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: 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

          • 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
          • 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

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