20 Prostate, Bladder, and Kidney Cancer

Russell K. Pachynski

QUESTIONS

Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer that is BEST in each case unless instructed otherwise.

Question 20.1 Activating mutations in which of the following genes is seen in patients with hereditary papillary renal cell carcinoma?

A. VHL

B. MET

C. FLCN

D. SDHB

Question 20.2 A 56-year-old moderately obese woman with a medical history of chronic hypertension well controlled on a thiazide diuretic presents to the emergency department with a 1-day history of abdominal pain, diarrhea, nausea, and fever. General physical examination is significant only for some mild abdominal tenderness; negative stool guaiac; a white blood cell count of 14.2/μL; hemoglobin of 14.5 g/dL; a normal platelet count; normal electrolytes, amylase, lipase, and transaminases; and a creatinine of 0.9 mg/dL. Workup includes an abdominal computed tomography (CT) scan, which is remarkable for a 1.5-cm enhancing left renal mass in the left lower pole that is interpreted by the radiologist as a “probable renal cell carcinoma” without evidence of other metastases. The patient undergoes a laparoscopic partial nephrectomy. There are no postoperative complications, and she is back to work 3 weeks later. Postoperative creatinine is 1.3 and pathology reveals a 2.5-cm renal cell carcinoma, granular cell type, that is confined to the renal parenchyma. No lymph nodes were recovered. The next appropriate step is:

A. Open retroperitoneal lymph node dissection.

B. Adjuvant sunitinib.

C. Adjuvant local radiotherapy.

D. Submission of pathology specimen for second review.

Question 20.3 A 55-year-old woman undergoes partial nephrectomy for clear cell carcinoma of the kidney, Fuhrman grade IV. The patient does well for 10 years, at which time she develops a pathologic intratrochanteric fracture of her left hip. CT scanning of the chest, abdomen, pelvis, and brain and bone scan reveals no other sites of disease. The most appropriate next step is:

A. Radiation alone.

B. High-dose interleukin-2 alone.

C. Orthopedic resection of the tumor with reconstruction followed by radiation.

D. Temsirolimus.

Questions 20.4–5 A 76-year-old man with chronic obstructive pulmonary disorder and diabetes mellitus presents with back pain and confusion. Workup reveals extensive metastatic disease in the lungs, bones, and liver and a 6-cm tumor in the kidney. There is no evidence of cord compression. Laboratory studies reveal a calcium level of 11.5 mg/dL, lactate dehydrogenase (LDH) of 600, and a creatinine level of 2.0 mg/dL. After hydration and zoledronate, his calcium normalizes, hemoglobin is 9.5, creatinine decreases to 1.7, and Eastern Cooperative Oncology Group performance status is 2.

Question 20.4 Based on MSKCC risk factors, this patient would be considered:

A. No risk.

B. Low risk.

C. Intermediate risk.

D. Poor risk.

Question 20.5 The most appropriate therapy in this case is:

A. Interferon-α.

B. Temsirolimus.

C. Sunitinib.

D. Sorafenib.

Question 20.6 A 25-year-old Caucasian man without a medical history presents with hematuria. Workup reveals bilateral renal cysts, at least one of them suspicious for malignancy. Family history is significant for a pheochromocytoma in his father and a pancreatic islet cell tumor and early death from kidney cancer in a paternal aunt. The most likely familial cancer syndrome is:

A. Von Hippel–Lindau disease.

B. Birt–Hogg–Dubé syndrome.

C. Hereditary papillary renal cancer.

D. Hereditary leiomyomatosis and renal cancer.

Question 20.7 Which of the following associated with loss of VHL function is most likely to lead to tumor angiogenesis?

A. Modulation of NF-kB activity and downregulation of JUNB

B. Increase in matrix metalloproteinases

C. Increase in hypoxia inducible factor (HIF)

D. Destabilization of microtubule formation

Question 20.8 Inactivation or alteration in which of the following tumor suppressor genes is implicated in the pathogenesis of invasive bladder cancer?

