Prostate Carcinoma

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Etiology 3 Epidemiology 4 Pathology 5 Genetics 6 Clinical-manifestations 7 Laboratory 8 Radiology 9 Complications 10 Differential-diagnosis 11 Management 12 More General Terms 13 Additional Terms 14 Internet Database 15 References

More Specific Terms

• prostate adenocarcinoma

Etiology

• cause unknown
• risk factors:

• family history
• age > 50
• black race
• vasectomy (evidence/association weak)
• dietary fat
• occupational exposure to cadmium or rubber
• colon cancer
• obesity [18]
• low levels of vitamin D [18]
• excessive use of multivitamin [31]

• folic acid 1 mg QD associated with 3-fold risk [45]
• vitamin E 400 IU QD increase risk 17% [66]

• circumcision lowers risk (HR=0.85) [69]

• generally slow growing, androgen sensitive

• serum levels of testosterone & estradiol NOT related to risk of prostate cancer in healthy men [39]

• virtually all are adenocarcinoma

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 [42]
• incidence 240,000 cases/year
• 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 [40]
• prevalence is 7% with serum PSA < 0.5 ug/L, 27% with serum PSA 3.1-4.9 ug/L [15]
• 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 [6]

• fish consumption ( omega-3 fatty acids?) may reduce risk [5]

• increased serum DHA associated with high-grade prostate cancer [58]

• red wine* consumption may reduce risk [17] *(see prophylaxis)
• incidence increases in populations further from the equator ( sunlight, vitamin D may play role)

Pathology

• arises 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
• microvessel density associated with mortality (HR=3.0, highest vs lowest quartile) [46]

• * bone is most frequent site of distant metastases

Genetics

• 5% of cases may be familial

• susceptibility to prostate cancer

• defects in RNASEL (type 1)
• defects in ELAC2

• defects in AR may play a role in metastatic prostate cancer; the mutated receptor stimulates prostate growth & metastases development despite of androgen ablation
• defects in bcl-2 (HR=1.6) & p53 (HR=1.5) associated with increased risk of mortality [46]
• 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 [10]

• 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 [36]
• other implicated genes REPS2, PBOV1, STEAP1, GPR148, UBIAD1, AGK, CSAG2, TAK1L, FAM48A, BCL9L, AFAP1, SRD5A3, XRRA1, GREB1, CTNNB1, CCNDBP1, DERPC, PEG10, NOX5, PCOTH, SLC5A8, MXI1, PTEN, AR, SLC43A1, OR51E1, OR51E2, EPHB2, CHEK2, PKN3, FOLH1, CDKN3, LGALS8, BIRC5, IRX5, PSCA, USP7, TNK2, NKX3-1

Clinical-manifestations

• generally asymptomatic
• urinary obstruction

• may be rapid in onset
• urgency, frequency, hesitancy, nocturia
• more commonly associated with BPH

• regional symptoms:

• hematuria
• lower extremity edema

• systemic symptoms:

• back pain secondary to spinal metastases
• weight loss
• weakness
• lymphadenopathy

• digital rectal exam:

• prostate nodule
• induration
• enlargement
• may be 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

• prostatic acid phosphatase ( PAP)

• evaluation of non-localized disease

• liver function tests ( liver metastases)
• transrectal biopsy or fine-needle aspiration
• PCR/ southern blot
• Microarray technology has identified 2 proteins which may play an important role; hepsin & pim-1 kinase [7] <research>
• other markers: PI16 <research>
• autoantibodies: KIAA1524 <research>

Radiology

• bone scans

• indications:
• PSA > 10 ng/mL
• bone pain
• NOT routinely indicated for follow-up [2]

• transrectal ultrasound

• evaluation of hypoechoic areas of prostate for biopsy
• ultrasound guided biopsy

• dexa-scan for bone mineral density with androgen deprivation therapy

Complications

• disseminated intravascular coagulation
• bony metastases, osteoblastic rather than osteolytic [37]
• metastases to brain
  
• disease interaction(s) of cancer with Alzheimer's disease

Differential-diagnosis

• prostatitis
• benign prostatic hypertrophy ( BPH)

Management

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

• observation [52,55]
• surgery

• transurethral resection/ incision of the prostate ( TURP, TUIP) <also see prostatectomy>
• urethral stents
• radical prostatectomy

