging studies, and the presence or absence of serum tumor marker elevation after orchiectomy. It e Patients with stage II seminoma can be treated with is essential to discuss and offer sperm cryopreservation before adjuvant irradiation or cisplatin-based chemotherapy, although chemotherapy is preferred with more exten- initiating additional treatment. sive lymph node involvement. For pure seminoma, active surveillance can be offered after surgery for early-stage disease; adjuvant irradiation or che- e Patients with seminoma and residual masses that show

is essential to discuss and offer sperm cryopreservation before adjuvant irradiation or cisplatin-based chemotherapy, although chemotherapy is preferred with more exten- initiating additional treatment. sive lymph node involvement. For pure seminoma, active surveillance can be offered after surgery for early-stage disease; adjuvant irradiation or che- e Patients with seminoma and residual masses that show motherapy with one to two cycles of carboplatin are also appro- negative results on PET scan can be followed, with priate options. Stage II seminoma is defined by retroperitoneal resection based on any further increase in size; masses lymph node metastases. These patients can be treated with that show positive results on PET scan should be either irradiation to the paraaortic lymph nodes and superior resected.

priate options. Stage II seminoma is defined by retroperitoneal resection based on any further increase in size; masses lymph node metastases. These patients can be treated with that show positive results on PET scan should be either irradiation to the paraaortic lymph nodes and superior resected. ipsilateral pelvis or chemotherapy, depending on the extent of e Patients with nonseminoma and clinically metastatic lymph node involvement. Patients with more extensive lymph nodes can be treated with retroperitoneal lymph node node involvement should receive chemotherapy. For higher- dissection or chemotherapy; chemotherapy is preferred stage disease, cisplatin-based chemotherapy is used. PET/CT if there are several positive nodes, large nodes (>5 cm), can be used to determine whether residual masses after che- or elevated serum tumor markers. motherapy require resection. Residual masses that show nega- tive results on PET scan may be benign and can be followed, with resection based on any further increase in size. Residual Renal Cell Carcinoma masses that show positive results on PET scan should be Renal cancers typically arise in the cortex of the kidney. The promptly resected, as cure remains possible. most common histology is clear cell carcinoma, which is also After resection, patients with early-stage nonseminoma- the most responsive to medical treatment. In the past, the most tous germ cell tumors can be managed with active surveillance common presenting symptoms of renal cell carcinoma were (in selected patients), retroperitoneal lymph node dissection hematuria, abdominal mass, and weight loss, but most (RPLND), or limited chemotherapy. Adjuvant chemotherapy is patients are currently diagnosed incidentally based on imag- recommended in patients with nodal involvement on RPLND. ing studies done for other reasons. Ultrasonography can be Persistence of tumor marker elevation after orchiectomy with- used to differentiate benign cysts from complex cysts or solid out abnormal imaging findings is also an indication for chemo- masses. If a lesion is not clearly a benign cyst, CT is indicated therapy. Some patients with clinically metastatic retroperitoneal for further evaluation. Patients with CT findings pathogno- nodes can be managed with RPLND or primary chemotherapy monic for renal cell cancer do not need a confirmatory renal if markers are negative and nodal metastases are limited and biopsy to establish the diagnosis. small. For patients with several positive nodes, large nodes Many different paraneoplastic syndromes can be seen in (>5 cm), or elevated markers, chemotherapy is recommended. patients with renal cell carcinoma, including anemia, hepatic Any residual masses after chemotherapy should be resected. dysfunction in the absence of liver metastases (known as For the first year after treatment, patients should be clini- Stauffer syndrome), fever, hypercalcemia, erythrocytosis, AA cally evaluated every 2 to 3 months and should have tumor amyloidosis, thrombocytosis, and polymyalgia rheumatica. marker measurement and imaging studies periodically, with spe- Many of these conditions can improve with resection of the cific intervals determined by histology, stage, and previous treat- primary tumor, metastatic sites, or both. ment. After the first year, evaluations can be performed less often. A suspicious solitary renal mass less than 4 cm does not Patients with recurrent disease are treated and may necessarily require treatment. Active surveillance is an option well be cured with combination chemotherapy or high-dose for such lesions. Treatment can be either with surgery or abla- chemotherapy and autologous hematopoietic stem cell tion, most commonly cryoablation. Larger lesions require sur- transplantation. gical treatment. This consists of either radical nephrectomy or

