Prostate Cancer Exam 3
What are some chemoprevention methods?
5-α-reductase inhibitors ◦Finasteride ◦Dutasteride Vitamins/Minerals ◦Selenium ◦Vitamin E
What are the leading causes of cancer and cancer related deaths in men?
Number 1 cause of cancer in men is prostate cancer Number 2 cause of cancer-related deaths in men is prostate cancer
When can siipuleucel-T be used?
Patients must have a good performance status and a life expectancy > 6 months Most common side effects ◦Fever ◦Chills ◦Headache Patients should be premedicated with acetaminophen and diphenhydramine
What is the adjuvant therapy for metastatic disease?
RT + ADT ADT
What are the treatments for locally advanced disease for high risk?
RT + ADT x 2-3 years
When is a biopsy suggested for prostate cancer?
≤ 4 ng/mL -- normal > 4 ng/mL -- biopsy suggested
When are LHRH antagonists used?
*Avoids tumor flare Fast drop in testosterone (~3 days) Equivalent to LHRH agonist for treatment of advanced prostate cancer Not studied in combination with anti-androgens
What is the screening for prostate cancer?
1) *Digital Rectal Exam (DRE) 2) Prostate Specific Antigen (PSA) ◦Not a cancer-specific marker 3) TransrectalUltrasonography (TRUS) ◦If PSA and/or DRE abnormal *No observed reduction in morbidity/mortality when DRE used without PSA monitoring
What are the PSA levels?
2.5-4 -- 20-25% likelihood prostate cancer 4-10 -- 30-35% likelihood of prostate cancer > 10 -- 67% likelihood of prostate cancer
When do we know which therapy to choose for localized disease?
Active Surveillance -repeat PSAs and biopsies ◦Should be able to detect progressive disease and then treat if necessary ◦May save the patient from unwarranted complications of treatment Radical Prostatectomy -remove entire prostate ◦Should help improve BPH symptoms (if present) ◦Lots of complications to consider ◦Urinary incontinence, erectile dysfunction Radiation Therapy ◦Complications and efficacy are similar to prostatectomy
What are some risk factors for prostate cancer?
Age -70% of cases are in males > 65 years of age Ethnicity ◦Blacks -increased incidence rate, earlier onset, higher PSA, higher Gleason score, more advanced stage upon diagnosis Family History ◦Two-fold increase in men with one 1st degree relative with prostate cancer ◦Five to eleven fold increase in men with more than 1st degree relative with prostate cancer Genetic ◦Still trying to determine and understand the various genetic alterations involved in prostate cancer Diet ◦Increased risk: Animal fat, red meat ◦Decreased risk: vegetables, soy, tomato products
What are some therapy options for metastatic disease?
Androgen Deprivation Therapy (GOLD STANDARD) Goal of therapy ◦Palliation of disease by decreasing production of testosterone ◦Continue until signs of progression Used alone or in combination with newer antiandrogens/chemotherapy ◦Docetaxel ◦Abiraterone ◦Apalutamide ◦Enzalutamide Nearly all patients will progress after 2-3 years of ADT ◦Tumor growth despite testosterone levels <50 ng/dL ◦These patients are known as castration-resistant (castration-resistant prostate cancer) *combo therapy depends on patient specifics (genetics, ECOG, etc)
What are the benefits and disadvantages of PSA screening?
BENEFITS --Simple --Objective --Reproducible --Non-invasive --Inexpensive Disadvantages --Low specificity --May be elevated in certain conditions
How prevalent is prostate cancer?
Estimated New Cases ◦174,650 in 2018 (9.9%) ◦Most common cancer in men in the U.S. Estimated Deaths ◦31,620 in 2018 (4.8%) ◦Second most common cause of cancer related death in men in the U.S. 11% of men will be diagnosed with prostate cancer at some point in their lives
How is radiation performed?
External beam radiotherapy ◦Usually used alone without androgen deprivation therapy for low risk patients Brachytherapy ◦Permanent implantation of radioactive beads ◦Delivers radiation to prostate and limits exposure of other organs ◦Utilized in low-risk cancers
What was the Prostate Cancer Prevention Trial (PCPT) and their outcomes?
