prostate cancer

Etiology

• cause unknown
• risk factors:
  • family history, prostate cancer in a 1st degree relative
  • age > 50
  • black race
  • vasectomy (no association)
    • no associations between vasectomy & incident high-grade, advanced, or fatal prostate cancer
  • dietary fat
  • cow's milk consumption, especially aggressive or fatal forms
  • occupational exposure to cadmium or rubber
  • colon cancer
  • obesity in black men
  • low levels of vitamin D
  • excessive use of multivitamin
    • folic acid 1 mg QD associated with 3-fold risk
    • vitamin E 400 IU QD increases risk 17%
  • omega-3 fatty acids increase risk (RR-1.4-1.7)
  • bisphenol A (BPA) exposure increases risk
  • circumcision lowers risk (HR=0.85)
  • frequent ejaculation may diminish risk
• generally slow growing, androgen sensitive
  • serum levels of testosterone & estradiol NOT related to risk of prostate cancer in healthy men
• 5-alpha-reductase inhibitors not a risk for high-grade prostate cancer.
• finasteride reduces risk of prostate cancer, but not cancer mortality

Epidemiology

• most common malignancy in men, excluding skin cancers
• one in six men will develop prostate cancer; one in 35 men will die of it
• incidence 240,000 cases/year
  • increased incidence of metastatic prostate cancer in the United States (2004-2013)
    • 92% increase in men 55-69 years of age
    • for men 45-74, 17 cases of metastatic prostate cancer/100,000
    • for men > 75, 89 cases of metastatic prostate cancer/100,000
• 2nd most common cause of cancer mortality in men 40,000/year
• 23% of men > 50, 35% of men > 60, 46% of men > 70 years with autopsy-confirmed prostate cancer
• prevalence 45%-59% for men in > 60 years, increasing with age
• prevalence is 7% with serum PSA < 0.5 ug/L, 27% with serum PSA 3.1-4.9 ug/L
• mean age at diagnosis: 72 years
• 10 year disease-specific survival for localized disease: 80-90%
• racial predilection: blacks > whites > Japanese
  • uncommon in Asian countries
• fish consumption (omega-3 fatty acids?) may reduce risk
  • increased serum DHA associated with high-grade prostate cancer
• red wine* consumption may reduce risk *(see prophylaxis)
• incidence increases in populations further from the equator (sunlight, vitamin D may play role)
• diagnosis of early stage prostate cancer has declined since USPSTF recommendation against screening for prostate cancer
• transgender women retain prostate after gender-affirmation surgery & remain at risk of prostate cancer, regardless of estrogen use

Pathology

• most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts (95%)
• other rare histopathologic types of prostate cancer include:
  • small cell carcinoma
  • mucinous carcinoma
  • prostatic ductal carcinoma
  • transitional cell carcinoma
  • squamous cell carcinoma
  • basal cell carcinoma
  • adenoid cystic carcinoma
  • signet-ring cell carcinoma
  • neuroendocrine carcinoma
• most prostate cancers arise primarily from the peripheral zone of the prostate
• surgical pathology
  • 20-30% with capsular invasion or seminal vesicle involvement
  • 40% of cases with positive margins
• Gleason scoring system
• metastases
  • lymph nodes (68%)
  • liver (36%)
  • lung (49%)
  • bone* (67%)
  • brain (2%)
  • skin (3%)
  • adrenal (17%)
  • kidney (11%)
• histone-arginine methyltransferase CARM1 overexpressed
• increased levels of IL11RA
• PSMA is overexpressed in prostate cancer
  • PSMA negative in tumor cells (stains vessels)
• microvessel density associated with mortality (HR=3.0, highest vs lowest quartile)
• immunocytochemistry:
  • PSA positive (prostate origin)
  • NJX3.1 positive (prostate origin)
  • AMACR positive (prostate origin)
  • CK8/18 positive (carcinoma)
  • EpCAM (MOC31) positive (carcinoma)
  • CD45 negative (lymphoma, hematopoietic neoplasm)
  • pancytokeratin negative
  • CD7 & CD20 negative
  • TTF1 & napsin negative (lung origin)
  • P63 & HMWCK negative (squamous differentiation)
  • synaptophysin & chromogranin negative (neuroendocrine differentiation)
  • D2140, c-kit, & CD30 negative (germ cell tumor)
  • Sall4 negative (germ cell tumor)
  • mucicarmine negative (intracelluar mucin)
  • 0HMB45, MART, S100 & Sox10 negative (melanoma)
  • Pax8 negative (renal)
  • HepAr1 & Arginase negative (hepatocellular origin)