ipsilateral pelvis or chemotherapy, depending on the extent of e Patients with nonseminoma and clinically metastatic lymph node involvement. Patients with more extensive lymph nodes can be treated with retroperitoneal lymph node node involvement should receive chemotherapy. For higher- dissection or chemotherapy; chemotherapy is preferred stage disease, cisplatin-based chemotherapy is used. PET/CT if there are several positive nodes, large nodes (>5 cm), can be used to determine whether residual masses after che- or elevated serum tumor markers. motherapy require resection. Residual masses that show nega- tive results on PET scan may be benign and can be followed, with resection based on any further increase in size. Residual Renal Cell Carcinoma masses that show positive results on PET scan should be Renal cancers typically arise in the cortex of the kidney. The promptly resected, as cure remains possible. most common histology is clear cell carcinoma, which is also After resection, patients with early-stage nonseminoma- the most responsive to medical treatment. In the past, the most tous germ cell tumors can be managed with active surveillance common presenting symptoms of renal cell carcinoma were (in selected patients), retroperitoneal lymph node dissection hematuria, abdominal mass, and weight loss, but most (RPLND), or limited chemotherapy. Adjuvant chemotherapy is patients are currently diagnosed incidentally based on imag- recommended in patients with nodal involvement on RPLND. ing studies done for other reasons. Ultrasonography can be Persistence of tumor marker elevation after orchiectomy with- used to differentiate benign cysts from complex cysts or solid out abnormal imaging findings is also an indication for chemo- masses. If a lesion is not clearly a benign cyst, CT is indicated therapy. Some patients with clinically metastatic retroperitoneal for further evaluation. Patients with CT findings pathogno- nodes can be managed with RPLND or primary chemotherapy monic for renal cell cancer do not need a confirmatory renal if markers are negative and nodal metastases are limited and biopsy to establish the diagnosis. small. For patients with several positive nodes, large nodes Many different paraneoplastic syndromes can be seen in (>5 cm), or elevated markers, chemotherapy is recommended. patients with renal cell carcinoma, including anemia, hepatic Any residual masses after chemotherapy should be resected. dysfunction in the absence of liver metastases (known as For the first year after treatment, patients should be clini- Stauffer syndrome), fever, hypercalcemia, erythrocytosis, AA cally evaluated every 2 to 3 months and should have tumor amyloidosis, thrombocytosis, and polymyalgia rheumatica. marker measurement and imaging studies periodically, with spe- Many of these conditions can improve with resection of the cific intervals determined by histology, stage, and previous treat- primary tumor, metastatic sites, or both. ment. After the first year, evaluations can be performed less often. A suspicious solitary renal mass less than 4 cm does not Patients with recurrent disease are treated and may necessarily require treatment. Active surveillance is an option well be cured with combination chemotherapy or high-dose for such lesions. Treatment can be either with surgery or abla- chemotherapy and autologous hematopoietic stem cell tion, most commonly cryoablation. Larger lesions require sur- transplantation. gical treatment. This consists of either radical nephrectomy or 30

Lymphoid Malignancies partial nephrectomy, depending on the size and location of the tumor (TURBT) and examination under anesthesia is per- primary tumor. At the present time, adjuvant therapy is not formed to determine histology and depth of invasion. recommended. Although sunitinib has been approved by the Most patients are found to have non-muscle invasive dis- FDA as an adjuvant therapy following surgery, its effect on ease. This can include exophytic lesions (Ta, which can be low survival has not been consistently proven and it is associated grade or high grade), carcinoma in situ (Tis, always high with significant toxicity. Postoperative surveillance to identify grade), or early-stage invasive cancer (T1). Small low-grade Ta recurrent disease is indicated, with the frequency of interven- tumors are treated with TURBT followed by observation or tions depending on the extent of local disease. This typically intravesical chemotherapy. All other noninvasive disease is consists of a history and physical examination, basic labora- treated with TURBT followed by either intravesical bacillus tory studies, and imaging of the chest and abdomen. Calmette-Guérin or intravesical chemotherapy. After primary Resection or debulking of the primary renal cell cancer treatment, cystoscopic surveillance is indicated because of the improves survival for select patients with metastatic disease. risk for recurrent disease. There is a higher risk for muscle Surgery or other local therapies (such as stereotactic radiation invasive recurrence for patients with larger tumors, less dif- therapy) also have a role in the treatment of isolated or several ferentiated tumors, tumors that invade into the lamina pro- easily resected areas of metastatic disease. pria, and tumors with multifocal or noninvasive recurrence. No specific front-line therapy has been shown superior Most patients require cystoscopy 3 months after initial therapy, for patients who present with metastatic clear cell or non- with subsequent cystoscopy at periodic intervals based on risk clear cell histology. Various agents, including immune check- of recurrence. Cystectomy can be considered for patients at point inhibitors and tyrosine kinase inhibitors, have been high risk for developing muscle-invasive disease. shown to be effective. Combination therapy with axitinib, a If muscle-invasive disease is diagnosed, imaging studies vascular endothelial growth factor inhibitor, and the immune are indicated for staging. Cystectomy is indicated, with or checkpoint inhibitor pembrolizumab has been shown as without neoadjuvant cisplatin-based chemotherapy. Partial effective in the front-line setting. cystectomy can be considered in very carefully selected patients. For patients unable or unwilling to undergo cystec- tomy, maximal TURBT can be combined with concurrent HVC e Patients with CT findings pathognomonic for renal cell chemoradiotherapy for those with limited disease. Adjuvant carcinoma do not need a biopsy to confirm the diagnosis. chemotherapy after surgical resection is appropriate to con- e Many different paraneoplastic syndromes can be seen sider in patients with high-risk features, such as positive nodes in patients with renal cell carcinoma, including anemia, and extension beyond the bladder. hepatic dysfunction in the absence of liver metastases, Treatment of metastatic disease requires systemic therapy, fever, hypercalcemia, erythrocytosis, AA amyloidosis, and treatment outcomes remain poor. Cisplatin-based combi- thrombocytosis, and polymyalgia rheumatica. nation chemotherapy remains the evidence-based choice,

