B/6. Incidence, symptoms and diagnosis of prostate cancer B/7. Localized prostate cancer B/8. Treatment of advanced prostate cancer Flashcards
Benign prostatic hyperplasia (BPH) VS Prostate cancer where does it occur
- BPH: Periurethral zone (lateral and middle lobes)
- Prostate cancer : peripheral zone (posterior lobe)
most common male cancer
prostate cancer
2nd most common cause of cancer-related death among males (in the US)
prostate cancer
prostate cancer risk increases with
with advancing age,
with average age at diagnosis being 66 years
Risk factors of prostate cancer
- Genetic factors (cancer risk increases x2 if a 1st degree relative is affected)
- African-American > Caucasians
- Dietary factors (‘Western diet’)
- Environmental factors
- Hormonal factors
Clinical findings of prostate cancer early VS advanced disease
- Early disease produces no symptoms
- Advanced disease may present with signs and symptom related to obstruction and irritation, incontinence, hematuria.
*Constitutional symptoms (fever, weight loss, anemia) may also be present. - Metastatic disease may present with:
*musculoskeletal pain (bone metastases)
*neurological symptoms (due to spinal cord compression), and
*lymphedema (obstructing metastases in lymphatics)
metastatic prostate cancer can present with
Metastatic disease may present with:
*musculoskeletal pain (bone metastases)
*neurological symptoms (due to spinal cord compression), and
*lymphedema (obstructing metastases in lymphatics)
advanced prostate cancer presents with
Advanced disease may present with:
* signs and symptom related to
1. obstruction and irritation,
2. incontinence,
2. hematuria.
*Constitutional symptoms (fever, weight loss, anemia) may also be present.
early prostate cancer presents with
Early disease produces no symptoms
The need to pursue a diagnosis of prostate cancer is based on
- The need to pursue a diagnosis of prostate cancer is based on
1. symptoms
2. an abnormal DRE,
3. or, more typically, a change in serum PSA.
Current guidelines recommendation for screening of prostate cancer
- annual screening with PSA assay with/without DRE, starting at age 50
- Patients with positive family history (1st degree relative) or BRCA1 mutation positivity: screening should be considered at age 40-45.
Digital rectal exam (DRE) should assess
- size
- symmetry of the gland
- surface
- tenderness
- consistency
how would prostate carcinoma feel during DRE
Carcinomas are characteristically
* hard,
* nodular,
* and irregular
Overall, 20-25% of men with an abnormal DRE have
prostate cancer
Prostate specific antigen (PSA)
- Kallikrein-related serine protease that causes liquefaction of
seminal coagulum. - Produced by both malignant and nonmalignant epithelial cells and, as such, is prostate-specific, not prostate cancer-specific.
- Prostate cancer produces more bound-PSA; results in increase of total PSA with decrease % of free-PSA
what can increase serum Prostate specific antigen (PSA) levels
- cancer,
- prostatitis,
- BPH
- post-biopsy
- trauma
- prostate massage
- post-ejaculation (levels may be elevated for up to 48 hrs).
PSA levels
< 4 ng/ml : normal range
4-10 ng/ml: grey zone, refer to urologist
>10 ng/ml : highly suspicious for cancer
>20 ng/ml : highly suspicious of metastatic cancer
Prostate cancer produces more bound-PSA; results in increase of total PSA with decrease % of free-PSA
does early detection of prostate cancer correlate with clinically beneficial outcome?
detection at an early stage does NOT necessarily correlate with a
clinically beneficial outcome (decline in morbidity or mortality due to prostate cancer).
Increased detection of prostate cancer subjects some patients to further risks associated with treatments, that may not prolong life
and have risks of morbidity.
diagnosis of prostate cancer
- image-guided needle biopsy
- Direct visualization by transrectal ultrasound (TRUS) or MRI assures that all areas of the gland are sampled: sampling should include at least 6 needle biopsies from each lobe (total of at least 12).
- PCA-3 tumor marker : may be used as adjunct to prostate biopsy; measured after prostate massage
Compared to PSA, it has lower sensitivity, but higher specificity (‘rule-in’ disease).
how many needle biopsies should be included in prostate cancer diagnosis
Direct visualization by transrectal ultrasound (TRUS) or MRI assures that all areas of the gland are sampled
sampling should include at least 6 needle biopsies from each lobe (total of at least 12).
PCA-3 tumor marker VS PSA
PCA-3 may be used as adjunct to prostate biopsy;
measured after prostate massage
PCA-3 it has lower sensitivity, but higher specificity (‘rule-in’ disease).
PSA (high sensitivity, low specificity)
most common prostate cancer type
> 95% are adenocarcinomas;
the rest are squamous or transitional cell tumors.
which organ cancers can metastasize to prostate?
- Metastases to the prostate are rare,
- but in some cases:
1. colon cancers
2. or transitional cell tumors of the bladder
may invade the gland by direct extension.
Grading of prostate cancer is done by
gleason score
(established by adding the Gleason grades of the most prevalent and the second most prevalent differentiation pattern within the biopsy (a measure of histologic aggressiveness)
Higher score indicates a worse prognosis (ranges from 2 to 10)
gleason score grades
Grade ranges from 1-5
- grade 1 : well-differentiated with microscopically uniform gland;
- grade 5 being undifferentiated cancer with no glandular differentiation.
