Radical prostatectomy for carcinoma of the prostate.

Morphologic features of prostatic adenocarcinoma in the radical prostatectomy (RP) specimen are powerful prognostic indicators for prognosis for disease-free survival. This review discusses the methods of sampling of the RP specimen to optimize the detection of these morphologic features, balanced against the added expense of submitting the entire gland for sectioning. Gleason grade, one of the most powerful prognostic factors, is discussed briefly, including the percent pattern 4/5 cancer compared to the standard Gleason grading. Pathologic stage, as defined by the TNM system, is discussed in detail, both in terms of precise histological definition of each category, as well as the associated prognostic implications. Surgical margin status is also important prognostically across all pathologic stages categories. Perineural invasion, which has been used diagnostically in prostate cancer for several decades, has emerged as a very important prognostic indicator as well, as determined by the quantitative aspects of tumor in the perineural space. The effect of tumor volume on prognosis is discussed, as well as the newer concepts of the prognostic significance of zone of origin of the tumor and the presence or absence of intraductal carcinoma.     

Predicting tumor volume in radical prostatectomy specimens from patients with prostate cancer

Tumor volume has prognostic value in numerous malignant neoplasms; however, the determination of tumor volume in prostatic adenocarcinoma remains problematic. We tested the hypothesis that the diameter of the largest focus of carcinoma in whole-mount prostate sections predicts the volume of adenocarcinoma in the entire prostate. We evaluated 184 radical prostatectomy specimens by whole-mount processing of the entire prostate. The maximum diameter of the largest focus of carcinoma was measured directly on glass slides. Tumor volume in the entire prostate was calculated by the grid method. The maximum tumor diameter ranged from 0.1 to 4.1 cm (median, 1.6 cm). The total tumor volume ranged from 0.1 to 12.5 cm3 (median, 1.6 cm3). There were significant correlations between maximum tumor diameter and tumor volume (Spearman correlation coefficient = 0.84; P < .0001), surgical margin status (P < .001), perineural invasion (P < .001), serum prostate-specific antigen level at diagnosis (P = .004), Gleason score (P = .004), and pathologic stage (P < .0001). Maximum tumor diameter is a predictor of tumor volume and might be useful for the assessment of tumor volume in routinely processed prostatectomy specimens.     

Protein-coding and microRNA biomarkers of recurrence of prostate cancer following radical prostatectomy

An important challenge in prostate cancer research is to develop effective predictors of tumor recurrence following surgery to determine whether immediate adjuvant therapy is warranted. To identify biomarkers predictive of biochemical recurrence, we isolated the RNA from 70 formalin-fixed, paraffin-embedded radical prostatectomy specimens with known long-term outcomes to perform DASL expression profiling with a custom panel that we designed of 522 prostate cancer-relevant genes. We identified a panel of 10 protein-coding genes and two miRNA genes (RAD23B, FBP1, TNFRSF1A, CCNG2, NOTCH3, ETV1, BID, SIM2, LETMD1, ANXA1, miR-519d, and miR-647) that could be used to separate patients with and without biochemical recurrence (P < 0.001), as well as for the subset of 42 Gleason score 7 patients (P < 0.001). We performed an independent validation analysis on 40 samples and found that the biomarker panel was also significant at prediction of biochemical recurrence for all cases (P = 0.013) and for a subset of 19 Gleason score 7 cases (P = 0.010), both of which were adjusted for relevant clinical information including T-stage, prostate-specific antigen, and Gleason score. Importantly, these biomarkers could significantly predict clinical recurrence for Gleason score 7 patients. These biomarkers may increase the accuracy of prognostication following radical prostatectomy using formalin-fixed specimens.     

Markers for the development of early prostate cancer

Biochemical and genetic changes precede histologically identifiable changes accompanying cell transformation often by months or years. De-expression of the extracellular matrix adhesive glycoprotein tenascin and the cell-to-cell adherent protein E-cadherin have been suggested as markers of early neoplastic change in prostate epithelial cells. Previous studies have been inconclusive, probably due to epitope masking. This study examined 2,378 biopsy cores from 289 prostates using a heat antigen retrieval protocol at low pH to improve the accuracy of detection. Tenascin and E-cadherin de-expression was correlated with purinergic receptor and telomerase-associated protein labelling, as well as prostate-specific antigen (PSA) levels and Gleason scores. E-cadherin was a poor marker, as it was expressed in all lesions except carcinomas of the highest Gleason score. Tenascin was maximally expressed in the extracellular matrix and acinar basement membrane in normal and prostatic intraepithelial neoplasia tissue. In prostate cancer tissue, tenascin expression did not correlate with Gleason score but was significantly de-expressed as purinergic receptor and telomerase-associated protein expression increased. Marked changes in tenascin, telomerase-associated protein, and purinergic receptor expression were apparent before any histological abnormalities were visible by haematoxylin and eosin (H&E) stain, making these potential markers for early and developing prostate cancer. Moreover, the potential increased accuracy of diagnosis of underlying prostate cancer using purinergic receptor translocation (PRT) assessment suggests that PSA levels may be more accurate than has generally been supposed when apparent false negatives arising from H&E-based diagnoses are correctly categorized.     

Prognostic factors in prostate cancer. Key elements in structured histopathology reporting of radical prostatectomy specimens

Prostate cancer is the most common visceral cancer and the second most common cause of cancer death in males. The number of radical prostatectomies performed each year is increasing and accurate data from the histopathological examination of these specimens aid clinicians in stratifying patients for surveillance and adjuvant therapies. This review focuses on the histopathological prognostic factors which should be routinely recorded in pathology reports and complements the Royal College of Pathologists of Australasia Structured Reporting Protocol for Prostate Cancer (Radical Prostatectomy). Such structured pathology reports have been shown to significantly enhance the completeness and quality of data provided to clinicians. The review also discusses the International Society for Urological Pathology Consensus Conference recommendations which were published recently.     

Radical prostatectomy: lower rates among African-American men.

This study compares radical prostatectomy rates by race among male Medicare patients in New York. A retrospective analysis was conducted of all radical prostatectomies performed on hospitalized male Medicare beneficiaries for the period 1991 through 1993. Basic trend data also were analyzed for 1990. Pattern analysis was conducted on the 4154 procedures performed between 1990 and 1993. The rate of radical prostatectomy rose dramatically during the 3-year period from 1990 to 1992 among New York''s 1.1 million male Medicare beneficiaries. The rates rose for both African Americans and whites. However, the annual rates of radical prostatectomy for African Americans were significantly below those for whites. Lower rates of radical prostatectomies were observed for African Americans in all age groups except the < 65-year-old group. However, the total number of radical prostatectomies in this age group were small in number. An important finding was the lower annual rates of radical prostatectomy for African Americans in the 65- to 69-year-old age group. During the period under study, prostate cancer among Medicare patients in New York rose by 33.8% for African Americans and 26.5% for whites. Significantly, local disease was found at the time of diagnosis in 70% of whites but in only 55% of African Americans. These data reflect later stage at diagnosis among African-American males. These results indicate that despite higher national rates for prostate cancer, male African-American Medicare patients in New York have reduced access to radical prostatectomy as a treatment modality. This is especially of importance in the < 70-year-old group in whom most authorities consider the procedure appropriate. The reasons for this reduced access are discussed as are the measures needed to remedy the underlying inequities in health care.     

Nomogram to predict insignificant prostate cancer at radical prostatectomy in Korean men: a multi-center study

Purpose

Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC.

Materials and Methods

The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort.

Results

Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827.

Conclusion

Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are considered.