partial nephrectomy, depending on the size and location of the tumor (TURBT) and examination under anesthesia is per- primary tumor. At the present time, adjuvant therapy is not formed to determine histology and depth of invasion. recommended. Although sunitinib has been approved by the Most patients are found to have non-muscle invasive dis- FDA as an adjuvant therapy following surgery, its effect on ease. This can include exophytic lesions (Ta, which can be low survival has not been consistently proven and it is associated grade or high grade), carcinoma in situ (Tis, always high with significant toxicity. Postoperative surveillance to identify grade), or early-stage invasive cancer (T1). Small low-grade Ta recurrent disease is indicated, with the frequency of interven- tumors are treated with TURBT followed by observation or tions depending on the extent of local disease. This typically intravesical chemotherapy. All other noninvasive disease is consists of a history and physical examination, basic labora- treated with TURBT followed by either intravesical bacillus tory studies, and imaging of the chest and abdomen. Calmette-Guérin or intravesical chemotherapy. After primary Resection or debulking of the primary renal cell cancer treatment, cystoscopic surveillance is indicated because of the improves survival for select patients with metastatic disease. risk for recurrent disease. There is a higher risk for muscle Surgery or other local therapies (such as stereotactic radiation invasive recurrence for patients with larger tumors, less dif- therapy) also have a role in the treatment of isolated or several ferentiated tumors, tumors that invade into the lamina pro- easily resected areas of metastatic disease. pria, and tumors with multifocal or noninvasive recurrence. No specific front-line therapy has been shown superior Most patients require cystoscopy 3 months after initial therapy, for patients who present with metastatic clear cell or non- with subsequent cystoscopy at periodic intervals based on risk clear cell histology. Various agents, including immune check- of recurrence. Cystectomy can be considered for patients at point inhibitors and tyrosine kinase inhibitors, have been high risk for developing muscle-invasive disease. shown to be effective. Combination therapy with axitinib, a If muscle-invasive disease is diagnosed, imaging studies vascular endothelial growth factor inhibitor, and the immune are indicated for staging. Cystectomy is indicated, with or checkpoint inhibitor pembrolizumab has been shown as without neoadjuvant cisplatin-based chemotherapy. Partial effective in the front-line setting. cystectomy can be considered in very carefully selected patients. For patients unable or unwilling to undergo cystec- tomy, maximal TURBT can be combined with concurrent HVC e Patients with CT findings pathognomonic for renal cell chemoradiotherapy for those with limited disease. Adjuvant carcinoma do not need a biopsy to confirm the diagnosis. chemotherapy after surgical resection is appropriate to con- e Many different paraneoplastic syndromes can be seen sider in patients with high-risk features, such as positive nodes in patients with renal cell carcinoma, including anemia, and extension beyond the bladder. hepatic dysfunction in the absence of liver metastases, Treatment of metastatic disease requires systemic therapy, fever, hypercalcemia, erythrocytosis, AA amyloidosis, and treatment outcomes remain poor. Cisplatin-based combi- thrombocytosis, and polymyalgia rheumatica. nation chemotherapy remains the evidence-based choice, e Resecting or debulking a primary renal cell cancer may although immune checkpoint treatment can be given to patients