* bone is most frequent site of distant metastases

Genetics

• 5% of cases may be familial
  • 12% of men with metastatic prostate cancer have at least one germline mutation in a gene involved in DNA-repair
    • mutations identified in 16 different genes, including BRCA2 (5.3%), ATM (1.6%), CHEK2 (1.9%), BRCA1 (0.9%), RAD51D (0.4%), & PALB2 (0.4%)
  • susceptibility to prostate cancer
    • defects in RNASEL (type 1)
    • defects in ELAC2
    • defects in MSMB (type 13)
• metastatic castration-resistant prostate cancer
  • defects in androgen receptor (AR)
    • the mutated receptor stimulates prostate growth & metastases despite androgen ablation
  • TP53
  • less frequently BRAF, BRCA2, & BRCA1
• defects in bcl-2 (HR=1.6) & p53 (HR=1.5) associated with increased risk of mortality
• associated with defects in KLF6
• some genes found to be hypermethylated include:
  • cyclin dependent kinase inhibitor 2A (CDKN2A)
  • glutathione S transferase protein 1 (GSTP1)
  • estrogen receptor (ER)
  • CH1, INTS6, CD44, endothelin receptor (EDNRB)
• EZH2 gene
  • increased expression in BPH & prostate cancer
  • expression better clinical predictor than Gleason score
• single nucleotide polymorphisms in 5 chromosomal regions, 3 at 8q24, 1 at 17q12, 1 at 17q24.3 confer higher risk
• androgen receptor splice variant 7 in circulating tumor cells associated with resistance to enzalutamide & abiraterone
• loss of NCOR2 expression may accelerate resistance to androgen deprivation therapy in prostate cancer
• other implicated genes
  • STAT3, NKX3.1, KLK3
  • REPS2, PBOV1, STEAP1, GPR148, UBIAD1, AGK, CSAG2, TAK1L, FAM48A, BCL9L, AFAP1, SRD5A3, XRRA1, GREB1, CTNNB1, CCNDBP1, DERPC, PEG10, NOX5, PCOTH, SLC5A8, MXI1, SLC43A1, OR51E1, OR51E2, EPHB2, PKN3, FOLH1, CDKN3, LGALS8, ECAC2, BIRC5, IRX5, PSCA, USP7, TNK2,, COL18A1, CD164, TBC1D3

Clinical manifestations

• generally asymptomatic
• urinary obstruction
  • may be rapid in onset
  • urgency, frequency, hesitancy, nocturia
  • more commonly associated with BPH
• regional signs/symptoms:
  • hematuria
  • lower extremity edema
• systemic signs/symptoms:
  • bone pain or back pain secondary to spinal metastases
  • weight loss
  • weakness
  • lymphadenopathy
• digital rectal exam:
  • prostate nodule
  • induration
  • enlargement
  • may be normal
  • abnormal digital rectal examination should prompt referral to urology for transrectal prostate biopsy even if serum PSA is normal
• unusual presentations
  • hydronephrosis
  • adenocarcinoma, primary unknown

Laboratory

• prostate-specific antigen (PSA)
  • abnormal is > 4 ng/mL
  • may be abnormal in benign prostatic hypertrophy (BPH) & prostatitis
  • normal in 40% of patients with prostate cancer
  • > 10 ng/mL suggests prostate cancer vs prostatitis
  • any increase in serum PSA after prostatectomy indicates active prostate cancer
  • a progressive increase in serum PSA after radiation therapy is needed for diagnosis of recurrence
  • urinary obstruction increases serum PSA regardless of cause
• prostatic acid phosphatase (PAP)
  • evaluation of non-localized disease
• liver function tests (liver metastases)
• transrectal biopsy or fine-needle aspiration (FNA)
• prostate cancer pathology panel
• Multigene Panels
  • microarray technology has identified 2 proteins which may play an important role; hepsin & pim-1 kinase <research>
  • prostate cancer genotyping
  • BRCA1/BRCA2 genotyping
    • high risk disease, positive lymph nodes, or metastatic disease
  • Oncotype Dx for prostate cancer
  • prostate cancer promoter methylation profiling
  • 18-gene prostate cancer urine panel may reduce additional testing for high-grade cancer in patients undergoing PSA screening
• other markers:
  • PI16 <research>
  • prostate cancer antigen 3 in feces
  • P504S Ag in tissue
  • HMW cytokeratin Ag in tissue
• pathology reports
  • other nodules > 10 mm in prostate cancer
  • other nodule quadrant in prostate cancer
  • other nodule plane in prostate cancer
• autoantibodies: KIAA1524 <research>
• see ARUP consult