Finasteride inhibits conversion of testosterone to dihydrotestosterone •N=18,882 men aged 55 and older •Finasteride 5 mg PO daily vs. placebo x 7 years •Outcomes •Prevalence of prostate cancer •18.4% vs. 24.4%; p<0.001 *aggressive tumors were more common in finasteride group 37% vs. 22.2%, p<0.001 18 year follow-up of PCPT •N=18,882 men aged over 55 •Finasteride 5 mg PO daily vs. placebo x 7 years •Outcomes •Diagnosis of prostate cancer •10.5% vs. 14.9%; p<0.001 •Diagnosis of aggressive prostate cancer •3.5% vs. 3.0%; p=0.05 •Overall survival •78.0% vs. 78.2%, p=0.46 •Must consider common side effects and quality of life Patient must determine if the benefits outweigh the risks
What are the NCCN recommendations for screening?
For PSA ≥ 4 consider biopsy in select patients
What is the risk stratification for prostate cancer?
For newly diagnosed prostate cancer, patients are stratified based on their overall risk of disease progression: ◦Clinical staging ◦PSA level ◦Gleason score ◦Number of biopsy cores with cancer ◦Imaging studies Very Low Risk Low Risk Intermediate Risk High Risk Very High Risk
What is androgen deprivation therapy?
Goal -reduce testosterone to castration levels Surgical and Medical castration are EQUIVALENT ◦Surgical castration ◦Bilateral orchiectomy = immediate drop in testosterone ◦Previous gold standard until medical castration ◦Psychologically unacceptable
What is the Gleason Grading system?
Histology / architecture of tissue ◦Primary grading = dominant histologic pattern ◦Secondary grading = bulk of remainder Graded on scale (1 -5) ◦1 = well differentiated (looks like prostate tissue) ◦5 = poorly differentiated (prostate tissue is sparse) Total Gleason Score ◦Combination of primary and secondary grading ◦Score 2-10 ◦<6 = Low grade ◦>8 = High grade
What causes prostate cancer?
Hormones ◦Lifetime exposure to testosterone ◦Testosterone = growth factor for prostate Genetic factors ◦Family history important ◦1st degree relative = 2x increase in risk ◦Autosomal dominant allele
What stages are localized disease?
I IIA IIB
What stages are locally advanced disease?
III IV
What are some causes of increased and decreased PSA levels?
Increased PSA --Benign Prostatic Hypertrophy (BPH) --Prostatitis --Prostatic manipulation (TRUS, TURP, biopsy) --Acute urinary retention Decreased PSA --5-alpha reductase inhibitors •Finasteride •Dutasteride •May reduce PSA by 50%
What is the natural history of the disease?
Localized disease starts in the prostate and then spreads Local extension ◦Through seminal vesicle to local organs/tissues Lymphatic drainage ◦Pelvic and abdominal lymph nodes most common Hematogenous dissemination ◦Skeletal metastases most common
What are the signs and symptoms of prostate cancer?
Majority of men are asymptomatic at diagnosis ◦Present with abnormal DRE and/or elevated PSA Locally advanced disease ◦Similar symptoms to benign prostate hyperplasia (BPH) ◦Impotence ◦Urination issues ◦Hematuria Metastatic Disease ◦Lower extremity edema ◦Anemia ◦Weight loss •Bone pain •Spinal cord compression
What else does testosterone do in the body?
Male sex hormone ◦Maturation of male sex organs ◦Sperm development ◦Muscle tone ◦Bone mass ◦Body hair ◦Deepens voice
What is the general screening practice for prostate cancer?
Males over the age of 50 with a life expectancy of 10 years offer an ◦Annual PSA ◦Annual DRE High risk patients (African American and/or family history) offer tobegin screening at ~40 years of age
What are the goals of treatment for prostate cancer?
Minimize morbidity and mortality ◦Cure is not always the goal Decisions have many independent variables ◦What is their risk stratification? ◦Anatomic extent of disease ◦Histologic grade of disease ◦PSA level ◦Patients general medical condition, age and comorbidities ◦Life expectancy
When can you observe prostate cancer?
