Best Dx/Best Rx: Prostate Cancer

From: Subject: Best Dx/Best Rx: Prostate Cancer Date: Wed, 3 Jun 2009 21:43:59 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_022D_01C9E494.66F14370" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_022D_01C9E494.66F14370 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.acpmedicine.com/acp/newrxdx/rxdx/dxrx1209.htm Best Dx/Best Rx: Prostate Cancer

Prostate = Cancer

Philip W. Kantoff, M.D.
Harvard Medical=20 School

Defin= ition/Key=20 Clinical Features
Diffe= rential=20 Diagnosis
Best = Tests
Best = Therapy
Best = References

Definition/Key Clinical=20 Features

The most commonly diagnosed noncutaneous = malignancy in=20 men in the U.S.
The vast majority are adenocarcinomas=20
African Americans have the highest = incidence=20
Tends to spread to lymph nodes and bone =

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Differential = Diagnosis

Benign prostatic hyperplasia=20
Chronic prostatitis

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Best=20 Tests

Screening=20

Goal is to detect organ-confined prostate = cancer, which=20 is potentially curable with definitive local therapy
Optimal screening uses both the = prostate-specific=20 antigen (PSA) test and the digital rectal examination (DRE)
DRE inadequate by itself because most cancers = detectable=20 by DRE are not organ-confined and are therefore incurable=20
PSA testing=20
- Can detect prostate cancer an average of 5.5 = yr before=20 clinical detection=20
- Detection of clinically insignificant = cancers may lead=20 to unnecessary treatment
- Specificity of an elevated PSA is low =
  - Conditions such as benign prostatic = hyperplasia,=20 acute prostatitis, seminal ejaculation, and genitourinary = instrumentation=20 can increase PSA level
- Most men with serum PSA > 10 ng/ml have = prostate=20 cancer, likely to be non-organ-confined=20
- Biopsy in men with serum PSA 4=9610 ng/ml = usually=20 reveals benign prostatic hyperplasia (BPH) rather than prostate=20 cancer=20
- Strategies to distinguish malignancy from = BPH in men=20 with serum PSA 4=9610 ng/ml=20
  - Age-specific serum PSA reference ranges = (< 50 yr:=20 ≤ 2.5 ng/ml; 50=9659 yr: ≤ 3.5 ng/ml; 60=9670 yr: = ≤ 4.5 ng/ml; > 70 yr: ≤=20 6.5 ng/ml)=20
  - Ratio of serum PSA level to volume of = prostate gland=20 (PSA density [PSAD]); in general, patients with cancer have a = higher PSAD=20
  - Determine free PSA level (percentage of = PSA that is=20 unbound to serum proteins); in men with elevated serum PSA, cancer = is more=20 likely when the percentage of free PSA is low
- Men with a PSA change ≥ 2 ng/ml in the = year before=20 diagnosis have a 15% 10-yr mortality; less dramatic PSA changes = indicate a=20 negligible mortality
ACS recommendation
- Men > 50 yr with a life expectancy of = > 10 yr:=20 annual DRE and PSA test
- High-risk men (i.e., African Americans and = men with=20 family history of prostate cancer): annual screening beginning at = age 40 yr=20

Diagnosis=20

Biopsy, guided by transrectal ultrasonography =
- Further biopsies if prostate intraepithelial = neoplasia=20 is present=20
- Histologic grading=20
- Gleason score: tumors are graded from 1 = (least=20 malignant) to 5 (most malignant) on the basis of architectural = patterns in=20 the examined tissue; grades reflecting the two most common = architectural=20 patterns are added to create the Gleason score=20
  - Correlates with clinical prognosis and is = used in=20 stratifying patients
  - Most tumors are Gleason 6 or 7=20
Clinical staging
- Useful for distinguishing between localized = and=20 locally advanced tumors, but otherwise of limited value in judging=20 curability or extent of disease or in determining appropriate=20 treatment
TNM classification=20
- T1 and T2 tumors: localized, detected by = transurethral=20 resection, generally indolent=20
- T3 and T4 tumors: rarely cured by surgery or = radiation=20 therapy alone
Multifactorial staging
- Combines clinical stage, serum PSA level, = and Gleason=20 score
- Most clinically useful way to stratify by = prognosis=20
- Risk of biochemical (PSA) relapse after = local=20 therapy=20
  - Low (> 85% 5-yr PSA failure-free = survival): T1c=20 or T2a, and PSA ≤ 10 ng/ml, and Gleason score ≤ = 6=20
  - Medium (50% 5-yr PSA failure-free = survival): T2b, or=20 PSA > 10 and ≤ 20 ng/ml, or Gleason score =3D 7=20
  - High (22% 5-yr PSA failure-free survival): = T2c, or=20 PSA > 20 ng/ml, or Gleason score ≥ 8 =
Staging based on imaging
- Not useful for most patients
- Bone scans to assess skeletal involvement = and CT or=20 MRI scans to assess regional lymph nodes may be useful in men with = serum PSA=20 > 10 ng/ml, Gleason score 8=9610, or locally advanced cancer (T3 = or=20 T4)

