Prostate Cancer (3) – Flashcards
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what age does prostate cancer usually affect men?
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>40 yo
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why does incidence of prostate cancer increase with each decade of life beyond 40 years old?
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lifetime exposure to testosterone
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risk factors for prostate cancer
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age race family history genetic mutations smoking diet environmental/exposures
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what is the normal production of testosterone
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hypothalamus releases LHRH which triggers pituitary to release LH, FSH, and ACTH LH,FSH trigger testes to release testosterone ACTH triggers adrenal glands to release androgens testosterone and androgens are metabolized by 5alpha reductase to DHT which has a higher affinity to the androgen receptor and gets incorporated into cell nucleus to drive proliferation, differentiation, etc. of normal prostate cells
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most cases of prostate cancer are what type?
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adenocarcinoma
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in early stages of prostate cancer, what promotes tumor cells to proliferate?
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androgens
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how can prostate cancer spread?
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local extension lymphatic drainage hematogenous dissemination
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prostate cancer common sites of metastases
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*skeletal* lung liver brain adrenal glands
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what are the 2 ways we screen for prostate cancer?
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digital rectal exam (DRE) prostate specific antigen (PSA) testing
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what are we looking for with a DRE?
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asymmetric areas induration nodules detect tumors in the posterior and lateral aspects of the prostate
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what is PSA, and is it specific to prostate cancer?
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a glycoprotein produced by prostate epithelial cells NOT specific to prostate cancer
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what can PSA be used for?
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detecting prostate cancer at early stages predicting outcome for localized disease monitoring disease-free status monitoring response to androgen-deprivation therapy or chemotherapy for advanced-stage disease
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factors that interfere with PSA testing
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infection recent instrumentation ejaculation trauma BPH prostitis urinary retention 5alpha reductase inhibitors ketoconazole saw palmetto
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when should patients begin prostate cancer screening according to NCCN?
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45 yo
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how often should patients undergo screening according to NCCN?
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if PSA <=1 retest every 2-4 years otherwise every 1-2 years
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when should screening be D/C according to NCCN?
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life expectancy <10 years- we don't need to screen someone who has a comorbidity that will out compete the cancer
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prevention of prostate cancer
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dietary changes weight loss smoking cessation
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which medications can be used to prevent prostate cancer?
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5alpha reductase inhibitors: finasteride dutasteride
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what have finasteride and dutasteride been found to affect?
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decrease incidence of prostate cancer did not decrease prostate related deaths increase incidence of more aggressive prostate cancer
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side effects of finasteride and dutasteride
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gynecomastia decreased libido erectile dysfunction
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who should we consider for use of 5alpha reductase inhibitors?
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asymptomatic men with PSA <=3 must weight benefits vs. risk
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was there evidence of effective chemoprevention with selenium and vitamin E?
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no
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clinical presentation of early stage prostate cancer
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asymptomatic
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clinical presentation of advanced stages
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*Micturition issues*- most specific for prostate cancer Impotence Lower extremity edema Anemia or pancytopenia Unexplained Weight loss Bone Pain
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what is the Gleason score?
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prognostic value primary and secondary pattern observed are assigned a score (range of each 1-5). These scores are then added to yield a total score
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how do we actually stage prostate cancer patients?
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consider the TNM, PSA, and Gleason score to stage into groups I-IV
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what is important to consider when deciding treatment of prostate cancer?
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estimated life expectancy
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what is "observation?"
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monitoring course of prostate cancer with the expectation to initiate therapy at the time of symptom development or change in DRE or PSA that suggests symptoms are imminent goal is to maintain QoL
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who is observation most appropriate for?
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elderly men with comorbidities that will out-compete prostate cancer
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what is active surveillance?
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watchful waiting, expectant management, or deferred treatment goal is to start treatment promptly with the intention for cure
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who is active surveillance most appropriate for?
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younger men with indolent disease and older men with decreased life expectancy
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when is radical prostatectomy indicated?
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when tumor is clinically confined to the prostate in recurrence
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acute complications of prostatectomy
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hematuria, urinary retention, edema, impotence
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chronic complications of prostatectomy
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proctitis, diarrhea, cystitis, impotence, incontinence
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who is orchiectomy most appropriate for?
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men with spinal cord compression or ureteral obstruction
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when can external beam radiation be used?
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clinically localized tumors effective for palliating bone mets
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adverse effects of external beam radiation
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bladder and bowel adverse effects
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what is brachytherapy?
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implantation of radioactive beads into the prostate
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when is brachytherapy most appropriate as monotherapy vs. combo?
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monotherapy for lower risk disease combination therapy with EBRT and/or androgen deprivation therapy for higher risk disease
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complications of brachytherapy
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urinary urgency and frequency erectile dysfunction rectal pain
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what are the 2 types of androgen deprivation therapy?
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luteinizing hormone-gonadotropin-releasing hormone agonists (LHRH agonists) gonadotropin-releasing hormone antagonist (GnRH antagonist)
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LHRH agonists MOA
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Stimulate the pituitary gland to produce more luteinizing hormone (LH) resulting in an initial elevation in testosterone production (Tumor Flare) Prolonged exposure eventually leads to pituitary receptor down regulation and a down stream reduction in testosterone production
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what are the LHRH agonists?
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leuprolide depot groserelin implant triptorelin depot
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what are the adverse effects of LHRH agonists?