NCCN Very Low Risk Elderly and/or frail patients where comorbidities will out-pace the prostate cancer Goal to maintain quality of life by avoiding non-curative treatment ◦Serial monitoring of PSA and DRE ◦Palliative androgen deprivation therapy begins when symptoms occur
Who makes screening recommendations for prostate cancer?
National Comprehensive Cancer Network (NCCN) U.S. Preventative Taskforce American Urological Association (AUA) American Cancer Society (ACS)
What is castration resistant prostate cancer (CRPC)?
Patients being managed with ADT who subsequently experience disease progression Management dependent on extent of progression
How is prostate cancer diagnosed?
Physical exam Serum chemistries / PSA Imaging ◦Bone scan ◦CT/MRI Biopsy ◦Transrectal ◦Transuretheral
What is sipuleucel-T?
Provenge Autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic CRPC Approved April 29th, 2010 1st"cancer vaccine" to win FDA approval for prostate cancer Total course of therapy consists of 3 cycles, separated by 2 weeks
What are the treatments for locally advanced disease for very high risk?
RT + ADT x 2-3 years
When is a prostatectomy performed?
Radical Prostatectomy ◦Potentially curative if localized ◦Appropriate for any tumor confined to the prostate Reserved life expectancy > 10 years ◦Significant morbidity ◦Impotence, urinary incontinence very common
When are LHRH agonists used?
Reversible medical castration Testosterone decline ~24 days Equally effective to orchiectomy Tumor flare ◦Occurs during the first week of therapy and resolves after 2 weeks ◦Increased urinary symptoms and/or bone pain ◦Initial induction of LH and FSH leading to increased testosterone production ◦Minimized by anti-androgen therapy prior to LHRH agonist administration and continuing for 2-4 weeks
When are anti-androgens used?
Similar efficacy between agents Tumor flare prophylaxis ◦Used with LHRH agonists ◦Start before LHRH agonist is administered and continue for 2-4 weeks Adjuvant therapy ◦Not efficacious when used as monotherapy ◦Combined with LHRH agonist or orchiectomy
What are some prognostic factors for prostate cancer?
Stage at diagnosis ◦Histologic grade (Gleason Score) ◦Most important ◦Poorly differentiated tumors are highly associated with regional lymph node involvement and distant metastases Tumor size Local extent of primary tumor PSA level Age at diagnosis
What types of biopsies are performed?
Transrectal biopsy ◦Thin needle through rectum to prostate ◦Transurethral ultrasound used as a guide Transurethral Resection of the Prostate (TURP) ◦Urological operation Pathology ◦>95% adenocarcinoma ◦Glandular tissue
What are factors to consider when treating localized disease?
Treatment options need to be discussed thoroughly with patients What's right for one patient may not be the correct approach for the next Factors to consider: ◦Age ◦Lifespan ◦Baseline symptoms (urinary frequency, ED symptoms, etc) ◦Patient perception of disease severity ◦Potential side effects
What are the issues with knowing when to screen?
Very controversial topic without consensus Shared decision making between patient and provider is key
What are the treatments for localized disease low risk?
active surveillance OR radiation therapy OR prostatectomy observation
What the treatments for localized disease very low risk?
active surveillance OR radiation therapy OR prostatectomy active surveillance observation
How is sipuleucel-T made?
leukapheresis to collect patient antigen presenting cells (APCs) APCs exposed to prostate cancer antigen (PAP + GM-CSF) patient is administered modified APCs
What is the treatment for localized disease intermediate risk?
prostatectomy OR RT +/- ADT x 4-6 months RT +/- ADT x 4-6 months OR observation
What are some types of medical castration?
reversible Luteinizing hormone-releasing hormone (LHRH) antagonist Luteinizing hormone-releasing hormone (LHRH) agonist Anti-androgens -Block testosterone receptor All block testosterone production LHRH also known as gonadotropin-releasing hormone (GnRH) and can be used interchangeably
What is active surveillance?
watchful waiting Younger men with indolent cancer ◦Longer life expectancy = closer follow-up *Goal to defer treatment as long as possible but begin at first sign of progression