Staging of prostate cancer TX, T0
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Staging of prostate cancer T1
T1 Clinically inapparent tumor that is not palpable or visible with imaging
T1a - tumor incidental histologic finding in < 5% of tissue resected during TURP
T1b Tumor incidental histologic finding in > 5% of tissue resected
T1c Tumor identified by needle biopsy found in one or both sides, but not palpable
Staging of prostate cancer T2
T2 Tumor is palpable and confined within prostate
T2a < 1/2 of one side
T2b > 1/2 of one side, but NOT both sides
T2c Tumor involves both sides
Staging of prostate cancer T3
T3: Extra-prostatic tumor that is not fixed or does not invade adjacent structures (locally-advanced)
T3a Extra-prostatic extension (unilateral or bilateral)
T3b Tumor invades seminal vesicles
Staging of prostate cancer T4
T4:
* Tumor is fixed
* or invades adjacent structures other than seminal vesicles such as:
*external sphincter
*rectum
*bladder,
*levator muscles
*pelvic wall
imaging modality of choice to assess prostate cancer staging
MRI
which LN involved in prostate cancer
- internal iliac node
- external iliac node
- obturator nodes
- para-aortic
where does prostate cancer metastasize to
- LN (internal iliac node, external iliac node, obturator nodes, para-aortic)
- BONE
- LUNG
- LIVER
Prostate cancer bone metastases are characteristically
osteoblastic (bone-forming) lesions
Prostate cancer bone metastases presents with
lower back pain
increased serum ALP
Bone scintigraphy is used to assess degree of bone involvement (considered
sensitive, but not specific).
what is used to assess degree of bone involvement in prostate cancer bone metastasis
bone scintigraphy
For clinically-localized prostate cancer, choice of therapy requires the consideration of
- presence of symptoms
- probability that the untreated tumor will adversely affect the quality or duration of survival and thus require treatment,
- probability that the tumor can be cured by single-modality therapy.
localized/Organ-confined
disease (T1-T2) prostate cancer treatment
- Radical prostatectomy
- or radiotherapy
- or active surveillance
Radical prostatectomy - what is removed? what approach is used ?
- Removal of prostate, seminal vesicles +/- LNs
- laparoscopic or open surgery (perineal or retropubic).
indications of radical prostectomy
- age < 70,
- good general condition,
- no capsular invasion
- PSA < 25 ng/mL
- negative bone scan and CXR
side effects of prostatectomy
- sexual dysfunction,
- incontinence
- anastomosis stricture
- rectal injury (due to damage of neurovascular bundles)
after radical prostatectomy 6-weeks post-operatively what happens to PSA levels
PSA should drop to undetectable levels.
If PSA remains or becomes detectable after radical prostatectomy, the patient is
considered to have persistent disease.
Radiotherapy in T1-T2 prostate cancer
- External-beam radiation therapy
- Brachy-therapy (direct implantation of radioactive seeds into the prostate)
Active surveillance in T1-T2 prostate cancer
- Regular follow-ups with cancer re-staging instead of treatment
- Preferred option for most early-stage cancers
Metastatic prostate cancer disease
treatment
- Chemical castration
- or surgical castration (orchiectomy)
**Role of hormonal therapy as adjuvant or neo-adjuvant to radiation therapy or
prostatectomy (at any disease stage) is questionable
Chemical/surgical castration is used in? , which drugs?
- metastatic prostate cancer
- Hormonal therapy (ADT = androgen-deprivation therapy)
*GnRH analogue: leuprolide, goserelin
*GnRH antagonist: degarelix, ganirelix
*Anti-androgens: flutamide, bicalutamide
Hormonal therapy (ADT = androgen-deprivation therapy)
used in metastatic prostate c
*GnRH analogue: leuprolide, goserelin
*GnRH antagonist: degarelix, ganirelix
*Anti-androgens: flutamide, bicalutamide
Androgen depletion syndrome
clinical manifestation
occurs in metastatic prostate c
* hot flushes,
* weakness, fatigue,
* loss of libido
* impotence
* anemia,
* depression
* CV risk increases
* decreased BMD
* metabolic syndrome (waist circumference, HTN, TG, HDL, high blood sugar)
Castration-resistant
prostate cancer (CRPC) is defined as
Defined as disease that progresses despite androgen suppression (by medical or surgical therapies)
where the measured levels of testesterone are ≤ 50 ng/ml
Castration-resistant
prostate cancer (CRPC) treatment
- Estramustine phosphate (EMP) : dual estrogen agent (antiandrogen effect) and chemotherapy agent (antimicrotubular effect); also known as estracyst treatment
- Docetaxel
- Newer antiandrogens (eg. enzalutamide)
newer antiandrogen used in castration resistant prostate cancer
- Newer antiandrogens (eg. enzalutamide)
Supportive care in prostate cancer
- Anemia: Fe, EPO, transfusions
- Bone metastasis: Ca2+, vitD, Bisphosphonate, denosumab
- Spinal cord compression: corticosteroids
- Hydronephrosis: percutaneous nephrostomy
- Total retention: palliative TURP to relief obstruction
- Pain-management: local radiation therapy, analgesics
Total retention in prostate cancer how to treat
palliative TURP to relief obstruction
Spinal cord compression treatment in prostate cancer
corticosteroids
bone metastasis treatment in prostate c
Ca2+,
vitD,
Bisphosphonate, denosumab
