Flashcards in 16 Prostate Cancer Chan Deck (84):
What are some facts on prostate cancer?
Most common cancer in men. Indolent (or slow) growth pattern in early stages compared to other cancer types. AA > Whites > Asians
What is the etiology of prostate cancer?
Hormonal (increase exposure to testosterone (growth signal to the prostate)). Genetic predisposition (SRD5A2 gene). Presence of pre-malignant lesion
What does the SRD5A2 gene do?
Codes 5-alpha reductase (enzyme converts testosterone to DHT). Gene variant increases activity and may increase prostate cancer
What does the presence of pre-malignant lesions indicate?
Prostatic Intraepithelial Neoplasia (PIN) or Proliferative Inflammatory Atrophy (PIA). Precedes prostate cancer by 10 years or more. Detection of PIN requires needle biopsy. Presence of PIN does NOT cause changes in PSA level
What are the Prostate Cancer Risk Factors?
Age (~66 years). Male. Race (AA > White > Asian). Family history (One 1st degree relative = two-fold increase, two 1st degree relative = four-fold increase). Diet
How does Diet change your risk of prostate cancer?
Increase risk: high intake of dietary fat. Decrease risk: Soy (anti-carcinogen) and Lycopenes (found in tomatoes). Lack benefits - Vit E, Selenium
What are NOT considered risk factors for Prostate Cancer?
Smoking and alcohol consumption. Benign Prostatic Hyperplasia (BPH) - non-malignant condition1
What are the warning signs and symptoms of prostate cancer?
Non-specific, similar to symptoms caused by BPH. Dysuria, nocturia, anuria, hematuria. Impotence. Less firm penile errection. Advance stage disease: Anorexia, bone pain that is persistent in lower back, pelvic region or upper thighs
What did the PCPT trial show?
Finasteride (Proscar) (off label - risk reduction) = 5mg daily for 7 years. Significantly reduce prostate cancer rate detectable with biopsy by 25% vs. placebo
What did the REDUCE
Dutasteride (Avodart) (off label - risk reduction) = 0.5mg daily for 4 years. Significantly reduce prostate cancer rate detectable with biopsy by 25% vs. placebo
What are the new screening guidelines for prostate cancer?
Recommend for men age > 50 w/ average risk of prostate cancer, life-expectancy > 10 years. Men at high risk (i.e. AA, family history of prostate cancer before age 65). Men at higher risk (multiple family history < 65) - discussion at age 40.
What are the potential treatment toxicities for prostate cancer?
Incontinence. Impotence (decrease QOL). Difficult to identify indolent vs. aggressive tumor
What are the screening methods for prostate cancer?
Digital rectal exam (DRE) optional, and Prostate-specific antigen (PSA) blood test (none 100% predictive)
What are you looking for in a DRE?
Presence of lumps, hardness, and inability to move the prostate. Only 25-50% palpable mass are cancerous
What is the PSA blood test?
Glycoprotein produced by epithelial cells of prostate. Specific for the prostate, not specific for cancer. Normal ranges: 0-4 (PSA 2.6-4 requires further evaluation by biopsy. PSA > 10 suspicious for malignancy). Abstinence for 2 days prior to obtaining PSA
What do the grades in the Gleason Scale indicate?
Grades <7 (slow-growing, well differentiated tumors) = better prognosis. Grade 7 (moderately differentiated tumors). Grades 8-10 (aggressive, poorly differentiated tumors) = poor prognosis. Higher the score, the greater probability of extracapsular spread, nodal involvement and distant metastases
What is the natural history of the disease?
Indolent (slow) growth commonly seen in early stages. Spreads by local extension via the lymphatic system to regional lymph nodes or via bloodstream to other part of the body. Metastases common to the bone (80%) usually involve the lumbar spine, may also metastases to lung and liver
What is Stage I Prostate Cancer?
Non-palpable, localized, biopsy detected, high PSA
What is Stage II Prostate Cancer?
Palpable, confined to capsule (1-2 lobes)
What is Stage III Prostate Cancer?
Local extension beyond capsule
What is Stage IV Prostate Cancer?
Lymph node involvement with mets to other areas
What does Neoadjuvant mean?
Initial treatment of locally advanced tumors that are unlikely to be cured by surgery or irradiation. Goal is to reduce tumor volume
What does Adjuvant mean?
Systemic therapy following curative surgery or irradiation for tumors that have a high probability of recurrence
What does Salvage Treatment mean?
Systemic therapy in patients who have failed initial treatment
What does Palliation mean?
Treatment used only to relieve or alleviate symptoms NOT to provide cure
What are the treatment goals for prostate cancer?
Androgen deprivation or ablation (80% of tumors are androgen dependent): Maintain suppression of serum testosterone < 50 (considered castration level). Decrease symptoms. Delay progression and improve QOL
What are the treatment options for Prostate Cancer?