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Increased the risk of cardiovascular disease, sudden cardiac death, stroke, and diabetes Osteopenia Tumor flare (first 2 weeks) Hot flashes Decreased libido, impotence Fatigue Gynecomastia QT prolongation
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GnRH antagonist MOA
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Binds to GnRH receptors in the anterior pituitary gland block the receptor decrease the secretion of luteinizing hormone decrease in testosterone production *NOTE:* NO TUMOR FLARE
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what is the GnRH antagonist?
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degarelix
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adverse effects of degarelix
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Osteoporosis Elevations in LFT Fatigue Hot flashes QT prolongation Increased risk of CV disease and diabetes
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what are antiandrogens used for?
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In combination with LHRH agonist, reduces risk of tumor flare
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antiandrogen MOA
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Binds to androgen receptors and competitively inhibits binding of DHT and testosterone and prevents testosterone stimulation of cell growth in prostate cancer
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what are the antiandrogens?
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flutamide bicalutamide nilutamide
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adverse effects of antiandrogens
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Increased risk of CV disease Gynecomastia Hot flashes Diarrhea Methemoglobinemia (bicalutamide) Elevated LFTs Visual disturbances/ impaired dark adaptation (nilutamide)
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very low risk patients: tumor, biopsy results, PSA
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tumor: T1c biopsy results: -Gleason Score <6 -Disease in fewer than 3 biopsy cores -< 50% prostate cancer detected in any core PSA: <10
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low risk patients: tumor, biopsy results, PSA
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tumor: T1a-T2b biopsy results: Gleason score <=6 PSA: <10
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intermediate risk patients: tumor, biopsy results, PSA
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tumor: T2b, T2c biopsy results: Gleason score 7 PSA: 10-20
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high risk patients: tumor, biopsy results, PSA
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tumor: T3- intermediate risk with the presence of risk factors biopsy results: Gleason score 8-10 PSA: >20
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very high risk patients: tumor, biopsy results, PSA
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tumor: T3b, T4 biopsy results: -Gleason score 8-10 -primary Gleason pattern 5 PSA: any
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how do we treat very low risk patients? (20 yrs life expectancy)
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20 yrs: -active surveillance -EBRT or brachytherpay -radical prostatectomy
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how do we treat low risk patients? (10 yrs life expectancy)
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10 yrs: -active surveillance -EBRT or brachytherapy -radical prostatectomy +/- PLND
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how do we treat intermediate risk patients? (10 yrs life expectancy)
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10 yrs: -radical prostatectomy +/- PLND -ERBT +/- ADT (4-6 months) +/- brachytherapy -brachytherapy alone if favorable disease
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how do we treat high risk patients? (all patients)
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ERBT in conjunction with 2-3 years of ADT ERBT and brachytherapy +/- ADT (2-3 years)
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how do we treat very high risk patients? (all patients)
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EBRT and long-term ADT EBRT and Brachytherapy +/- long-term ADT Radical prostatectomy + PLND (patients with no fixation to adjacent organs) ADT alone
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how do we treat nodal or metastatic disease (all patients)?
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ADT alone ERBT of the primary tumor + ADT (2-3 years)
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what is often an effective change in therapy following a failed initial therapy?
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addition or removal of antiandrogen therapy
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what is hormone refractory disease?
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all hormone manipulations have been exhausted (chemo, immunotherapy) goal is palliative
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what is the gold standard for treatment of metastatic castrate resistant prostate cancer?
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chemotherapy
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which chemotherapy agents can be used in mCRPC?
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docetaxel cabazetaxel
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which chemotherapy agent has shown improved survival?
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docetaxel
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when is cabazetaxel beneficial?
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in patients who have progressed on docetaxel
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docetaxel MOA
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Promotes the assembly of mirotubules, and inhibits the depolymerization of tubulin leading to inhibition of DNA, RNA, and protein synthesis esp. good for visceral mets
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cabazetaxel MOA
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microtubule inhibitor
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what is our hormone therapy for mCRPC?
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abiraterone + prednisone enzalutamide
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abiraterone MOA
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inhibits androgen synthesis by adrenal glands, testes, and prostate tumor
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abiraterone DDI
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CYP2D6 CYP3A4
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adverse effects of abiraterone
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Fluid retention hypertension hypokalemia joint swelling hot flashes diarrhea dyspnea adrenal insufficiency cardiac disease tachycardia afib elevated LFTs
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who is abiraterone most appropriate for?
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patients previously treated with docetaxel
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enzalutamide MOA
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androgen receptor signaling inhibitor inhibits nuclear translocation of androgen receptor, DNA binding, and co-activator recruitment greater affinity for the receptor
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does enzalutamide exhibit tumor flare (aka the agonist activity)?
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no
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what is our immunotherapy option?
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sipuleucel
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what is sipuleucel?
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patient specific anticancer vaccine patients undergo 3 leukaphoresis sessions where we harvest cells that we send back to the company; their dose is prepared and they get INFUSIONS OF THOSE CELLS 2 weeks apart improved survival in mCRPC patients with minimally symptomatic disease
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adverse effects of sipuleucel
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chills fever flu-like symptoms
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why do we give patients "bone health" therapy?
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osteoporosis and osteopenia are common AE of ADT bone is the primary site of mets
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what do all patients on ADT receive for prevention of ADT-induced bone loss?
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bisphosphonate therapy: -ZA -pamidronate
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what can be used for treatment of ADT-induced bone loss?
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denosumab 60 mg SQ q6mos
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what can be given for bone mets?
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radiotherapy bisphosphonate therapy (ZA, pamidronate) denosumab 120 mg SQ q4wks
