Relationship between systematic biopsies and histological features of 222 radical prostatectomy specimens: lack of prediction of tumor significance for men with nonpalpable prostate cancer.

PURPOSE: Because of the recent increase in nonpalpable prostate cancer (clinical stage T1c) in men, preoperative needle biopsy findings have had an important role for treatment decisions. We examine the correlation among histopathological features of 6 systematic biopsies and radical prostatectomy specimens in which 1 investigator reviewed all histological sections. MATERIALS AND METHODS: We studied a total of 450 men with clinical stage T1c prostate cancer from whom needle biopsies were matched with radical prostatectomy specimens, and selected 222 patient biopsies that were obtained from 6 or more separate regions of the prostate. The pretreatment parameters of serum prostate specific antigen (PSA), PSA density, number of positive needle biopsies, distribution of positive cores, linear cancer length, and percent Gleason grade 4/5 on the biopsy were determined and compared with histopathological features of prostate cancer in the radical prostatectomy specimens. All biopsies and radical prostatectomies were evaluated morphologically at the department of urology. RESULTS: Of the 222 men the largest cancer was clinically insignificant in 23 (10%), as measured by a cancer volume of less than 0.5 cc. Cancer volume in the prostatectomy specimen was significantly related to all parameters in the biopsy, with the surprising exception of cancer distribution in the positive biopsies. However, all of these correlations with cancer volume were weak, with Pearson's correlation squared (R(2)) multiplied by 100 less than 10%. Unfortunately, tumor grade on the biopsy agreed with the prostatectomy specimen in only 81 of 222 (36%) cases. Grade assessment with needle biopsy underestimated the tumor grade in 102 (46%) cases and overestimated it in 39 (18%). No single parameter in the biopsy was a predictor of tumor significance, as measured by a cancer volume of greater than 0.5 cc. However, the best model to predict a tumor less than 0.5 cc in volume was the combination of a single positive core with cancer length less than 3 mm. that contained no Gleason grade 4/5. The use of PSA or PSA density in combination with needle biopsy findings did not enhance prediction of tumor significance. CONCLUSIONS: These results indicate a weak and disappointing correlation among all pathological features of 6 systematic biopsies and radical prostatectomy specimens. The combination of 1 positive core with cancer length less than 3 mm. that contains no Gleason grade 4/5 is probably the best predictor of prostate cancer less than 0.5 cc in men with nonpalpable tumors, a cancer volume that occurred in only 10% of the 222 (23) men.

Preoperative serum prostate specific antigen does not reflect biochemical failure rates after radical prostatectomy in men with large volume cancers.

PURPOSE: We compared pathological findings with prostate specific antigen (PSA) failure rates following radical prostatectomy for large volume cancers (6 cc or greater). MATERIALS AND METHODS: A total of 191 men whose radical prostatectomy specimen had a cancer volume of 6 cc or greater were followed for a mean of 3.6 years (range 0.3 to 11.1) and 112 (58.6%) had PSA failure (PSA 0.07 ng./ml. or greater and increasing). Percent Gleason grade 4/5 (the Stanford modified Gleason scale), cancer volume, seminal vesicle invasion, regional lymph nodes, capsular penetration, positive surgical margin, location of the largest cancer in the peripheral or transition zone, prostate weight, patient age, preoperative PSA and clinical stage were analyzed using univariate and multivariate Cox proportional hazards analyses. RESULTS: In univariate regression analysis percent Gleason grade 4/5, lymph node involvement, cancer volume, cancer location in the peripheral zone, capsular penetration and positive surgical margins were significant predictors of biochemical failure. Seminal vesicle invasion, preoperative serum PSA, patient age, prostate weight and clinical stage were not statistically significant. Forward stepwise, multivariate analysis showed that percent Gleason grade 4/5 (p <0.0001, relative risk ratio 2.498), cancer location in the peripheral zone (p = 0.0097, 1.887), cancer volume (p = 0.0157, 1.691) and lymph node involvement (p = 0.0317, 1. 666) were the only independent predictors of biochemical failure. When 52 men with organ confined, large volume prostate cancer were analyzed separately, univariate and multivariate analyses showed that only cancer location in the peripheral zone (p = 0.0021, relative risk ratio 13.473) and percent Gleason grade 4/5 (p = 0. 0449, 4.111) were independent predictors of failure. CONCLUSIONS: Percent Gleason grade 4/5, cancer location in the peripheral zone, cancer volume and lymph node involvement have prognostic value in large volume prostate cancer. Cancer location in the peripheral zone and percent Gleason grade 4/5 are the most powerful predictors of biochemical failure in men whose cancer is 6 cc or greater and contained in the prostatic capsule. Preoperative serum PSA is not helpful in distinguishing biochemical failure rates in these large volume cancers whether they are organ confined or not.