A. TP53

B. RB1

C. PTEN

D. All of the above

Question 20.9 A patient with hematuria is taken to the operating room, where an examination under general anesthesia reveals a mobile bladder. Resection of the papillary lesion reveals grade III urothelial papillary carcinoma, and multiple biopsies of the erythematous areas of the bladder all reveal diffuse carcinoma in situ. Muscle is present in the pathologic specimens, and there is no evidence for invasive tumor. The appropriate therapy is:

A. Intravesical Bacillus Calmette–Guérin (BCG) vaccine.

B. Intravesical cyclophosphamide.

C. Radiation.

D. Cystectomy.

Question 20.10 The patient receives definitive treatment, as well as with a follow-up maintenance program; however, 4 months after initiating the maintenance BCG program, the urologist notes multiple recurrent papillary lesions. Repeat biopsy reveals urothelial cancer invasive into muscle. CT scans of the chest, abdomen, and pelvis are unremarkable, creatinine remains normal at 1.2 mg/dL, and his performance status is excellent. Appropriate initial therapy at this point is:

A. Reinduction with intravesical BCG.

B. Intravesical chemotherapy with mitomycin-C.

C. Partial cystectomy.

D. Cisplatin-based multiagent chemotherapy.

Question 20.11 Which of the following is the most common molecular abnormality seen in patients with prostate cancer?

A. KRAS mutation

B. BRAF mutation

C. p53 mutation

D. Chromosomal translocations involving TMPRSS2

Question 20.12 Which of the following are risk factors for cancer of the male urethra?

A. HPV-16

B. Chronic irritation

C. Infection

D. Caucasian race

Questions 20.13–14 A 62-year-old woman is newly diagnosed with muscle-invasive bladder cancer. She quit smoking 10 years ago, had a non–ST-elevated myocardial infarction 4 years ago, underwent coronary artery bypass surgery and has had no residual cardiac symptoms, takes only a beta-blocker and a thiazide for hypertension, and has normal laboratory test results, including a creatinine of 0.9. Cystoscopic biopsy revealed a muscle-invasive bladder cancer without associated carcinoma in situ (Tcis), and CT of the chest, abdomen, and pelvis is unremarkable.

Question 20.13 Which of the following statements about radical cystectomy is most CORRECT?

A. An orthotopic neobladder is less effective in women than in men.

B. An abdominal wall diversion will require a urostomy bag.

C. An orthotopic neobladder will require the patient to be willing and able to perform self-catheterization.

D. Metabolic acidosis is not a significant problem with continent diversions.

Question 20.14 Which of the following statements about combined radiation and chemotherapy is most CORRECT?

A. Toxicity profile and tolerability of combined radiation and chemotherapy are significantly better than that of radical cystectomy.

B. Long-term cancer outcome is similar to cystectomy.

C. It is preferred over cystectomy because of her cardiac history.

D. It will obviate the need for cystectomy.

Question 20.15 Which of the following is CORRECT about neoadjuvant chemotherapy?

A. Three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin before cystectomy are a standard of care.

B. Gemcitabine/carboplatin should be considered to decrease the risk of renal failure with cystectomy.

C. It increases the risk of surgical complications of cystectomy.

D. It should always be used with an organ preservation approach but is optional if cystectomy is chosen.

Question 20.16 Which of the following genes is most commonly found to be abnormally altered in invasive (≥T2) urothelial carcinoma of the bladder?

A. ERBB2

B. TP53

C. MDM2

D. FGFR3

Question 20.17 A 71-year-old man without significant medical history presents with hematuria and flank pain. CT scan reveals a mass at the pelvic–ureteral junction with associated hydronephrosis, but no associated lymphadenopathy. Cystoscopy and ureteroscopy reveal an obstructing mass at the pelvic–ureteral junction, and cytology is diagnostic for urothelial cancer. Which of the following is the most appropriate therapy?

A. Open nephroureterectomy and bladder cuff resection

B. Open radical nephrectomy with retroperitoneal lymph node dissection

C. Laparoscopic radical nephrectomy without retroperitoneal lymph node dissection

D. Definitive radiation and combined chemotherapy

Question 20.18 A 51-year-old man with a strong family history of prostate cancer, a normal digital rectal examination, no significant comorbid medical problems, and a PSA of 2.9 seeks advice on prostate cancer prevention. He is sexually active in a monogamous relationship and denies any urinary or rectal symptoms. Which is the most likely to reduce his risk of developing prostate cancer?

