Genitourinary Malignancies
Praful Ravi, MB, BChir, MRCP
Wenxin (Vincent) Xu, MD
Charlene Mantia, MD
Bradley McGregor, MD
Andrew L. Schmidt, MD
A 61-year-old male is diagnosed with prostate cancer after his primary care physician found his PSA to be 12. His biopsy showed 3 cores of Gleason 4 + 3 prostate adenocarcinoma. His bone scan and MRI of his pelvis show one enlarged pelvic lymph node without any other evidence of disease.
What is his stage?
View Answer
Stage IVA
In prostate cancer, evidence of any lymph node involvement, even regional lymph nodes, is classified as stage IV disease. Some stage IV patients are still candidates for definitive therapy.
Patients with early-stage, low-risk, clinically localized prostate cancer may be candidates for definitive therapy with radical proctectomy or RT if they are clinically fit with an expected natural survival >10 years.
Suggested Readings:
National Comprehensive Cancer Network. Prostate Cancer (Version 1.2020). Accessed May 20, 2020. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 66-year-old male was treated with external beam radiotherapy plus androgen deprivation therapy for a Gleason 4 + 3 prostate cancer. His PSA nadir was 0.3. Twelve months after treatment, his PSA is 0.6.
What is the next step?
View Answer
Repeat PSA in 3 to 6 months.
The definition of biochemical recurrence after radiation therapy is an increase in PSA of 2 ng/mL above nadir. There can be a transient PSA rise (“PSA bounce”) seen about 12 to 18 months after treatment with radiation.
Suggested Readings:
Roach M III, Hanks G, Thames H Jr, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. 2006;65(4):965.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
For which one of the following men is active surveillance NOT an appropriate option?
A. A 65-year-old male with 2 cores <50% positive for Gleason 3 + 4, T2a, prostate cancer and PSA of 9
B. A 51-year-old male with 1 core <50% positive for Gleason 3 + 3, T1c prostate cancer and PSA of 5
C. A 73-year-old male with 3 cores <50% positive for Gleason 3 + 3, T2c prostate cancer with PSA of 9
D. A 68-year-old male with 2 cores <50% positive for Gleason 3 + 4, T2b prostate cancer and PSA of 7
View Answer
(D) Unfavorable intermediate risk patients are not considered candidates for active surveillance.
Unfavorable intermediate risk includes two or more of the following: T2b-T2c, grade group 2 or 3, PSA 10 to 20.
Grade group 1 = Gleason 6
Grade group 2 = Gleason 3 + 4 = 7
Grade group 3 = Gleason 4 + 3 = 7
Gleason group 4 = Gleason 8
Gleason group 5 = Gleason 9 or 10
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 67-year-old male is found to have 5 cores <50% positive for Gleason 4 + 4 (Gleason grade group 4), T3b prostate adenocarcinoma with PSA of 22.
What risk group does this patient belong to? What further workup is recommended?
View Answer
Very-high-risk patients with clinically localized prostate cancer have at least one of the following: T3b-T4, >4 cores with grade group 4 or 5, primary Gleason pattern of 5, or 3 or more high-risk features. High-risk features include T3a, grade group 4 or 5, or PSA >20 ng/mL.
Further workup should include bone imaging, consider pelvic +/− abdominal imaging, and germline testing (should be categorically performed in high-risk and very-high-risk patients).
Risk stratification categories for clinically localized prostate cancer include “very low,” “low,” “intermediate” (favorable and unfavorable), “high,” and “very high” risk. They determine further staging and evaluation of disease.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
An 87-year-old male with history of dementia, stroke, heart failure, and type II diabetes is found to have T2a, grade group 1 prostate cancer with PSA of 9.
What is the appropriate next step?
View Answer
Observation is appropriate in this elderly patient with asymptomatic low-risk, localized prostate cancer.
Low risk is defined by: T1-T2a, grade group 1, and PSA <10 ng/mL.
Patients with low-risk localized disease with a life expectancy of <10 years should be observed with a plan to initiate treatment only for the development of symptoms or imminent symptoms.
Prostate cancer mortality in low-risk disease is low, and local definitive therapy is not appropriate.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 71-year-old male is diagnosed with Gleason 4 + 3 prostate cancer and undergoes radical prostatectomy.
Which high-risk pathologic findings would be an indication for postoperative radiation?
View Answer
Seminal vesicle invasion, positive margin, extracapsular extension, or detectable PSA are high-risk factors and considerations for external beam radiation therapy +/− androgen deprivation therapy (ADT) in the post-radical prostatectomy setting.
ADT +/− radiation should be considered for any lymph node involvement.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Eight months after a 59-year-old male had a radical prostatectomy for high-risk prostate cancer, his PSA rises to 0.8 with a repeated PSA of 2. An F-18 fluciclovine PET/CT is obtained, and there is no evidence of distant disease. The patient states that he wishes to be aggressive and receive any possible treatment.
What is the next step?
View Answer
External beam radiation therapy +/− androgen deprivation therapy (ADT) is appropriate salvage therapy in a patient with isolated biochemical recurrent prostate cancer.