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) failure can be accurately predicted from preoperative serum PSA combined with 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 zone cancers treated only with radical retropubic prostatectomy were followed for a minimum of 3 years (mean and median greater than 5). All prostates were sectioned at 3 mm. intervals and morphological variables were quantitated using the Stanford technique. Biochemical failure was defined as serum PSA 0.07 ng./ml. or greater and increasing. Multivariate logistic regression was used to identify variables with the most independent influence on biochemical failure and derive a clinical equation to predict failure in peripheral zone cancers. The validity of the predictive equation was assessed by out 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 after 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 biochemically free of disease. Only 15.8% of 57 men with PSA greater than 15 ng./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 important variables predicting biochemical disease-free status for peripheral zone cancers were percent Gleason grade 4/5, cancer volume, serum PSA and prostate weight. Foci of vascular invasion, intraductal cancer and lymph nodes were less significant variables, and capsular penetration, positive surgical margins and seminal vesical invasion were insignificant. The multivariate 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 variables from the prostatectomy specimen and serum PSA. The level of serum PSA profoundly limits biochemical cure rates in peripheral zone cancers. Transition zone cancers have a high cure rate, despite high serum PSA and adverse morphological variables. Men with serum PSA greater than 15 and perhaps even greater than 10 ng./ml. have such a low cure rate for peripheral zone cancer that re-biopsy attempts appear indicated to prove a transition zone location 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 of cure with radical prostatectomy procedures, as 85% of all tumors are in the peripheral zone.

Biological determinants of cancer progression in men with prostate cancer.

CONTEXT: The recent increase in ability to diagnose prostatic adenocarcinoma has created a dilemma for treatment decisions. OBJECTIVE: To determine whether prostate cancer progression is associated with a modified version of the Gleason grading system together with selected morphologic and clinical variables. DESIGN: Retrospective analysis of a cohort of patients with peripheral zone prostate cancers who underwent surgery between August 1983 and July 1992. SETTING: University hospital. PATIENTS: Radical prostatectomy specimens from 379 men treated only by surgical excision were prospectively studied for 8 morphologic variables using previously standardized techniques. Variables were percentage of each cancer occupied by Gleason grade 4/5 (% Gleason grade 4/5, the Stanford modified Gleason scale), cancer volume, vascular invasion, lymph node involvement, seminal vesicle invasion, capsular penetration, positive surgical margin, prostate weight, and preoperative prostate-specific antigen (PSA) level. MAIN OUTCOME MEASURE: Biochemical progression of prostate cancer as indicated by serum PSA level of 0.07 ng/mL and increasing. RESULTS: Cancer grade expressed as % Gleason grade 4/5 and cancer volume were highly predictive of disease progression. In a Cox proportional hazards model that included % Gleason grade 4/5, the traditional Gleason score was not an independent predictor of treatment failure. Positive lymph node findings and intraprostatic vascular invasion were the only other variables that remained significant at the .01 level. CONCLUSION: The % Gleason grade 4/5, cancer volume, positive lymph node findings, and intraprostatic vascular invasion were independently associated with prostate cancer progression, defined by an increasing PSA level. Techniques to accurately measure cancer volume and % Gleason grade 4/5 are needed to better predict which patient will experience cancer progression. The commonly accepted predictors of progression-capsular penetration and positive surgical margins-were not independently predictive of failure after radical prostatectomy.

Classification of localized untreated prostate cancer based on 791 men treated only with radical prostatectomy: common ground for therapeutic trials and TNM subgroups.

PURPOSE: We examined cancer volume, percent Gleason grade 4/5 cancer, cancer location (peripheral versus transition zone), capsular penetration and biochemical cure rates in men undergoing radical prostatectomy to determine differences among clinical stages T1c, T2a, T2b and T2c. MATERIALS AND METHODS: Detailed chart reviews confirmed the precise clinical stages assigned to 791 consecutive men treated only with radical prostatectomy. All prostates were examined prospectively by the Stanford technique of 3 mm. step sections. For biochemical cure rates a subset of 366 men were followed for a minimum of 5 years. Failure was defined as prostate specific antigen Tosoh 0.07 ng./ml. or greater and rising. T1c was defined as impalpable cancer. RESULTS: T1c and T2a stages had half as much cancer volume as T2b and T2c cancers, 10 versus 25% Gleason grade 4/5 and half as much capsular penetration (30 versus 61%). Biochemical cure rates were 70 and 72% for T1c and T2a compared to 37 and 27% for T2b and T2c, respectively. Of T1c cancers 25% were in the transition zone compared to 7.9 to 9.9% of T2a to c cancers. CONCLUSIONS: T1c cancers are similar to T2a cancers in tumor volume and percent Gleason grade 4/5, the primary determinants of therapeutic failure. Minimal 5-year cure rates for T1c and T2a cancers are similar. Transition zone cancers are 2.5 times more common in T1c cancers than in palpable T2 tumors. T2a cancers like T1c cancers are highly favorable tumors and should be retained in TNM classifications. These data suggest that the 4 clinical stages of T1c to T2c can serve as a valid basis for comparing different therapeutic strategies.