partial nephrectomy, depending on the size and location of the tumor (TURBT) and examination under anesthesia is per- primary tumor. At the present time, adjuvant therapy is not formed to determine histology and depth of invasion. recommended. Although sunitinib has been approved by the Most patients are found to have non-muscle invasive dis- FDA as an adjuvant therapy following surgery, its effect on ease. This can include exophytic lesions (Ta, which can be low survival has not been consistently proven and it is associated grade or high grade), carcinoma in situ (Tis, always high with significant toxicity. Postoperative surveillance to identify grade), or early-stage invasive cancer (T1). Small low-grade Ta recurrent disease is indicated, with the frequency of interven- tumors are treated with TURBT followed by observation or tions depending on the extent of local disease. This typically intravesical chemotherapy. All other noninvasive disease is consists of a history and physical examination, basic labora- treated with TURBT followed by either intravesical bacillus tory studies, and imaging of the chest and abdomen. Calmette-Guérin or intravesical chemotherapy. After primary Resection or debulking of the primary renal cell cancer treatment, cystoscopic surveillance is indicated because of the improves survival for select patients with metastatic disease. risk for recurrent disease. There is a higher risk for muscle Surgery or other local therapies (such as stereotactic radiation invasive recurrence for patients with larger tumors, less dif- therapy) also have a role in the treatment of isolated or several ferentiated tumors, tumors that invade into the lamina pro- easily resected areas of metastatic disease. pria, and tumors with multifocal or noninvasive recurrence. No specific front-line therapy has been shown superior Most patients require cystoscopy 3 months after initial therapy, for patients who present with metastatic clear cell or non- with subsequent cystoscopy at periodic intervals based on risk clear cell histology. Various agents, including immune check- of recurrence. Cystectomy can be considered for patients at point inhibitors and tyrosine kinase inhibitors, have been high risk for developing muscle-invasive disease. shown to be effective. Combination therapy with axitinib, a If muscle-invasive disease is diagnosed, imaging studies vascular endothelial growth factor inhibitor, and the immune are indicated for staging. Cystectomy is indicated, with or checkpoint inhibitor pembrolizumab has been shown as without neoadjuvant cisplatin-based chemotherapy. Partial effective in the front-line setting. cystectomy can be considered in very carefully selected patients. For patients unable or unwilling to undergo cystec- tomy, maximal TURBT can be combined with concurrent HVC e Patients with CT findings pathognomonic for renal cell chemoradiotherapy for those with limited disease. Adjuvant carcinoma do not need a biopsy to confirm the diagnosis. chemotherapy after surgical resection is appropriate to con- e Many different paraneoplastic syndromes can be seen sider in patients with high-risk features, such as positive nodes in patients with renal cell carcinoma, including anemia, and extension beyond the bladder. hepatic dysfunction in the absence of liver metastases, Treatment of metastatic disease requires systemic therapy, fever, hypercalcemia, erythrocytosis, AA amyloidosis, and treatment outcomes remain poor. Cisplatin-based combi- thrombocytosis, and polymyalgia rheumatica. nation chemotherapy remains the evidence-based choice, e Resecting or debulking a primary renal cell cancer may although immune checkpoint treatment can be given to patients improve survival in select patients with metastatic disease. with programmed death ligand 1—positive cancers. After further progression, single-agent therapy with either chemotherapy or an immune checkpoint inhibitor is recommended.

improve survival in select patients with metastatic disease. with programmed death ligand 1—positive cancers. After further progression, single-agent therapy with either chemotherapy or an immune checkpoint inhibitor is recommended. Bladder Cancer Bladder cancer is the most common cancer of the genitouri- e Any patient with gross hematuria should be referred for nary tract. Most patients have transitional cell carcinoma, urologic evaluation, as should any patient confirmed to which is the focus of this section. Common presenting symp- have microscopic hematuria in the absence of an appar- toms include hematuria and irritative urinary symptoms. ent benign cause; use of anticoagulants does not alter It is important to assess for gross hematuria in review of these recommendations. systems questioning for all patients and confirm with a uri- ¢ Superficial bladder cancer does not invade the muscle, nalysis ifa patient does note hematuria. Any patient with gross and treatment includes transurethral resection of the hematuria should be referred for urologic evaluation, as should bladder tumor plus intravesical chemotherapy, usually any patient confirmed to have persistent microscopic hematu- bacillus Calmette-Guérin. ria after evaluating benign causes, such as urinary tract infec- tion, nephrolithiasis, or underlying kidney disease with a glomerular source of erythrocytes. Notably, use of anticoagu- lants does not alter these recommendations. Lymphoid Malignancies The primary modality of initial evaluation is cystoscopy, with biopsy of any visible tumor or mucosal abnormality. Epidemiology and Risk Factors Random biopsy is performed if no abnormality is seen. If can- Approximately 80,000 new cases of lymphoma were diag- cer is confirmed, then transurethral resection of the bladder nosed in 2019 in the United States. The lifetime risk of 31