- Age --> >70% of cases happen in those ages 65 and older

- African American or Jamaican descent

- Family history in 5-10% of cases

- Genetics play a role through BRCA 1 and BRCA 2 expression

- Diet high in saturated fat

- Risk of dying increases with body weight

- Prostate cancer is the most common cancer in men, but NOT the most deadly

What is significant regarding Prostate Specific Antigen (PSA?)

- Protein made by the prostate gland

- Elevated in BPH, infection, prostatitis, cancer, post-ejaculation

- Controversy over normal value and use as a screening tool

- Value of <4ng/ml is normal, but cancer can be seen at this level also

- Some studies recommend using 2.5 or 3ng/ml as a cut-off

- > 20ng/ml is significantly elevated

- Useful for monitoring response to tx

- Usually none

- If symptomatic, problems with urination (starting/stopping/urgency), and ED

- Metastatic disease present with pain in lower back, pelvis, and upper thighs

DRE - MD feels for lumps or rough areas

PSA - controversial > 20ng/ml suspicious

TRUS - trans-rectal ultrasound, probe inserted through rectum to take sonogram

Biopsy - 2 biopsies from separate areas of prostate

Bone scan, CT, and MRI - To check for metastases

- Sum of the scores (1-5) assigned by pathologist to each sample from biopsy

- Max score = 10

- Prognostic indicator

- Gleason of 8-10 shows highest risk of death from prostate cancer

- Gleason 2-4 lowest risk of death

Stage I - Localized to prostate, caught by chance, not seen or felt

Stage II - Localized to prostate, may be seen or felt

Stage III - Spreads just outside of prostate, not found in lymph nodes

Stage IV - Cancer in lymph nodes or bones

Using the diagnostic principles of prostate cancer, what kind of work-up would be needed if......

A.  A patient had a life expectancy of < 5 years AND is ASYMPTOMATIC

B.  A patient had a life expectancy of > 5 years OR is SYMPTOMATIC

A.  No additional work-up beyond DRE, PSA, biopsy for gleason score unless Gleason score is 8+ or "bulky" disease

B.  Deserves further work-up such as....
- Bone scan

- Pelvic CT scan or MRI

Stage I or II (Localized)- Active surveillance OR radiation OR surgery (radical prostatectomy)

Stage III (Locally Advanced) - Radiation with 4-6 months ADT

Stage IV (Metastatic) - Radiation + 4-6 months ADT if only lymph nodes; long-term ADT if distant metastases

- Active monitoring of disease with expectation to intervene if cancer progress

- DRE and PSA q6-12 months, and needle biopsy every 6-18 months as indicated

Appropriate Candidates: 

- Low risk cancer

- Gleason of <8, and <50% of prostate biopsies have cancer + PSA < 10-15 ng/ml

- Short life expectancy (<10 years)

Advantages:

- Retain QOL

- Equal in life expectancy to other more drastic measures

- No SE's b/c of treatment

Disadvantages: 

- Missed opportunity of care, risk of progression, frequent follow-up visits, subsequent treatment may be more intense, uncertain of natural history of prostate cancer

- LHRH or GnRH analog

- Add anti-androgen

- Withdraw anti-androgen

- Ketoconazole

- Docetaxel/prednisone

- Mitoxantrone/prednisone

*This is if we even decide to treat the cancer*

- ADT is use of hormonal therapies to block synthesis of dihydrotestosterone

- First line for symptomatic advanced disease or metastatic disease

- Continued indefinitely

- Start chemo after ADT failure

- When EXACTLY to start is controversial

- Doxetaxel regimens preferred (with prednisone x 3 weeks or with estramustine x 3 weeks)

- Mitoxantrone used for pain but doesn't help survival in patients

- Docetaxel continued until disease progression

- Mitoxantrone continued until lifetime max dose

- Suppress negative feedback release of FSH and LH, reducing testosterone production in testes

- Can be considered "medical castration"

- Equal in efficacy to orchiectomy

- Leuprolide 7.5mg IM monthly, Eligard is same but SQ

- Goserelin --> basically same as Leuprolide but 3.6mg SQ qmonth

If patient can't take LHRH:

- Go with GnRH analog

- Degarelix.....must have.....

- Risk of neurological compromise due to metastasis

- Uretral or bladder outlet obstruction from CA

- Severe bone pain from mets in spite of narcotics

- 240mg injection SQ (separate) during first month, then 80mg SQ q28 days

- Used to block conversion of testosterone to dihydrotestosterone

- Used after progression on LHRH analog or orchiectomy alone

- NEVER USED ALONE

- Used for 7 days when starting LHRH in patient w/metastatic disease to prevent tumor "flare"

SE:  soft stools, hormonal effects

- Bicalutamide (Casodex) --> 50mg daily

- Also causes HTN, disulfiram-like rxn

- Technically approved for only post-orchiectomy

**Finasteride can make cancer more aggressive in those who actually have it**

- Blocks production of multiple hormones, like testosterone, in the adrenal cortex

- 400mg PO TID +/- hydrocortisone to prevent adrenal gland suppression

- Best absorbed emtpy stomach but likely take with food to reduce upset GI

- Used to postpone chemo

- In combo with prednisone 5mg BID, this is gold standard for metastatic prostate cancer

- 75mg/m2 IV q 3 weeks

- Edema/fluid retention, premedicate with dexamethasone

- SE:  Mucositis, myelosuppression, alopecia, hepatic issues --> do not administer if AST/ALT < 1.5x ULN, or ALP > 2.5x ULN

Dose:  280mg TID days 1-5 q21 days with Docetaxel

- Not commonly used, keep in refridgerator

- Calcium reduces absorption

- Causes edema, gynecomastia, leukopenia, THROMBOEMBOLISM

- Anthracyclinone = cardiotoxic

- Second line after docetaxel

- 12mg/m2 IV q21 days

- Dark blue, shows up green in bodily fluids

- Myelosuppression

- N/V is mild

- Mucositis

- Alopecia

- Adjust for bili, not for renal

- Max lifetime dose 140mg/m2

Bone mets - prostate cancer metastasizes to bone, can be mild pain in lower back, hip, or spine, can cause spinal cord compression!

- Must treat aggressively

- Risk increases with ADT

- Dexamethasone and radiation can be used to treat the pain, opioids also used

- Zoledronic acid 4mg over 15 minutes qmonth

- Prevents bone loss but not mets

- bone pain and flu-like sx are adverse effects

- CI if Scr > 3, > 1 in normal renal function, > 0.5 g/dl in CKD

- Calcium and Vitamin D is a must, could give Alendronate also

- Need to be screened for diabetes and other cardiovascular issues

- Must get PSA and DRE starting at age 50, age 45 if African American or high risk, or 1st degree relative of someone who has prostate issues