• slightly better outcomes than observation [22]

• reserved for patients with life-expectancy > 10 years
• 15-year survival in early prostate cancer favor prostatectomy over watchful waiting (15 vs 21% mortality) [60]

• radiation therapy / brachytherapy

• poor surgical candidates
• high-grade malignancy
• best results when used in combination with androgen antagonist [47] starting 2 months prior to radiation, 4 months duration [64]
• intensity-modulated radiation therapy provides some benefits versus conformal radiation therapy or proton therapy [71]

• cryotherapy/ cryoablation: new therapy, long term result? [14, 14b-f]
• observation & radiation result in similar long-term survival
• see Prostate Cancer Outcomes study
• surgery &/or radiation may benefit elderly (> 75) [28]
• radical prostatectomy & radiation equivalent outcomes [2]
• dutasteride lowers risk for disease progression [67]
• specialist visits strongly influence prostate cancer treatment choices [56]

• specialists tend to recommend treatment that they deliver
• men seen by primary care providers were more likely to be observed rather than treated [56]

• overscreening & overtreatment of elderly men common [61]

• regional involvement or metastatic disease (T3*, C*, D)

• hormonal therapy

• bilateral orchiectomy
• pharmacologic agents

• LHRH agonist with or without androgen antagonist [2]

• starting LHRH agonist can cause a tumor flare & clinical worsening
• flare can be attenuated with androgen antagonist

• GnRH analogues ( LHRH agonist)

• use in conjunction with androgen antagonists begun several days earlier#
• goserelin ( Zoladex)
• leuprolide ( Lupron)
• buserelin

• androgen antagonists

• bicalutamide ( Casodex)
• flutamide ( Eulexin)
• nilutamide

• diethylstilbestrol
• agents that suppress adrenal androgen production [37]

• ketoconazole
• aminiglutethimide

• as effective as bilateral orchiectomy in reducing serum testosteron, but NOT curative
• duration of therapy (in combination with radiation): 3 years better than 6 months [47]
• increases 5 year risk of cardiovascular death (5.5% vs 2.0%) [35]
• increased mortality in men with heart failure due to CAD or history of MI [50]
• bisphosphonates
• may reduce osteoporosis, fractures
• do not increase survival, slow disease progression, improve quality of life, diminish pain [2]

• surgery

• radical prostatectomy plus combined ( GnRH agonist plus antiandrogen) therapy for 2 years [63]
• robotic surgery associated with a higher rate of urinary incontinence than radical prostatectomy [68]

• radiation therapy [25]

• preferred modality for stage T3 (C)
• impotence is less frequent than with surgery
• men with positive surgical margins benefit most [34,49]
• a 6 month course of androgen-deprivation therapy prior to radiation therapy improves mortality by 50% in men with locally-advanced prostate cancer [57]

• high-intensity focal ultrasound [70]
• chemotherapy (androgen-independent metastatic disease)

• 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) [29]
• docetaxel + prednisone every 3 weeks (androgen-independent prostate cancer) [38]
• no benefit of chemotherapy in addition to androgen deprivation prior to androgen-independence [44]
• inhibition of CYP17 with abiraterone acetate +/- dexamethasone may be useful in treatment of castration-resistant prostate cancer [51,53]

• Astenar in phase 3 clinical trials
• GM-CSF secreting allogeneic irradiated prostate cancer cell lines may be of some benefit [33]
• sipuleucel-T ( Provenge) immunotherapy for metastatic disease

• follow-up

• PSA & digital rectal exam q3-6 months
• bone scan yearly (only if specifically indicated by clinical signs & symptoms) [2]
• evaluation for complications of prostatectomy or radiation
• bone mineral density with androgen deprivation therapy

• bisphosphonate therapy for osteoporosis [54]

• prognosis:

• factors associated with progression of disease include:

• younger age
• higher clinical stage
• higher Gleason score
• higher serum PSA at diagnosis
• smoking increases disease-specific mortality [62]

• average duration of survival in patients with metastatic disease is 2-3 years
• prognosis better for those with PSA < 4 ng/mL & even better for those with PSA < 0.2 ng/mL after androgen deprivation therapy [24]
• 20 year mortality for untreated local disease is about 15% [16]
• older patients with localized disease unlikely to die as a result of prostate cancer; mortality is dependent on comorbidities [59]
• erectile dysfunction is common 2 years after treatment
• 37% of all patients & 48% of those with functional erections before treatment [65]