Diagnostic procedures

• transrectal ultrasound
  • evaluation of hypoechoic areas of prostate for biopsy
  • not routinely indicated for diagnosis; biopsy still needed
  • ultrasound guided biopsy
  • Gleason score determined from prostate biopsy

Radiology

• in low risk prostate cancer, imaging studies not necessary*
• bone scan
  • indications:
    • serum PSA >= 10 ng/mL; Gleason score >= 8; stage T3 or T4*
    • bone pain & diagnosis of prostate cancer has been established
    • NOT routinely indicated for follow-up
• magnetic resonance imaging (MRI)
  • multiparametric MRI with greater sensitivity than transrectal ultrasound guided biopsy (93% vs 48%) but lower specificity (41% vs. 96%)
  • MRI prior to biopsy could avoid 27-30% of biopsies
    • integrating MRI in prostate cancer screening can reduce unnecessary biopsies & overdiagnosis of insignificant prostate cancer
  • in men with elevated serum PSA, MRI in combination with prostate biopsy diagnosed more cancers than either alone
• dexa-scan for bone mineral density with androgen deprivation therapy
• PET-CT scan
  • PSMA is overexpressed on prostate cancer cells
  • PET-CT using PSMA allows tumor-specific imaging of the entire body

* imaging studies to assess regional lymph node involvement or metastases indicated only for men at high risk

Complications

• disseminated intravascular coagulation
• bony metastases, osteoblastic rather than osteolytic
  • external beam radiotherapy or radium-223
• complications of androgen deprivation therapy (osteoporotic fracture)
• iron-deficiency anemia due to radiation proctitis from radiation therapy
• metastases to brain
• obesity associated with increased all-cause mortality, cardiovascular mortality, & possibly prostate cancer-specific mortality
• weight gain after prostate cancer diagnosis associated with increased prostate cancer-specific mortality
• 78% of men with metastatic prostate cancer die from it
• treatment-related complications:
  • at 12 years, risk of urinary or sexual complications is 7-fold greater after prostatectomy & nearly 3-fold greater after radiotherapy vs men without prostate cancer

• disease interaction(s) of prostate cancer with Covid-19

Differential diagnosis

• prostatitis
• benign prostatic hypertrophy (BPH)

Management

localized disease (stages T1, T2, A2, B)

