W1 Prostate Cancer And Elevated PSA (Joey) Flashcards
Prostate anatomy review
Where does prostate cancer usually arise?
Where does BPH occur?
Why do men with prostate cancer not always present with urinary symptoms ?
The vast majority of Prostate Cancers (aka “PCa”) arise in the “Peripheral Zone” (PZ) — think PCP (Prostate Cancer Periphery)
Additionally, since the PZ is relatively distant f/the urethra in men, men w/ PCa often do not have urinary symptoms, unless it’s super far progressed
BPH in the transitional zone, closer to the urethra so present with urinary symptoms sooner
What is prostate cancer? Of which cells?
What type is the most common?
Where does it fall in cancers worldwide
Uncontrolled malignant growth of prostate cells, most often of the glandular cells of prostate
In general when discussing Prostate Cancer, we are discussing the most common type of prostate cancer, “Prostatic Adenocarcinoma”
2nd most common cancer in males worldwide
Prostate cancer is very indolent, slow growing. 5-year survival rate is 98%
Risk factors (slide 5)
What is the number 1 risk factor for prostate cancer?
—age
—⭐️family history, 1st degree relatively most highly a/w increased risk ⭐️
—African Americans have a high risk
—smoking
—begin screening at 40-45
—high animal fat diet
—TRT actually doesn’t increase risk, especially if you’re just normalising their levels.
—5 alpha reductase inhibitors: inhibits PSA so often detect cancer later in pts that take this
Prostate cancer
Clinical diagnosis age
—diagnosed in men >40 years old
—screening between 65-74 years old.
Prostate cancer presentation
If symptomatic:
New or worsening ______
______ pain
Elevated ______ over ______
Note that clinical manifestations of Prostate Cancer are frequently absent at time of diagnosis
New of worsening LUTS = lower urinary tract symptoms
Bone pain, rarely (LBP, hip pain) 🦴
Elevated PSA, if its >4, start to think cancer
Normal is roughly 0-4
What is PSA?
In which 4 circumstances could it be elevated ?
PSA is a glycoprotein produced
exclusively by prostate cells (healthy and cancerous prostate cells)
PSA can be elevated
—prostate disorders, BPH
—UTI
—post ejaculation
—bike riding, perineal trauma
Specific for prostate but not for prostate cancer
PSA values what’s normal?
Although highly individual, a PSA cutoff of > ______ is a benchmark for ______ screening
While the standard “normal” PSA range is 0 ng / dL - 4.0 ng / dL, > PSA is often viewed in the context of an individual pt’s PSA compared to the norm of their age group (see above chart ) and their individual “norm” (often compared to the pt’s prior year’s baseline PSA)
■ A PSA cutoff of > 4 is often used as a standard “benchmark” across multiple specialities for consideration of further Prostate Ca screening, w/u, referral to Urology (as > 4 is where sensitivity & specificity for PCa becomes > clinically significant across all groups)
AUA also recs that in general a PSA >2 in men <50 yo is abnl
PSA > 10 is much more highly correlated w/ PCa risk (tho still may be normal, like 2/2»_space;> BPH)
Notes on PSA screening
What can elevate PSA?
How does this affect the practice of DRE
Elevated PSA should be confirmed via ______ x ______ weeks later
● PSA may also be elevated in pts w/ recent perineal trauma like bike riding, recent sexual activity (past 72 hours), and may be further > in those who recently participated in receptive anal intercourse, post DRE
○ Clinical significance of DRE on risk of falsely elevating PSA to a clinically significant degree is debated, but ideally if you’re going to test the PSA, still best practice to screen the PSA prior to doing DRE
○ Elevated PSA should be confirmed via a repeat screen a few wks-mo (often > 1-2 mo) later
○ **In general, it is NOT recommended to screen PSA in pts w/ significant recent urethral / prostate / rectal manipulation (like after cystoscopy & colonoscopy in the past month, TURP in past 3mo), pts w/ active voiding sx from b/l (like in suspected active prostatitis) unless these sx are PERSISTENT, as during transient prostatic conditions, the PSA will often return significantly elevated, and may lead to referral to Uro / a bx that may not be necessary
○ This rings true as well for pt’s w/ recent perineal trauma, bike riding, recent sexual activity (all sexual activity), in these pts it’s ideal to wait at least 72 hours to test the PSA
Screening — DRE
What is normal? What is abnormal?
Why is a DRE not reliable for detecting cancer?
Abnormal” DRE findings may include feeling prostatic nodules, induration, or asymmetry (norm is often symmetrical, soft to moderately firm, tends to get more moderately firm w/ age)
- Prostate cancer may not be initially detectable by DRE alone, as DRE may often only detect tumors in the
posterior and lateral aspects of the prostate gland (the regions of the prostate palpable via rectum)
Abnormal” DRE findings may include feeling prostatic nodules, induration, or asymmetry ^ these raise suspicion
A firm fixed nodule could be in a different zone so you could miss it completely on DRE
Prostate cancer
What is the diagnostic gold standard?
Diagnosis:
GOLD STANDARD: trans-rectal guided ultrasound: Prostate Biopsy
● YOU NEED TISSUE for histological evaluation to dx prostate ca, which is achieved via prostate bx (cannot dx prostate ca w/ PSA, DRE, or imaging alone, only help w/ screening / risk stratification)
Transrectal prostate biopsies are the most common, however transperineal bx occur too
Common risks of TRUS prostate biopsy
% of patients that develop sepsis
Limitations of biopsy
Common Risks of TRUS (trans-rectal ultrasound) Prostate Biopsy:
○ Post-Biopsy Infection (occurs in 1-11% of pts, highly
DIAGNOSTIC GOLD variable) w/ exs: Focal Prostatitis, all the way up to Sepsis
Up to 1-3% of pts develop sepsis
Urosepsis from prostate biopsy may even be fatal!!