• screening: see screening for prostate cancer
• prophylaxis

• finasteride may decrease risk of prostate cancer without paraxodical excess of high-grade tumors [41]

• see finasteride prophylaxis study & ref [41]
• number needed to treat: 71 men for up to 7 years to prevent one case of prostate cancer [48]

• lycopenes in tomatoes may have some benefit
• pumpkin seeds have been claimed to have benefit
• foods rich in boron may provide protective effect [12]
• increased frequency of ejaculation reduces risk [13]
• resveratrol in red wine may reduce risk [17]
• green tea may be prophylactic [19]
• NSAIDS may reduce risk [20]
• statin may reduce risk of metastatic, but not localized prostate cancer [21]
• isothiocyanates & curcumin may have some benefit
• cruciferous vegetables & to a lesser extent spinach may diminish risk of extra- prostatic disease [32]
• vitamin E 400 IU/day, vitamin C 500 mg/day, or selenium 200 ug/day of no benefit [43]
  

• * aggressive surgery is sometimes used for stage T3 (C) disease
• # may be no benefit to combined GnRH analogue/ androgen antagonist therapy [6]

More General Terms

• prostatic neoplasm
• carcinoma
• urogenital malignancy (urogenital cancer)
• chronic urogenital disease

Additional Terms

• benign prostatic hyperplasia (BPH)
• Gleason scoring system for prostate cancer
• PCR/southern blot for prostate cancer
• prostate
• Prostate Cancer Outcomes study
• screening for prostate cancer
• staging of prostate cancer

Internet Database

OMIM: 176807
OMIM: 601518
OMIM: 600623
OMIM: 603688

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    - Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. ngc-guideline: [106]
    - The use of bisphosphonates in men with hormone-refractory prostate cancer. (Practice Guidelines Initiative) ngc-guideline: [107]
    - Prostate cancer. (Intracorp) ngc-guideline: [108]
    - Prostate cancer. (Association of Comprehensive Cancer Centres) ngc-guideline: [109]
    - Post-treatment follow-up of prostate cancer. American College of Radiology ngc-guideline: [110]
    - Non-hormonal systemic therapy in men with metastatic hormone-refractory prostate cancer: a clinical practice guideline. (Program in Evidence-based Care) ngc-guideline: [111]
    - Pretreatment staging prostate cancer American College of Radiology ngc-guideline: [112]
    - Locally advanced (high-risk) prostate cancer. American College of Radiology ngc-guideline: [113]
    - Permanent source brachytherapy for prostate cancer. American College of Radiology ngc-guideline: [114]
    - External beam radiation therapy treatment planning for clinically localized prostate cancer. (American College of Radiology) ngc-guideline: [115]
    - ACR Appropriateness Criteria definitive external beam irradiation in stage T1 and T2 prostate cancer. ngc-guideline: [116]
    - Postradical prostatectomy irradiation in prostate cancer. (American College of Radiology) ngc-guideline: [117]
    - Practice guideline for transperineal permanent brachytherapy of prostate cancer. (American College of Radiology) ngc-guideline: [118]
    - Guideline for the management of clinically localized prostate cancer: 2007 update. American Urological Association Education and Research, Inc. ngc-guideline: [119]
    - Adjuvant radiotherapy following radical prostatectomy for pathologic T3 or margin-positive prostate cancer: guideline recommendations. Program in Evidence-based Care ngc-guideline: [120]
    - Best practice policy statement on cryosurgery for the treatment of localized prostate cancer. American Urological Association Education and Research, Inc. ngc-guideline: [121]
    - Prostate cancer. Diagnosis and treatment. National Collaborating Centre for Cancer ngc-guideline: [122]
    - Guideline for optimization of surgical pathological quality performance for radical prostatectomy in prostate cancer management: surgical and pathological guidelines. Program in Evidence-based Care ngc-guideline: [123]
    - Use of 5-alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology- American Urological Association 2008 Clinical Practice Guideline. ngc-guideline: [124]
    - Clinical practice guideline for prostate cancer treatment. Aragon Institute of Health Sciences ngc-guideline: [125]

prostate carcinoma (prostate cancer)