Expectant management or watchful waiting. Surgery (Radical Prostatectomy). Radiation therapy. Pharmacological intervention (hormonal therapy, immunotherapy, chemotherapy, clinical trials)
When should Expectant Management or Watchful Waiting be considered?
For LOCALIZED early Stage I, II tumors. Recommended for elderly men with life expectancy < 10 years, low grade disease, and slow PSA velocity
When is Surgery (Radical Prostatectomy) recommended?
Men of any age with life expectancy > 10 years, localized stage I, II tumors, high grade disease, high PSA velocity
When is Radiation therapy recommended?
For locally and advanced disease (Stage I-III) in men > 70 years of age who are NOT surgical candidates d/t other comorbid conditions. Recommended as palliation therapy in patients whose tumor extended beyond the prostate (Stage IV). Recommended as adjuvant therapy after surgery in patients with (+) margin (residual disease)
What are the advantages of Radiation therapy?
Decreased risk of urinary incontinence and sexual dysfunction vs. surgery
What are the complications with Radiation therapy?
Impotence (30%), rectal (proctitis) and bladder (cystitis) symptoms
What are the side effects with Radiation Therapy?
Fatigue, skin reactions or irritation to the treated areas, frequent and painful urination, rectal irritation or bleeding, and N/V/D
What types of pharmacological intervention can be used?
Hormonal therapy or Androgen deprivation therapy (ADT). Treatment dependent on tumor being localized, or with advanced disease (PSA recurrence or mets disease)
When is Chemotherapy treatment indicated?
For metastatic disease and HRPC
What is 1st line chemotherapy for prostate cancer?
Docetaxel w/ Prednisone. Can use Cabazitaxel w/ Prednisone after failure with Docetaxel
When is Immunotherapy indicated in prostate cancer?
Indicated for less advanced asymptomatic or minimally symptomatic metastatic HRPC disease
What are the guidelines for Immunotherapy use?
Good performance status (ECOG 0-1). Estimated life expectancy > 6 months. No visceral disease (mets to lung and/or liver). No symptoms or with minimal symptoms
What are the advantages of Hormonal Therapy?
Least toxic anticancer treatment
What are the disadvantages of Hormonal Therapy?
Delayed clinical response (require 6-8 weeks of continual therapy), efficacy depends on maintenance therapy and patient compliance. Hormonal receptor (PR) status is NOT useful in the treatment of prostate cancer
What are the first line hormonal therapy choices?
Orchiectomy, GnRH agonist +/- Anti-androgen
What is Orchiectomy?
Surgical removal of testicles (surgical castration). Works by eliminating production of testosterone (rapid decrease in testosterone level to castration level < 50 over 24-48 hours)
What are the side effects of Orchiectomy?
Impotence. Hot flashes
What are the GnRH agonists used?
Leuprolide. Goserelin. Histrelin
What are the general characteristics of GnRH Agonists?
As effective as Orchiectomy in decreasing testosterone to castration level (medical castration). Has a delay clinical response (about 2-4 weeks after first injection). With continued therapy decrease in testosterone level can be maintained for up to 5 years. Psychologically easier to tolerate than surgical castratoin
What labs need to be monitored with GnRH Agonists?
What is the dosing of Leuprolide (Lupron Depot) like?
7.5mg Qmonth, 22.5mg Q3months, 30mg Q4months. Administered by deep IM intragluteally
What is the dosing of Leuprolide (Eligard Depot) like?
7.5mg Qmonth, 22.5mg Q3months, 30mg Q4months, 45mg Q6months. Administered by SQ injection
What is the dosing of Goserelin (Zoladex) like?
3.6mg Qmonth, 10.8mg Q3months. Administered by deep SQ pellets injection into the upper abdominal area
What are the two GnRH Agonists that are used the most?
Leuprolide (Lupron, NOT Eligard). Goserelin (Zoladex)
What is Histrelin (Vantas)?
GnRH Agonist. Implant (50mg over 12months). Requires SQ surgical implantation. Suppression of testosterone level maintained up to 2 months following removal of first implant
What are the common ADRs with GnRH Agonists?
Hot flashes, Gynecomastia, Loss of libido, Impotence, Injection site irritation. Tumor-flare
What is Tumor-flare with GnRH Agonists?
Bone pain, weakness, and increase difficulty urinating (common with 1st few weeks of treatment, symptoms usually resolved after prolong administration. DO NOT discontinue for tumor-flare)
How can Tumor-flare be prevented?
By pretreatment with anti-androgen (starts 2-4 weeks prior to or at same time with GnRH agonist, and continue for up to 7 days after the start of GnRH agonist in patients with advanced disease)
What are the long term side effects with GnRH Agonists?