• observation (watchful waiting) vs active surveillance
  • low risk & life expectancy < 10 years
  • low risk & life expectancy > 10 years
    • active surveillance with serum PSA every 3-6 months, digital rectal exam yearly & repeat prostate biopsy at 6-12 months & every 2-5 years thereafter
    • compliance with active surveillance is low
      • 31% guideline-concordant
      • 31% concordant for PSA testing but not biopsy
      • 16% concordant for biopsy but not PSA testing
      • 22% discordant for both PSA testing & biopsy
    • effect of compliance on clinical outcomes is unclear
    • anxiety with active surveillance in ~1/3 of men after 1 year
  • outcomes of active surveillance as favorable in men older & older than 60 years of age
    • active surveillance for low-risk prostate cancer appears similarly safe in Black & white men
    • survival is no different in men with low-risk localized prostate cancer regardless of treatment (prostatectomy, radiation or active surveillance)
    • 1/2 of patients managed with active surveillance maintained low-grade classification after 7 years, with prostate cancer mortality of 0.1%
  • Gleason score of 7 (3+4) or less
  • serum PSA < 10 ng/mL
    • free PSA plays no role in active surveillance: prostate biopsy per protocol
  • if risk of mortality from prostate cancer is < risk of mortality from other causes, observation would seem appropriate
  • patients in multidisciplinary clinics are more likely to opt for active surveillance
  • employ shared decision making
  • low-risk prostate cancer has a favorable prognosis without treatment
  • high vegetable diet of no benefit for slowing progression in low-risk prostate cancer
  • Mediterranean diet may help slow or prevent progression of prostate cancer in men on active surveillance
• surgery for localized disease
  • transurethral resection/incision of the prostate (TURP, TUIP) <also see prostatectomy>
  • urethral stents
  • radical prostatectomy
    • slightly better outcomes than observation
    • reduces bone metastases but not all cause or prostate cancer-specific mortality
  • reserved for patients with life-expectancy > 10 years
  • survival in early prostate cancer favors prostatectomy over watchful waiting
    • diminishes risk of death from prostate cancer
      • 15% vs 21% mortality after 15 years
      • 18% vs 29% after 18 years
  • surgery is not associated with diminished mortality vs observation in patients with localized prostate cancer
    • surgery is associated with more adverse effects, but less treatment for disease progression, mostly asymptomatic, local, or biochemical progression
  • benefit of prostatectomy vs active surveillance highly dependent on baseline risk, <A3037>NNT</A3037>=8 for localized prostate cancer
  • radical prostatectomy holds a cancer-specific mortality advantage over external beam radiation therapy in high-risk localized prostate cancer
  • prostatectomy associated with urinary incontinence & erectile dysfunction
• radiation therapy / brachytherapy
  • poor surgical candidates
  • high-grade malignancy
  • best results when used in combination with androgen antagonist starting 2 months prior to radiation, 4 months duration
    • 6-12 monnths of androgen deprivation therapy after radiation
  • hormonal therapy not recommended for low-risk patients (localized disease with Gleason score < 8)
  • intensity-modulated radiation therapy provides some benefits versus conformal radiation therapy or proton therapy
  • proton beam radiotherapy not recommended
  • radiation therapy associated with short-term risk for enteritis radiation proctitis & cystitis & long-term risk of erectile dysfunction
  • low-dose brachytherapy associated with increase risk of secondary pelvic cancer (bladder cancer, rectal cancer) 6.4% at 15 years 7 9.8% at 20 years vs 3.2% & 4.2% after prostatectomy
    • overall risk of any secondary cancer not higher for brachytherapy
• stereotactic ablative radiotherapy may benefit limited metastatic (oligometastatic) prostate cancer
• focal ablative therapy may benefit elderly who wish to avoid complications from radical intervention
  • high-intensity focal ultrasound
  • cryotherapy/cryoablation: new therapy, long term result?
  • 5-year failure-free survival higher with radical intervention ((96% vs 82%) but 5-year survival for focal ablative therapy is 96%
• surgery &/or radiation may benefit elderly (> 75)
• see prostate cancer outcomes
• dutasteride lowers risk for disease progression
• specialist visits strongly influence prostate cancer treatment choices
  • specialists tend to recommend treatment that they deliver
  • men seen by primary care providers were more likely to be observed rather than treated
• men age >= 60 years with 3 or more comorbidities may not benefit from treatment
• individualize therapy for older men
• androgen deprivation therapy for stage T1-T2 prostate cancer does not confer 15 year survival benefit
• androgen deprivation therapy for localized prostate cancer in men with multiple comorbidities is associated with increased mortality
• apalutamide (Erleada) FDA-approved for non-metastatic, castration-resistant prostate cancer
• enzalutamide & darolutamide also FDA-approved for non-metastatic, castration-resistant prostate cancer
• 13% of men surveyed experienced treatment-related regret
  • 16% of men who opted for prostectomy regretted their decision
  • 11% of men who opted for radiotherapy regretted their decision
  • 7% who chose active surveillance regretted their decision

