Prostate cancer is highly predictable: A prognostic equation based on all morphological variables in radical prostatectomy specimens

Purpose: We determine whether biochemical prostate specific antigen (PSA) f ailure can be accurately predicted from preoperative serum PSA combined wit h 6 morphological variables from radical retropubic prostatectomy specimens in men with peripheral zone cancers. The unexpected limitation imposed by preoperative serum PSA on biochemical failure led us to compare peripheral zone to transition zone cancers. Materials and Methods: A total of 326 peripheral zone and 46 transition zon e cancers treated only with radical retropubic prostatectomy were followed for a minimum of 3 years (mean and median greater than 5). All prostates we re sectioned at 3 mm. intervals and morphological variables were quantitate d using the Stanford technique. Biochemical failure was defined as serum PS A 0.07 ng./ml. or greater and increasing. Multivariate logistic regression was used to identify variables with the most independent influence on bioch emical failure and derive a clinical equation to predict failure in periphe ral zone cancers. The validity of the predictive equation was assessed by o ut of sample validation and cross validation techniques. The 46 transition zone cancers were compared to the 326 peripheral zone cancers by Student's t and Wilcoxon tests. Results: Of the peripheral zone failures 60% occurred in the first year aft er radical retropubic prostatectomy and 95% had occurred by the end of year 4. The highest preoperative serum PSA was 23 ng./ml. among the 181 men bio chemically free of disease. Only 15.8% of 57 men with PSA greater than 15 n g./ml. were biochemically disease-free. For the 48 transition zone cancers cure rates were independent of serum PSA with 6 men having PSA greater than 50 ng./ml. Biochemical disease-free status was noted in 80% of transition zone compared to 56% of peripheral zone cancers (p = 0.0009). The most impo rtant variables predicting biochemical disease-free status for peripheral z one cancers were percent Gleason grade 4/5, cancer volume, serum PSA and pr ostate weight. Foci of vascular invasion, intraductal cancer and lymph node s were less significant variables, and capsular penetration, positive surgi cal margins and seminal vesical invasion were insignificant. The multivaria te logistic equation for predicting failure in peripheral zone cancers was highly accurate and requires only 2 to 3 minutes with a simple calculator. Conclusions: Failure of radical retropubic prostatectomy to cure peripheral zone prostate cancer is highly predictable based on 6 morphological variab les from the prostatectomy specimen and serum PSA. The level of serum PSA p rofoundly limits biochemical cure rates in peripheral zone cancers. Transit ion zone cancers have a high cure rate, despite high serum PSA and adverse morphological variables. Men with serum PSA greater than 15 and perhaps eve n greater than 10 ng./ml. have such a low cure rate for peripheral zone can cer that re-biopsy attempts appear indicated to prove a transition zone loc ation or else therapy other than radical retropubic prostatectomy should be sought. Pathologists should indicate whether the primary (largest) cancer is in the peripheral or transition zone to prevent overoptimistic reports o f cure with radical prostatectomy procedures, as 85% of all tumors are in t he peripheral zone.