For patients with PSA recurrence after radical prostatectomy and no evidence of distant disease on imaging, salvage radiation therapy with or without ADT can be offered. Observation is another option.
F-18 fluciclovine PET/CT is more sensitive at detecting recurrent localized prostate cancer as compared to standard CT and PET scans.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 79-year-old male presents to his family physician with back pain. Imaging shows a lumbar spine lesion, a cervical spine lesion, multiple rib lesions, pelvic lymph nodes, and a lung lesion. PSA is 350 ng/mL.
What treatment should be started?
A. Goserelin acetate 3.6 mg SC monthly
B. Bicalutamide 50 mg PO daily
C. Leuprolide 22.5 mg IM every 3 months
D. Goserelin acetate 10.8 mg SC every 3 months
View Answer
(B) Bicalutamide should be initiated in this newly diagnosed high-risk castrate-sensitive metastatic prostate cancer patient.
For a patient with newly diagnosed castrate-naïve prostate cancer, GnRH agonists may initially increase gonadotropin and testosterone causing a tumor flare. For patients with spine lesions at risk of cord compression or urinary symptoms at risk of obstruction, an androgen receptor antagonist should be started prior to initiating a GnRH agonist to prevent a tumor flare.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 72-year-old male is diagnosed with de novo metastatic prostate cancer. His burden of disease includes a liver lesion and multiple bone metastases with lesions on his humerus, rib, cervical spine, and lumbar spine. He is initially started on treatment with bicalutamide followed by leuprolide acetate.
Which are the FDA-approved combination treatments with leuprolide acetate in this setting? (Choose all that apply.)
A. Abiraterone
B. Cabazitaxel
C. Docetaxel
D. Radium 223
View Answer
(A and C) Abiraterone or docetaxel combined with androgen deprivation is appropriate in this high-risk patient.
For patients with high-risk metastatic disease, combining androgen deprivation therapy with either abiraterone or docetaxel has been shown to improve overall survival.
Suggested Readings: Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377(4):352.
Gravis G, Fizazi K, Joly F. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(2):149.
James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338.
James ND, Sydes MR, Clarke NW. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387(10024):1163.
Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373(8):737.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient with metastatic castrate-resistant prostate cancer is placed on abiraterone acetate.
What is the mechanism of abiraterone?
View Answer
Abiraterone is a CYP17 (17 alpha-hydroxylase) inhibitor that blocks the production of dehydroepiandrosterone (DHEA) and androstenedione which are testosterone precursors. In addition to prostate tissue, CYP17 is found in adrenal and testicular tissue.
Potential toxicity associated with abiraterone includes adrenal insufficiency, hepatotoxicity, heart failure, electrolyte derangements, and hypertension.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
When a patient is started on abiraterone, why is prednisone also needed?
View Answer
Prednisone is needed with the use of abiraterone to mitigate potential of adrenal insufficiency.
Abiraterone inhibits CYP17 which impairs the production of 17-hydroxypregnenolone and 17-hydroxyprogesterone which are precursors to the production of cortisol.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
An 81-year-old male is diagnosed with metastatic prostate cancer with PSA of 20 and two isolated metastatic lesions to his rib and pelvis.
Which of the following is not an appropriate initial treatment option?
A. Continuous leuprolide acetate
B. Continuous degarelix
C. Intermittent leuprolide acetate
D. Radiation to bone lesions
View Answer
(C) Intermittent leuprolide acetate is not an option in patients with metastatic prostate cancer.
Intermittent androgen deprivation therapy (ADT) is an option for biochemical recurrence without evidence of metastatic disease. Intermittent ADT is considered inferior to continuous ADT in metastatic prostate cancer in terms of overall survival.
Patients with oligometastatic disease can be treated with radiation to metastatic lesions to delay systemic therapy and associated side effects.
Suggested Readings:
Klotz L, O’Callaghan CJ, Ding K. A phase III randomized trial comparing intermittent versus continuous androgen suppression for patients with PSA progression after radical therapy: NCIC CTG PR.7/SWOG JPR.7/CTSU JPR.7/UK Intercontinental Trial CRUKE/01/013 (abstract #3). J Clin Oncol. 2011;29:7s.
Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): Five-year results of a randomized phase II trial [Abstract]. J Clin Oncol. 2020;38(suppl 6; abstr 10). Abstract available online at https://meetinglibrary.asco.org/record/184100/abstract
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 68-year-old male had a radical prostatectomy for Gleason 4+ 2, localized prostate cancer. Five years later, he is diagnosed with high-risk metastatic disease and offered treatment with androgen deprivation therapy plus either docetaxel or abiraterone. After starting combination therapy, he returns to clinic 1 month later, and his blood pressure is 190/90, and he is found to have a potassium of 2.9.
Which combination did this patient initiate based on nature of these side effects?
View Answer
Androgen deprivation therapy + abiraterone; and abiraterone is responsible for this patient’s profound hypertension and hypokalemia.