<newline>=== regional involvement or metastatic disease ===

• hormonal therapy (androgen deprivation therapy)
  • bilateral orchiectomy (cost-effective, rapidly-acting)
  • intermittent vs continuous androgen deprivation
    • continuous androgen deprivation may improve outcomes in patients with metatatic disease relative to intermittent androgen deprivation
    • intermittent androgen deprivation of no benefit
  • pharmacologic agents
    • LHRH agonist with or without androgen antagonist
      • starting LHRH agonist can cause a tumor flare & clinical worsening
      • flare can be attenuated with androgen antagonist
      • first line therapy
    • GnRH analogues (LHRH agonist)
      • use in conjunction with androgen antagonists begun several days earlier#
      • goserelin (Zoladex)
      • leuprolide (Lupron)
      • buserelin
      • histrelin
      • triptorelin
    • defarelix (GnRH antagonist)
    • abiraterone actetate in combination with prednisone or prednisolone & androgen deprivation therapy
      • abiraterone actetate blocks androgen synthesis
    • diethylstilbestrol
    • agents that suppress adrenal androgen production
      • ketoconazole
      • aminiglutethimide
  • as effective as bilateral orchiectomy in reducing serum testosterone, but NOT curative
  • duration of therapy (in combination with radiation): 3 years better than 6 months
  • increases 5 year risk of cardiovascular death (5.5% vs 2.0%)
  • increased mortality in men with heart failure due to CAD or history of MI
  • docetaxel with androgen-deprivation therapy results in longer survival in men with metastatic prostate cancer
    • LHRH agonist with androgen antagonist (androgen-deprivation therapy) plus docetaxel ([2]
  • supplemental calcium & vitamin D
  • bisphosphonates
    • may reduce osteoporosis, fractures
    • do not increase survival, slow disease progression, improve quality of life, diminish pain
  • denosumab may be more effective than zoledronate in preventing complications from bone metastases
  • androgen deprivation therapy is associated with
    • osteoporosis
    • possibile increased cardiovascular risk
    • increased risk for venous thromboembolism
• androgen antagonists may be used in combination with androgen deprivation therapy
  • bicalutamide (Casodex)
  • flutamide (Eulexin)
  • nilutamide
  • apalutamide (Erleada)
  • enzalutamide for androgen deprivation therapy failure (see Prevail trial, NICE)
• surgery
  • radical prostatectomy Plus combined (GnRH agonist plus antiandrogen) therapy for 2 years
  • robotic surgery associated with a higher rate of urinary incontinence than radical prostatectomy
  • radical prostatectomy no better than observation for localized prostate cancer in men >= 65 years of age
  • relative contraindications for radical prostatectomy
    • extension of malignancy outside the prostate
    • serum PSA > 20 ng/mL
    • Gleason score >= 8
• radiation therapy
  • preferred modality for stage T3 (C)
  • impotence is less frequent than with surgery
  • men with positive surgical margins benefit most
  • a 6 month course of androgen-deprivation therapy prior to radiation therapy improves mortality by 50% in men with locally-advanced prostate cancer **** <- (MKSAP18)
  • does not improve survival or distant metastases after radical prostatectomy in patients with T3 disease or positive surgical margins
  • early salvage radiotherapy after prostatectomy for high-risk cancer
  • external beam radiotherapy for localized painful bone metastasis
    • not needed in the absence of neurologic deficits or pain
