Faculty Bibliography

OBJECTIVE: To further examine the association between statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) and pathological features in a large group of patients undergoing radical prostatectomy (RP), as epidemiological studies have suggested that statins, in addition to their beneficial cardiovascular effects, might reduce the risk of aggressive prostate cancer. PATIENTS AND METHODS: From 2003 to 2009, 1351 men with data on preoperative statin use had RP by one surgeon. The clinical and pathological tumour features were compared between 504 users of statins and 847 who were not users. RESULTS: Statin users were significantly older and had a higher mean body mass index than non-users. The preoperative serum prostate-specific antigen levels, tumour volume and percentage of cancer in the RP specimen were significantly lower in patients taking statins. Overall, statin users had a proportionately lower rate of adverse tumour pathology features, including a significantly lower risk of positive (cancerous) surgical margins. CONCLUSION: Our results suggest that the use of statins might be associated with more favourable pathological features at RP. The long-term disease-specific outcomes and the underlying link between statins and prostate cancer require further investigation.

PURPOSE OF REVIEW: Prostate cancer is the most common noncutaneous malignancy among men in the USA and is most frequently diagnosed through prostate-specific antigen (PSA)-based screening. Nevertheless, PSA testing has become increasingly controversial. In this review, we will present the evidence supporting the role of PSA in prostate cancer screening. RECENT FINDINGS: Numerous studies have shown that the risk of current and future prostate cancer is directly related to the serum PSA level. Moreover, increasing PSA levels predict a greater risk of adverse pathologic features and worse disease-specific survival. Substantial epidemiologic evidence has suggested a reduction in advanced disease and improvements in prostate cancer survival rates since the introduction of PSA-based screening. Recently, evidence from a randomized trial further validated that PSA testing reduces both metastatic disease and prostate cancer-specific mortality. SUMMARY: PSA is a valid marker for prostate cancer and its aggressiveness. Level 1 evidence is now available that PSA-based screening reduces both the rate of metastatic disease and prostate cancer-specific mortality.

PURPOSE: Postoperative prostate specific antigen doubling time may be used as a surrogate for prostate cancer specific mortality in patients with biochemical recurrence after radical prostatectomy. Less is known about the usefulness of preoperative prostate specific antigen doubling time for the initial prediction of prostatectomy outcomes. MATERIALS AND METHODS: Preoperative prostate specific antigen doubling time was calculated in 1,208 men from a large prostate cancer screening study who were treated with radical prostatectomy. We examined the relationship of prostate specific antigen doubling time with tumor features and biochemical progression-free survival. RESULTS: Overall prostate specific antigen doubling time was associated with nonorgan confined disease (OR 0.996, 95% CI 0.992-0.999, p = 0.013) but not with biochemical progression (HR 1.000, 95% CI 0.998-1.001, p = 0.66). Using previously published 18 and 36-month thresholds for prostate specific antigen doubling time there was no significant relationship between doubling time and specific adverse pathological features or biochemical progression. Using the concordance index prostate specific antigen doubling time did not enhance the prediction of biochemical progression beyond that achieved by a model with prostate specific antigen, clinical stage and biopsy Gleason score. CONCLUSIONS: In our series of men with newly diagnosed, clinically localized prostate cancer shorter preoperative prostate specific antigen doubling time was associated with nonorgan confined disease but not with biochemical progression after radical prostatectomy. All calculations of prostate specific antigen kinetics may not be equivalent. Caution should be exercised when using prostate specific antigen doubling time in the pretreatment setting.

PURPOSE: Surgical treatment for prostate cancer represents a large national health care expenditure. We determined whether state level variation in the cost of radical prostatectomy exists and whether we could explain this variation by adjusting for covariates associated with cost. MATERIALS AND METHODS: Using the 2004 Healthcare Cost and Utilization Project National Inpatient Sample of 7,978,041 patients we identified 9,917 who were 40 years old or older with a diagnosis of prostate cancer who underwent radical prostatectomy without cystectomy. We used linear regression to examine state level regional variation in radical prostatectomy costs, controlling for the local area wage index, patient demographics, case mix and hospital characteristics. RESULTS: The mean +/- SD unadjusted cost was $9,112 +/- $4,434 (range $2,001 to $49,922). The unadjusted mean cost ranged from $12,490 in California to $4,650 in Utah, each significantly different from the mean of $8,903 in the median state, Washington (p <0.0001). After adjusting for all potential confounders total cost was highest in Colorado and lowest in New Jersey, which were significantly different from the median, Washington ($10,750 and $5,899, respectively, vs $8,641, p <0.0001). The model explained 85.9% of the variance with regional variation accounting for the greatest incremental proportion of variance (35.1%) and case mix variables accounting for an incremental 32.3%. CONCLUSIONS: The total cost of radical prostatectomy varies significantly across states. Controlling for known total cost determinants did not completely explain these differences but altered ordinal cost relationships among states. Cost variation suggests inefficiencies in the health care market. Additional studies are needed to determine whether these variations in total cost translate into differences in quality or outcome and how they may be translated into useful policy measures