A. Reducing his alcohol intake.

B. Taking supplemental high dose vitamin E.

C. Avoiding high fat intake, reducing his BMI (avoiding obesity), and increasing his physical activity.

D. Increasing his calcium/vitamin D intake.

Questions 20.19–20 A 71-year-old white man with a history of hypertension, hyperlipidemia, coronary artery disease, and prior angioplasty with stent placement, but no prior myocardial infarction, is noted to have an increase in his PSA from 3.0 to 3.9 ng/mL and then to 4.6 ng/mL over 19 months. He is a semiretired accountant, swims actively three times per week, and helps care for his mildly demented 95-year-old father. General physical examination is unremarkable; a rectal examination reveals a mildly enlarged prostate gland without any palpable nodules.

Question 20.19 The most CORRECT statement about this case is:

A. Biopsy should be discussed because the PSA increase is >0.75 ng/ mL/year.

B. Biopsy should not be discussed because PSA is normal for his age.

C. Biopsy should not be discussed because his expected survival makes treatment not worthwhile, even if prostate cancer is discovered.

D. Biopsy should be discussed because the PSA is >4 ng/mL.

E. The free-to-total PSA ratio will determine the need for biopsy.

Question 20.20 Biopsy reveals Gleason 8 prostate cancer in six of six cores. CT scan of the abdomen and pelvis and bone scan are unremarkable. The most appropriate therapy is:

A. Radical retropubic prostatectomy.

B. Three-dimensional conformal radiotherapy with concomitant androgen ablation.

C. Interstitial radiotherapy with 125I.

D. All of the above.

Question 20.21 After discussion with a radiation oncologist and a urologist, the patient elects to undergo combined androgen ablation and external beam radiation therapy. The androgen ablation is administered before the radiation therapy and continued for 3 months thereafter. Radiotherapy is complicated only by a mild diarrhea that resolves once the radiation therapy is complete. The PSA nadirs at 1.2 ng/mL; however, 9 months after his last dose of the luteinizing hormone–releasing hormone (LHRH) agonist, the PSA increases to 2.4 ng/mL and then to 3.6 ng/mL 1 month later. Testosterone level is normal at 350 ng/mL. The most appropriate next therapeutic and/or diagnostic maneuver is:

A. Perform MRI of the pelvis to assess for local recurrence.

B. Reinitiate androgen ablation.

C. Refer the patient to a urologist for salvage prostatectomy.

D. Initiate docetaxel-based chemotherapy.

Question 20.22 The patient is treated with an LHRH agonist along with the antiandrogen bicalutamide. PSA declines to 0.8 ng/mL, but after 10 months, the PSA begins to slowly increase to a value of 3.7. He continues to feel well and has minimal urinary symptoms, no bone pain, and no weight loss. The most appropriate therapy at this point is:

A. Docetaxel-based chemotherapy.

B. Discontinuing the antiandrogen bicalutamide.

C. Hospice care.

D. Radionuclide therapy with strontium-98 (Metastron).

Question 20.23 Infestation with which of the following parasites is a risk factor for developing bladder cancer?

A. Clonorchis sinensis

B. Opisthorchis viverrini

C. Schistosoma haematobium

D. None of the above

Question 24–25 A 51-year-old black male executive with no medical history undergoes a routine PSA screening evaluation and is found to have a PSA of 5.5 ng/mL. Biopsy reveals a Gleason 3 + 3 prostate cancer in two of six biopsy cores. After discussion with a radiation oncologist and urologist, he elects to receive treatment with a radical retropubic prostatectomy.

Question 20.24 Which of the following statements about the surgery is TRUE?

A. Robotic laparoscopic prostatectomy is associated with a lower incidence of impotence than open retropubic prostatectomy.