  • IV radium-223 for multiple painful bone metastases (see bone metastases)
    • bone-targeted alpha-emitting radiation may improve survival in metastatic castrate-resistant prostate cancer
    • beta-emitting radiation not as helpful
    • intensification with higher dose or prolonged radium-223 of no benefit & is associated with increased harm
  • radiation therapy for prostate cancer results in small increase in risk for bladder cancer & colorectal cancer
  • increased short-term risk for cystitis & enteritis & long-term risk for erectile dysfunction
• high-intensity focal ultrasound
• surgery vs radiation vs observation for localized prostate cancer (2-3 year outcomes)
  • androgen deprivation therapy + external beam radiotherapy + brachytherapy or radical prostatectomy for Gleason score 9-10
  • radical prostatectomy & radiation therapy (external beam or brachytherapy) associated with with worse sexual dysfunction relative to observation
  • radical prostatectomy associated with more sexual dysfunction & urinary incontinence than observation, but less dysuria
  • external beam radiotherapy associated with bowel symptoms & with short-term worsening of urinary obstruction & irritation
  • ultra-high single-dose radiotherapy is an alternative to curative extreme hypofractionated stereotactic body radiotherapy in organ-confined prostate cancer
  • brachytherapy associated with short-term worsening of urinary obstruction & irritation
  • 10 year outcomes for brachytherapy compares favorably to surgery & external beam radiation therapy
• chemotherapy (androgen-independent metastatic disease)
  • continue androgen-deprivation therapy indefinitely
  • docetaxel 36 mg/m2 IV weekly for 4 weeks, with or without calcitriol 45 mg PO 1 day prior to docetaxel (androgen-independent prostate cancer)
  • docetaxel + prednisone every 3 weeks (androgen-independent prostate cancer)
  • no benefit from addition of carboplatin to docetaxel
    • combination results in more toxicity
  • cabazitaxel + prednisone
  • no benefit of chemotherapy in addition to androgen deprivation prior to androgen-independence
  • inhibition of CYP17 with abiraterone acetate +/- dexamethasone or predisone may be useful in treatment of castration-resistant prostate cancer
  • cabozantinib shows promise in clinical trial
  • enzalutamide (androgen receptor antagonist) for metastatic castration-sensitive & castration-resistant prostate cancer
    • prior to chemotherapy may be useful (Pevail trial)
    • reduces risk of radiographic progression or death
  • apalutamide (Erleada) or abiraterone may be also be used with androgen-deprivation therapy rather than enzalutamide
    • increased risk of cardiovascular events when androgen receptor antagonist used in combination with conventional androgen deprivation therapy
  • PARP inhibitor may be of benefit
    • FDA has approved 2 PARP inhibitors for androgen-independent metastatic prostate cancer (rucaparib & olaparib)
    • olaparib may benefit 1/3 of patients with metastatic androgen-insensitive prostate cancer (median overall survival of 10.1 months) [128, 186]
    • benefit for patients with BRCA1, BRCA2, or ATM aberrations
  • abiraterone + glucocorticoid after failed androgen deprivation therapy, before chemotherapy (NICE)
• Astenar in phase 3 clinical trials
• GM-CSF secreting allogeneic irradiated prostate cancer cell lines may be of some benefit
• sipuleucel-T (Provenge) immunotherapy for metastatic disease
• 5-alpha reductase inhibitors may reduce prostate cancer mortality in men with prostate cancer; not so (MKSAP19)