PURPOSE: Due to the limited specificity of prostate specific antigen for prostate cancer screening, there is an ongoing search for adjunctive biomarkers. Retrospective studies have suggested that an isoform of proenzyme prostate specific antigen called [-2]proenzyme prostate specific antigen may enhance the specificity of prostate specific antigen based screening. We examined the usefulness of this isoform in a prospective prostate cancer screening study. MATERIALS AND METHODS: From a population of 2,034 men undergoing prostate cancer screening we examined the relationship between the measurement of the [-2]isoform of proenzyme prostate specific antigen (p2PSA) and prostate cancer detection. Specifically we compared the usefulness of total prostate specific antigen, the ratio of free-to-total prostate specific antigen, the ratio of p2PSA-to-free prostate specific antigen, and a formula combining prostate specific antigen, free prostate specific antigen and p2PSA (the Beckman Coulter prostate health index or phi) to predict prostate cancer in men from the study undergoing prostate biopsy with a prostate specific antigen of 2.5 to 10 ng/ml and nonsuspicious digital rectal examination. RESULTS: Despite similar total prostate specific antigen (p = 0.88), percent free prostate specific antigen (p = 0.02) and %p2PSA (p = 0.0006) distinguished between positive and negative biopsy results. On ROC analysis %p2PSA (AUC 0.76) outperformed prostate specific antigen (AUC 0.50) and percent free prostate specific antigen (AUC 0.68) for differentiating between prostate cancer and benign disease. Setting the sensitivity at 88.5%, p2PSA led to a substantial improvement in specificity as well as positive and negative predictive values. The Beckman Coulter prostate health index (AUC 0.77) had the best overall performance characteristics. CONCLUSIONS: This is the first prospective study to our knowledge to demonstrate that p2PSA provides improved discrimination between prostate cancer and benign disease in screened men with a prostate specific antigen of 2.5 to 10 ng/ml and a negative digital rectal examination.

Prostate-specific antigen (PSA) in combination with digital rectal examination forms the basis for current prostate cancer (CaP) screening programs. Although PSA screening was recently shown to reduce CaP-specific mortality in the European randomized trial, its limitations include the risk for unnecessary prostate biopsy and the diagnosis and treatment of some CaP that might never have caused suffering or death. A potential way to minimize these pitfalls is through the use of derivatives of PSA, particularly PSA kinetics, to increase the specificity for clinically relevant CaP. CaP is the second-leading cause of cancer death in men in the United States and many other westernized countries; accordingly, judicious screening of healthy men allows for diagnosis sufficiently early that all options (i.e., treatment or surveillance) are still available in most cases.

PURPOSE: PCA3 is a prostate specific noncoding mRNA that is significantly over expressed in prostate cancer tissue. Urinary PCA3 levels have been associated with prostate cancer grade and extent, suggesting a possible role in monitoring patients on active surveillance. We assessed the relationship between PCA3 and prostate biopsy results in men in a surveillance program. MATERIALS AND METHODS: Urine specimens were obtained from 294 men with prostate cancer enrolled in the Johns Hopkins surveillance program. The followup protocol included semiannual free and total prostate specific antigen measurements, digital rectal examination and annual surveillance prostate biopsy. Cox proportional hazards regression was used to evaluate the association between PCA3 results and progression on surveillance biopsy (defined as Gleason pattern 4 or 5, more than 2 positive biopsy cores or more than 50% involvement of any core with cancer). RESULTS: Patients with progression on biopsy (12.9%) had a mean PCA3 score similar to that of those without progression (60.0 vs 50.8, p = 0.131). ROC analysis suggested that PCA3 alone could not be used to identify men with progression on biopsy (AUC 0.589, 95% CI 0.496-0.683, p = 0.076). After adjustment for age and date of diagnosis PCA3 was not significantly associated with progression on biopsy (p = 0.15). CONCLUSIONS: In men with low risk prostate cancer who were carefully selected for surveillance the PCA3 score was not significantly associated with short-term biopsy progression. Further analysis is necessary to assess the usefulness of PCA3 in combination with other biomarkers or in selected subsets of patients undergoing surveillance.

Radical prostatectomy is the gold standard surgical treatment for clinically localized prostate cancer. Over the years, many different approaches to surgical removal of the prostate have been described. Today, the most common techniques are open radical retropubic prostatectomy and robotic-assisted laparoscopic radical prostatectomy. Although there are many differences between the 2 approaches, the common goal is to optimize oncologic and functional outcomes. This article highlights the background, techniques, and outcomes of open and robotic prostatectomy.