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The majority of prostate cancers are adenocarcinomas Most arise in the periphery of the prostate (peripheral zone), though a small percentage arise in the central (5 10%) and transition zones (20%) of the gland Most pathologists employ the Gleason grading system whereby a primary grade is applied to the architectural pattern of cancerous glands occupying the largest area of the specimen and a secondary pattern is assigned to the next largest area of cancerous growth Grading is based on architectural (rather than histologic) criteria, and five grades are possible Adding the score of the primary and secondary patterns gives a Gleason score Grade correlates well with tumor volume, stage, and prognosis The likelihood of success of surveillance or treatment can be predicted using risk assessment tools that combine stage,

Test Abnormal PSA (> 4 ng/mL) Abnormal DRE Abnormal PSA or DRE Abnormal PSA and DRE Sensitivity 067 050 084 034 Specificity 097 094 092 0995 Positive Predictive Value 043 024 028 049

DRE, digital rectal examination; PSA, prostate-specific antigen Modified, with permission, from Kramer BS et al Prostate cancer screening: what we know and what we need to know Ann Intern Med 1993 Nov 1;119(9):914 23

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grade, PSA level, and number and extent of positive prostate biopsies among other information Several tools are available on the Internet for private use (eg, http://mskccorg/ mskcc/html/5794cfm) One of the most widely used risk prediction tools is the Kattan nomogram; it uses tumor stage, grade, and PSA level to predict the likelihood that a patient will be disease-free at 5 years after radical prostatectomy or radiation therapy The CAPRA nomogram uses serum PSA, Gleason grade, clinical stage, percent positive biopsies and patient age in a point system to risk stratify patients and predict the likelihood of PSA recurrence three and five years after radical prostatectomy (Tables 39 7 and 39 8) The CAPRA has been validated on large multicenter radical prostatectomy cohorts The patterns of prostate cancer progression have been well defined The likelihood of both local invasion and metastases is greater in larger or less well-differentiated cancers Small and well-differentiated cancers (grades 1 and 2) are usually confined within the prostate, whereas large-volume (> 4 mL) or poorly differentiated (grades 4 and 5) cancers are more commonly locally extensive or metastatic to regional lymph nodes or bone Penetration of the prostate capsule by cancer is common and often occurs along perineural spaces Seminal vesicle invasion is associated with a high likelihood of regional or distant disease Lymphatic metastases are most often identified in the obturator and internal iliac lymph node chains The axial skeleton, as mentioned previously, is the most common site of distant metastases

Table 39 8 CAPRA: Probability of freedom from PSA recurrence after radical prostatectomy by CAPRA point total

3-year recurrence free survival (%)(95% CI) 91 (85 95) 89 (83 94) 81 (73 87) 81 (69 89) 69 (51 82) 54 (27 75) 24 (9 43) 5-year recurrence free survival (%) (95% CI) 85 (73 92) 81 (69 89) 66 (54 76) 59 (40 74) 60 (37 77) 34 (12 57) 8 (0 28)

What constitutes the optimal form of treatment for patients with clinically localized cancers remains controversial Treatment decisions are at present made on the basis of tumor grade and stage and the age and health of the patient

FIGURE 11-7

Although selected patients may be candidates for surveillance based on age or health and the presence of small-volume or well-differentiated cancers, most patients with an anticipated survival in excess of 10 years should be considered for treatment Both radiation therapy and radical prostatectomy allow for acceptable levels of local control The first large, prospective, randomized trial of watchful waiting compared with radical prostatectomy has been reported Six hundred ninetyfive men were randomized and monitored for a median of 82 years Radical prostatectomy reduced disease-specific mortality, overall mortality, and risks of metastasis and local progression The absolute reduction in the risk of death after 10 years was small, but the reductions in the risks of metastasis and local tumor progression were substantial This trial accrued patients in Sweden between 1989 and 1999, so the patients enrolled likely had a greater burden of disease than is average for patients who are newly diagnosed in areas where PSA screening is common Patients need to be advised of all treatment options (including surveillance) along with the particular benefits, risks, and limitations

Table 39 7 The UCSF Cancer of the Prostate Risk Assessment (CAPRA)

Variable PSA (ng/mL) Level 0 6 61 10 101 20 201 30 > 30 1 3/1 3 1 3/4 5 4 5/1 5 T1 or T2 T3a < 34% > 34% < 50 years > 50 years Points 0 1 2 3 4 0 1 3 0 1 0 1 0 1

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