Abiraterone blocks CYP17 resulting in cortisol deficiency. In the setting of low cortisol, the hypothalamic-pituitary-adrenal axis is upregulated, increasing adrenocorticotrophic hormone (ACTH). Higher ACTH levels can lead to increased mineralocorticoids causing hypertension, hypokalemia, and/or edema. Administration of a glucocorticoid such as prednisone 5 mg PO daily can reduce the risk of these side effects.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 71-year-old man has metastatic prostate cancer to bone. He initially responded to androgen deprivation therapy + bicalutamide but now has rising PSA with doubling time of 7 months and adequately suppressed testosterone level. Imaging shows slowly enlarging retroperitoneal lymph nodes.
What is the next step in management?
View Answer
Commence with bicalutamide withdrawal in this patient with newly developing castrate-resistant prostate cancer.
Patients with castration-resistant prostate cancer on antiandrogen therapy may biochemically respond to antiandrogen withdrawal.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 65-year-old man has metastatic castration-resistant prostate cancer and slowly worsening back pain. PSA is rising on Lupron, abiraterone, and prednisone. Imaging shows multiple bone lesions in spine but no cord compression or other sites of disease.
What is the next step?
View Answer
Radium-223 is a good option for metastatic castrate-resistant prostate cancer patients with bone-only disease and can reduce bone pain and skeletal events as well as improve overall survival.
Abiraterone should be stopped prior to starting radium-223 given concern for higher rate of adverse events or death when combined.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient has castration-resistant prostate cancer with metastases to bones, liver, and lung. ALT and AST are three times upper limit of normal. PSA is rising on leuprolide with a 2-month doubling time.
What is the next step in treatment?
View Answer
For patients on ADT who experience rapidly progressive or visceral disease, consider upfront chemotherapy with docetaxel.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient with metastatic prostate cancer on leuprolide is noted to have a rising PSA with a 11-month doubling time. He is asymptomatic.
What cell-based therapy should be considered?
View Answer
Sipuleucel-T should be considered in this patient with slow disease progression (PSA doubling time > 10 months) and minimal cancer-related symptoms.
Sipuleucel-T is an autologous cellular immunotherapy product, consisting of peripheral blood mononuclear cells activated ex vivo with a recombinant fusion protein (PA2024) that is designed to induce an immune response against PAP, a prostate cancer antigen.
Although its use was associated with overall survival benefit, sipuleucel-T generally does not decrease serum PSA.
Suggested Readings:
Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 68-year-old man has metastatic castration-resistant prostate cancer metastatic to bone. He initially responded to androgen deprivation therapy + docetaxel but subsequently progressed and was switched to enzalutamide. After 6 months, he has new painful bone metastases, enlarging lymphadenopathy, and rising PSA.
What is the most reasonable next systemic therapy?
View Answer
Cabazitaxel is the most appropriate next therapy in this patient after enzalutamide.
In metastatic castrate-resistant prostate cancer, third-line cabazitaxel was shown to be superior to switching from enzalutamide to abiraterone (or vice versa) in the phase III CARD trial.
Cabazitaxel was generally well tolerated, though important side effects included fatigue, diarrhea, neuropathy, and cytopenias.
Suggested Readings:
de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381:2506.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 73-year-old man with a history of dyslipidemia, arthritis, seizure disorder, diabetes, and hypertension is considering systemic therapy for castration-resistant prostate cancer (CRPC).
Which of his comorbidities should be treatment considerations when choosing between abiraterone and enzalutamide?
View Answer
Seizure disorder, diabetes, and hypertension may pose therapeutic challenge in this patient when considering enzalutamide or abiraterone for CRPC.
Seizure disorder: Enzalutamide may lower the seizure threshold. Patients with predisposition to seizure were excluded from clinical trials.
Diabetes: Hyperglycemia is common on both enzalutamide and abiraterone/prednisone.
Hypertension: Uncontrolled hypertension is a contraindication to starting abiraterone.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 60-year-old man has metastatic castration-resistant prostate cancer that has progressed after docetaxel, abiraterone, enzalutamide, cabazitaxel, and radium. His sister has a known BRCA2 mutation.
What targeted therapy may benefit him after somatic tumor sequencing?
View Answer
Men with BRCA2 mutations appear to benefit from PARP inhibition.
In particular, olaparib was shown to be superior to second-line hormonal therapy (abiraterone or enzalutamide) in the phase III PROfound trial. PARP inhibitors are not yet FDA approved in this setting, and their use is considered off-label.
Germline BRCA2 mutation is the genetic event associated with the highest risk of prostate cancer.
Suggested Readings:
Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382:2091-2102.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 71-year-old man presents with lower back pain. Imaging shows a T10 lesion impinging on the spinal cord. Biopsy demonstrates prostate adenocarcinoma.
What medication should be started prior to initiating androgen blockade with leuprolide?
View Answer
Antiandrogens (ie, bicalutamide) to prevent potential disease flare.
Initiation of GnRH agonists causes a transient flare of luteinizing hormone that can temporarily drive tumor growth. Patients with concern for cord compression should first be started on antiandrogens (ie, bicalutamide) to prevent potential worsening of compression.
Suggested Readings:
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
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