Limitations of biopsy
—May miss dz (clinician experience performing bx, ability to
obtain advanced imaging pre-px, anterior prostatic dz, etc)
—Transperineal bx has < infx risk, but may miss dz (experience)
—A negative biopsy does not mean you do not have PCa
Prostate cancer
TNM staging, Gleason score, grade groups
Which score and under is less aggressive?
Which score an over is more aggressive?
> Gleason score is a/w > risk of clinically aggressive course, but other factors like stage play a role too
○ Roughly, gleason 6 is much LESS likely to invade the SVs, spread to LN, or met to 3* sites (it basically never does)
○ Roughly, Gl 7 is > likely to invade, ≥ Gl 8 MUCH > likely to
Do not memorize any of the above on this slide (or the TNM staging / Gleason Score slide at end), but the following good to know in your clinical practice:
● Roughly, Gleason 6 prostate cancer is overall less aggressive (overall considered unlikely to spread to site beyond prostate),
Gl 7 and > = more aggressive
● Stage 4 often needs more aggressive tx than focal therapy / resection alone, like ADT, chemo (often a multi-disciplinary approach), & tx often not curative
Prostate metastatic disease
Which top 3 sites?
Metastatic Prostate Cancer: brain, LNs, bone
PCa has spread beyond the local LN to tertiary sites (aka
“distant” mets like rectal/bladder invasion, bone, brain)
○ Most common extra-pelvic initial sites of Mets are:
Retroperitoneal LNs, Bone (spine, pelvis, femur)
Prostate cancer common initial treatment modalities
What are the two side effects / what does the patient experience after treatment?
—surgical resection: radical prostatectomy.
—Patients will often have ED after prostate removal, nerves along cavernosum attached to prostate, they get stretched
—also tend to have some degree of immediate SUI
—radiation therapy
Post-Treatment Follow Up & Surveillance
What are you monitoring post removal of the prostate?
For how long?
PSA is super helpful post prostate removal
typically patients are monitored post initial treatment via regular PSA screening
Most commonly PSAs are first re-screened 3 mos post initial treatment, then q 3-12 mo f/ there for the first 1-2 yrs
○ If PSA dropping to very low or “undetectable” (PSA <0.1), may be spaced out further to q 12 mo definitively (PSA is
often eventually spaced out q yr 2 yrs post-tx if the PSA became undetectable & trends remained flat for > 2- 5 yrs)
Prostate cancer treatment: ADT and Chemo
What is ADT?
What is the agent?
What is the MOA?
Androgen Deprivation Therapy (ADT):
GNHR agonist: Lupron
see below for MOA
Chemotherapy:
—Rarely used in PCa (as often not helpful, PCa is 1*ly androgen dependent ), but sometimes as a last-line salvage tx in CSPC & refractory MCRPC, even more rarely used palliatively
Lupron MOA
Leuprolide is a synthetic 9-residue peptide analogue of gonadotropin-releasing hormone (GnRH). As a GnRH mimic, leuprolide is capable of binding to the GnRH receptor (GnRHR) and inducing downstream modulation of both gonadotropin hormone and sex steroid levels. Prolonged activation of GnRHR results in significant downregulation of sex steroid levels, which is primarily responsible for the clinical efficacy of leuprolide in diverse conditions, including advanced prostate cancer, endometriosis, and central precocious puberty
Prostate cancer: active surveillance
How often should you be re-biopsied?
Regardless of PSA or DRE findings, on active surveillance pts typically get
re-biopsies at least every 2 years
Interesting read: prostate cancer mortality and survival… what to do in otherwise healthy males
Prostate screening, work up risks
Main risk during the work up?
Treatment morbidity includes some degree of ______ and ______
WORKUP in general, while down the road may be life saving, also has risk/benefit (anxiety, cost )
—Workup morbidity includes anxiety, cost, UTI (prostatitis / prostate abscess / urosepsis)
—Urosepsis on it’s own may actually be a considerable morbidity & mortality risk !
Treatment morbidity often includes at least some degree of urinary incontinence, ED
Recent Notable Healthcare Body Recommendations on Prostate Cancer & PSA Screening
…..light reading…
Best practice regarding screening and when
In general, age range 55 - 69 is where multiple groups agree there may be the most benefit for PCa screening
For pt’s w/ family hx of PCa or genetic predisposition to PCa, screening in this age group (or even earlier depending on the risk factors) can be even more beneficial in terms of morbidity and mortality
Prostate cancer take homes [know well!]
—screening most beneficial in men aged _______
—definitive diagnosis with _______
—standard threshold for evaluation of PCa is with a PSA of _______
—PSA is highly useful in _______
—General consensus is that Prostate Ca screening may be most beneficial in men age 55 - 69 yo (risk / benefit )
—PCa may only be definitively diagnosed via tissue biopsy
—Screening and treatment of prostate cancer is an individualized decision for the pt, patient education and shared decision making throughout the entire process is paramount
—Standard” threshold for further evaluation / workup of PCa / risk in the community is thought to be PSA > 4.0 ng /
dL
—The best available evidence from randomized trials found that screening has at most a small benefit in < prostate
cancer mortality. PSA screening has no benefit in reducing overall mortality
—While PSA screening and interpretation is complicated, it remains a useful tool in screening for prostate cancer in high risk patients, and is highly useful in post-treatment surveillance