follow-up including relapse

• serum PSA & digital rectal exam every 6-12 months
  • serum PSA every 6 months for 1st 5 years, then annually
• bone scan yearly (only if specifically indicated by clinical signs & symptoms)
• evaluation for complications of prostatectomy or radiation
  • patients with radiation treatment may be at increased risk for bladder cancer & colorectal cancer & may need to screening as high-risk patients
• androgen deprivation therapy increases risks for
  • osteoporosis
    • bone mineral density (DEXA) assessment
    • bisphosphonate therapy for osteoporosis
    • no evidence for routine administration of zoledronate
    • zoledronate & denosumab reduce bone loss & risk of fractures due to androgen deprivation therapy
    • vitamin D & calcium
  • anemia
    • complete blood count annually
• relapse confined to elevated serum PSA without other signs of cancer recurrence
  • androgen deprivation therapy if serum PSA doubling time is < 10 months
  • no harm in delaying androgen deprivation therapy until other signs or symptoms of local recurrence or metastases
  • if already on androgen deprivation therapy, add androgen receptor blocker (apalutamide or enzalutamide)
• assess for erectile dysfunction using validated tools
• manage cardiovascular risk, includin dyslipidemia & hypertension

<newline>=== prognosis ===

• factors associated with progression of disease include:
  • younger age
  • higher clinical stage
  • higher Gleason score
    • 36 month cancer-specific mortality for Gleason score = 6 higher in blacks than non-blacks (0.4% vs 0.22%)
  • higher serum PSA at diagnosis
  • smoking increases disease-specific mortality
• average duration of survival in patients with metastatic disease is 2-3 years
  • 32% of deaths 2-5 years after diagnosis; 9% > 5 years after diagnosis
    • 78% of deaths from prostate cancer, 5.5% from other cancers
    • 17% of deaths from noncancer causes, including cardiovascular diseases, COPD, & cerebrovascular diseases
    • in cases of multiple comorbidities, the time horizon for benefit from additional treatment (chemotherapy) is most useful to patients
  • 50% survival with hormone-sensitive metastatic prostate cancer
    • ~75 months 70-74 years, ~63 months 75-79 years, ~55 months >= 80 years
  • 50% survival with hormone-resistant metastatic prostate cancer
    • ~49 months 70-74 years, ~38 months 75-79 years, ~36 months >= 80 years
• prognosis better for those with PSA < 4 ng/mL & even better for those with PSA < 0.2 ng/mL after androgen deprivation therapy
• survival in localized prostate cancer
  • 99% 10 year survival with or without treatment
  • 20 year mortality for untreated local disease is ~ 15%
  • surgery or radiotherapy associated with lower 10-year disease progression (9 vs 23 per 1000 person-years) & metastatic disease (2-3 vs 6 per 1000 person-years)
• older patients with localized disease unlikely to die as a result of prostate cancer; mortality is dependent on comorbidities
• mortality lower with anticoagulant (enoxaparin, warfarin) or antiplatelet agent (aspirin, clopidorel) use
• mortality lower when statin used with androgen deprivation therapy in patients with advanced prostate cancer (27% lower overall mortality & 35% lower prostate cancer-specific mortality)
• erectile dysfunction is common 2 years after treatment
  • 37% of all patients & 48% of those with functional erections before treatment
• a healthy diet reduces risk of disease progression
  • study underway to examine effect of diet on survival in active surveillance patients with prostate cancer
• high-intensity interval training aerobic exercise improved cardiorespiratory fitness & suppressed prostate cancer progression in a phase 2 trial in patients with very low risk to favorable intermediate risk prostate cancer
• quality of life diminished by active treatment of localized disease

prophylaxis & screening

• finasteride & 5-alpha reductase inhibitors in general may decrease risk of prostate cancer without paraxodical excess of high-grade tumors
  • see finasteride prophylaxis study & ref
  • number needed to treat: 71 men for up to 7 years to prevent one case of prostate cancer
  • no increase in life expectancy demonstrated for prophylaxis in men without prostate cancer
• role of diet uncertain
  • lycopenes in tomatoes may have some benefit
  • pumpkin seeds have been claimed to have benefit
  • foods rich in boron may provide protective effect
  • resveratrol in red wine may reduce risk
  • green tea may be prophylactic
  • isothiocyanates & curcumin may have some benefit
  • cruciferous vegetables & to a lesser extent spinach may diminish risk of extra-prostatic disease
  • no significant associations between fruit & vegetable consumption (including cruciferous vegetables) & prostate cancer risk
  • 20 grams of soy protein/day of no benefit in preventing recurrence of locally-advanced prostate cancer
  • vitamin E 400 IU/day, vitamin C 500 mg/day, or selenium 200 ug/day (as selenomethionine) of no benefit
    • men with higher baseline selenium levels show increased risk of prostate cancer with selenium supplementation
    • men with lower baseline selenium show increased risk of prostate cancer with vitamin E supplementation
• NSAIDS may reduce risk
  • low-dose aspirin does not improve survival in men with prostate cancer
• statins
  • may reduce risk of metastatic, but not localized prostate cancer
  • post-diagnosis statin may reduce risk of prostate cancer- specific mortality (RR=0.81) & all-cause mortality (RR=0.85)
  • benefit may be restricted to men on androgen-deprivation therapy
• increased frequency of ejaculation may diminish risk
• smoking cessation may diminish prostate-specific mortality
• screening: see screening for prostate cancer

Investigational

• inhibition of CYP11A1 may improve survival in castration-resistant prostate cancer

* aggressive surgery is sometimes used for stage T3 (C) disease

# may be no benefit to combined GnRH analogue/androgen antagonist therapy

Comparative biology

• lower levels of androgen in mice after castration result in an increase in production of androgen by intestinal bacteria

Notes

• overscreening & overtreatment of elderly men common
• advanced treatment technologies for prostate cancer common among men who are least likely to benefit

More general terms

• prostatic neoplasm
• malignant neoplasm of male genital organ

More specific terms

• androgen-independent prostate cancer; castration resistant prostate cancer (CRPC)
• prostate adenocarcinoma

Additional terms

• benign prostatic hyperplasia (BPH)
• Gleason scoring system for prostate cancer
• prostate
• prostate cancer outcomes
• screening for prostate cancer
• staging of prostate cancer

Patient information

prostate cancer patient information

Database

• OMIM: https://mirror.omim.org/entry/176807
• OMIM: https://mirror.omim.org/entry/601518
• OMIM: https://mirror.omim.org/entry/600623
• OMIM: https://mirror.omim.org/entry/603688
• OMIM: https://mirror.omim.org/entry/611928