B. The incidence of impotence under the assumption that a bilateral nerve sparing procedure can be performed is <10%.

C. Problems with incontinence persist in approximately 20% of patients.

D. Surgical experience has only a minimal impact on the positive margin rate.

Question 20.25 Surgical pathology confirms a Gleason score 6 tumor in both lobes of the prostate. There is a focal surgical positive margin. There is no evidence of seminal vesicle or lymph node invasion. His postoperative PSA is undetectable, and he has good continence. The most appropriate next step is:

A. Adjuvant radiotherapy.

B. Repeat surgical exploration with possible reexcision of the prostatic bed.

C. Pelvic CT scan.

D. Prostascint scan.

Question 20.26 The patient maintains an undetectable PSA until 8 years later (at the age of 59 years), recurrent biochemical disease is noted. After appropriate discussion, androgen ablation with an LHRH agonist alone is initiated, and the PSA once again becomes undetectable. The patient maintains an undetectable PSA while on androgen ablation for 3 years, when he develops sudden midback pain after lifting his grandson. There are no associated neurologic signs or symptoms. Bone scan shows marked uptake at the T8 vertebra and PSA remains undetectable. The most appropriate therapeutic or diagnostic maneuver is:

A. Immediate radiotherapy to T8.

B. Therapy with ketoconazole, 400 mg three times daily with hydrocortisone replacement.

C. Spinal MRI to rule out cord compression.

D. Bone densitometry to assess for osteoporosis.

Question 20.27 A 75-year-old man with diabetes, hypertension, and coronary artery disease who is receiving atorvastatin, glyburide, and an angiotensin-converting enzyme inhibitor is under surveillance after external beam radiotherapy for a Gleason 3 + 3 prostate cancer that was diagnosed and treated 10 years earlier when he was found to have a PSA of 4.3 on routine screening. His PSA level, which had been 0.2 ng/mL, has increased to 0.3, 0.35, and then 0.40 over the period of 18 months. The most appropriate therapy at this time is:

A. Androgen ablation with an LHRH agonist.

B. Continued active surveillance.

C. High-intensity focused ultrasound to his prostate.

D. High-dose (150 mg) bicalutamide.

Question 20.28 A 65-year-old man has been receiving combined androgen ablation with leuprolide and bicalutamide for 4 years for biochemical recurrence after radical prostatectomy. His PSA has increased from an undetectable nadir to 1.1 ng/mL on serial measurement over the period of 6 months. The PSA then continues to increase 2 months later to 2.5, with serum testosterone of 10 ng/mL. Bone scan and CT of the abdomen/pelvis do not reveal any metastatic disease, and he remains asymptomatic. The most appropriate therapy option is:

A. Continue current treatment regimen and active surveillance.

B. Docetaxel-based chemotherapy.

C. Start enzalutamide.

D. Discontinue bicalutamide.

Question 20.29 Which of the following has the highest risk of developing prostate cancer?

A. A 60-year-old Caucasian male with no family history of cancer.

B. A 60-year-old African-American male with a father with prostate cancer.

C. A 40-year-old Asian male.

D. A 40-year-old obese Caucasian male.

Question 20.30 Genetic alterations in which of the following is most common in prostate adenocarcinoma?

A. NRIP1

B. FOXA1

C. PTEN

D. CDK2

Question 20.31 Which of the following statements about the androgen receptor is most CORRECT?

A. The majority of its activity in prostate cancer is due to its cytoplasmic effects.

B. Upregulation of androgen receptor expression has been linked to prostate cancer development.

C. Castration leads to complete inactivation of all androgen receptor-mediated pathways.

D. Castrate-resistant prostate cancer (CRPC) is associated with upregulation of androgen receptor expression.

Question 20.32 A 63-year-old uncircumcised man without any significant medical history presents to his physician with an inability to retract the foreskin. Examination reveals phimosis, with an underlying painless ulcerated mass of 1 × 2 cm. A 2.5-cm hard node is palpated in the left inguinal region. Biopsy of the penile lesion reveals squamous cell cancer. In addition to wide surgical resection of the primary lesion, other appropriate therapeutic and/or diagnostic maneuvers at this time include:

A. Four-week course of a broad-spectrum antibiotic.

B. Left inguinal lymph node dissection.

C. Bilateral inguinal radiotherapy.

D. Taxane-based chemotherapy.

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