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Best=20 Therapy

No Therapy =

Risk of prostate cancer mortality=20
- Gleason score ≥ 7 and age ≤ 74 = yr: significant=20 risk=20
- Gleason score ≤ 6 at any age: minimal = to modest risk=20

Treatment of = Localized Prostate=20 Cancer

Treatment decisions are based on patient and = physician=20 preferences, attitudes toward treatment-related side effects, and=20 comorbidity=20
- Radical prostatectomy: side effects include = urinary=20 incontinence and, frequently, erectile dysfunction=20
- Radiation therapy: side effects include = erectile=20 dysfunction and rectal injury resulting in changes in bowel = function=20
  - Brachytherapy: easily administered, = apparently=20 favorable toxicity profile, promising cancer-control rates; = implant=20 placement may leave cold spots where cancer persists=20
  - External-beam radiation: the standard dose = may be=20 insufficient to eradicate all cancer =

Treatment Selection by Risk of Recurrence (See = Multifactorial=20 Staging, above)=20

Low-risk patients: outcomes are generally = excellent,=20 regardless of therapy=20
Intermediate-risk patients=20
- Higher likelihood of occult metastatic = disease=20
- Surgery is curative in about 50% of cases, = but many=20 will require further therapy because of recurrent or persistent = local cancer=20 or because of distant metastases=20
- Concomitant androgen ablation in conjunction = with=20 radiation may be beneficial
High-risk patients=20
- Highest likelihood of occult metastatic = disease=20
- Local therapy alone is rarely curative, so = the=20 morbidity of radical prostatectomy is difficult to justify=20
- Many such patients receive androgen ablation = followed=20 by external-beam radiation therapy, although long-term results are=20 poor

Treatment of = Advanced=20 Prostate Cancer

Salvage Treatment=20

Relapse after radical prostatectomy=20
- Patients who can be successfully treated = with=20 radiation therapy are those with organ-confined cancer at the time = of=20 initial treatment, increased PSA levels occurring > 2 yr after = surgery,=20 and a serum PSA level < 1 ng/ml at time of salvage therapy =
Relapse after initial radiation therapy =
- Salvage radical prostatectomy is associated = with very=20 high morbidity
Before either salvage treatment, restage with = bone scan,=20 CT scan, MRI, and possibly scintigraphy

Androgen Ablation

Standard initial treatment for advanced = prostate cancer=20
Side effects=20
- Hot flashes
- Loss of libido
- Impotence=20
- Gain of adipose tissue
- Loss of muscle and bone mass=20
- Likely modest increase in cardiovascular = events=20
May slow progression of disease and prolong = survival=20 when begun with primary treatment
Different modalities have equivalent impact on = survival,=20 although antiandrogen monotherapy is inferior to the others in = patients with=20 metastases=20
- Orchiectomy=20
- Luteinizing hormone-releasing hormone (LHRH) = agonists=20 leuprolide or goserelin, administered either monthly or every 3 or 4 = mo=20
- Antiandrogens (flutamide, bicalutamide, = nilutamide),=20 mostly used with chemical or surgical castration=20
  - Disease typically recurs, indicated by = rise in serum=20 PSA level=20
  - Duration of response is ~ 12=9618 mo in = patients with=20 overt metastatic disease and much longer in men without = metastases=20
- Estrogen: side effects include gynecomastia = and=20 thromboembolic phenomena

Chemotherapy for Hormone-Refractory = Prostate=20 Cancer=20

Docetaxel plus prednisone: standard = chemotherapy for=20 metastatic prostate cancer=20
Mitoxantrone plus a corticosteroid: has = produced=20 improvements in quality of life but not in survival=20
Taxanes (paclitaxel, docetaxel): longer = survival has=20 been demonstrated for treatment with docetaxel than with mitoxantrone = plus=20 prednisone

Palliation of Bone = Pain in=20 Advanced Disease=20

Analgesics (NSAIDs and narcotics)=20
External-beam radiation therapy=20
Radiopharmaceuticals (strontium-89, = samarium-153=96labeled=20 EDTMP)=20
- Generally well tolerated=20
- Progressive marrow suppression may occur = with repeat=20 dosing

The author has no commercial = relationships with=20 manufacturers of products or providers of services discussed in this=20 module.=20

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Best References

Bill-Axelson A, et al: N Engl J Med 352:1977, = 2005 [PMID=20 15888698]

Partin AW, et al: JAMA 277:1445, 1997 [PMID = 9145716]=20

Thompson IM, et al: N Engl J Med 350:2239, 2004 = [PMID=20 15163773]

November=20 2006