Increased risk DM, insulin resistance. Increased CV risk, alterations in lipids, cholesterol. Increased risk of osteoporosis and incidence of clinical fracture. Obesity
What is Degarelix (Firmagon)?
GnRH ANTAGONIST. Similar to GnRH Agonists, but without the Tumor-Flare
What are the ADRs with Degarelix (Firmagon)?
Similar to GnRH Agonists
What is used for the treatment of Osteoporosis and Skeletal-Related events?
IV Bisphosphonates (Zolendronic acid (Zometa) or Pamidronate (Aredia)
What is the MOA of Bisphosphonates?
Binds to bone surface and inhibits osteoclast bone resorption
What labs need to be monitored while on Bisphosphonates?
Monitor SCr (renal dosing adjustment), Calcium (cause hypocalcemia)
What are the ADRs with Bisphosphonates?
Osteonecrosis of Jaw (ONJ)
What are the indications for Bisphosphonates?
Treatment of mets bone lesion for all solid tumor = Zometa 4mg IVPB over 15-30 minutes Q3-4 weeks. Treatment for osteoporosis = Zometa 5mg IVPB over 15-30 minutes once a year
What is Denosumab (Prolia, Xgeva) used for?
Osteoporosis. Monoclonal antibody RANK ligand inhibitor - binds to RANKL signaling molecule that stimulates function and survival of osteoclasts. SQ upper arm, upper thigh or abdomen
What labs need to be monitored with Denosumab?
Calcium (cause more hypocalcemia vs. Zometa). NO renal adjustment needed
What are the ADRs with Denosumab?
Osteonecrosis of Jaw (ONJ)
What are the indications for Denosumab?
Treatment of androgen deprivation (hormonal therapy) - induced bone loss = 60mg Prolia SQ Q6 months. Treatment of skeletal-related events in bone mets from solid tumor = 120mg Xgeva SQ Q4 weeks
When are Antiandrogens (Androgen Receptor Blockers) recommended?
For use in metastatic prostate cancer (Stage IV) in combination with GnRH agonists for complete androgen blockade (CRB)
What is the MOA of ntiandrogens (Androgen Receptor Blockers)?
Blocks the access of Dihydrotestosterone (DHT) to androgen receptor within the prostate cancer cells
What are the ntiandrogens (Androgen Receptor Blockers) used?
Bicalutamide (Casodex). Flutamide (Eulexin). Nilutamide (Nilandron)
What are the ADRs with ntiandrogens (Androgen Receptor Blockers)?
DM (w/ GnRH agonist), CV - peripheral edema. Hot flashes. Diarrhea (F > B > N)
What needs to be monitored while on ntiandrogens (Androgen Receptor Blockers)?
LFTs. Caution in patients with liver impairment
What is the rationale behind Combined Androgen Blockade (CAB)?
Interfere with multiple hormonal pathways to completely eliminate androgen action
What is the CAB used?
GnRH agonist or Orchiectomy PLUS Antiandrogen. No proven benefits over castration alone in patients w/ metastatic disease
Where is CABs place in therapy most beneficial?
Prevention of tumor-flare in patients with advanced metastatic disease (short term up to 7 days). All other patients may be started on GnRH agonist monotherapy, Antiandrogen may be added after several months if androgen ablation is incomplete
What is Abiraterone acetate (Zytiga)?
Second line hormonal therapy. Potent, selective and irreversible inhibitors of CYP 17 enzyme required for androgen biosynthesis expressed in testicular, adrenal, and prostatic tumor tissues. Inhibits formation of testosterone precursors DHEA and androstenedione
When is Abiraterone acetate (Zytiga) indicated?
Mets castration resistant or recurrence prostate cancer (CRPC) previously treated with Docetaxel (chemotherapy)
What does Abiraterone acetate (Zytiga) need dose adjustment?
Hepatic. Moderate impairment = require dose adjustment. Severe impairment = avoid use
What are the ADRs with Abiraterone acetate (Zytiga)?
Adrenocortical insufficiency, hepatotoxicity, CV (HTN, fluid retention, decreased K)
How do Estrogen Derivatives work?
Inhibits testosterone levels by blocking the production of gonadotropin releasing hormones (GnRH) which ultimately stops the production of testosterone from the testes
What are the estrogen derivatives approved for palliation?
Estradiol (Estrace). Esterified estrogens (Estratab)
What are the ADRs with Estrogen Derivatives?
Thromboembolism, Gynecomastia, Impotence. Monitor LFTs and lipid panel. Avoid in severe liver impairment
How would low dose steroids help?
Negative feedback mechanism on secretion of adrenocorticotrophic hormone (ACTH) in the pituitary leading to inhibition of androgen synthesis in the adrenal gland
What are the low dose steroids used?