Faculty Bibliography

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.

OBJECTIVES: To examine the treatment outcomes of men who would have been eligible for active surveillance (AS) but underwent immediate radical retropubic prostatectomy (RRP). AS protocols are designed to spare the potential morbidity of treatment to patients with low-risk prostate cancer (PCa). METHODS: From a prospective RRP database, we evaluated the tumor features and treatment outcomes for men who would have met 1 of 3 published AS criteria: (1) clinically localized disease, Gleason < or = 7, and no significant comorbidities (Patel et al, J Urol. 2004;171:1520-1524) (2) T1b-T2b N0M0 disease, Gleason < or = 7, and prostate-specific antigen < or = 15 ng/mL (Choo R et al. J Urol. 2002;167:1664-1669), or (3) T1c PCa (Mohler JL et al. World J Urol. 1997;15:364-368.). RESULTS: 3959, 3536, and 2330 RRP patients, respectively, would have met these AS criteria. At surgery, 3%-4% had a Gleason score of 8-10, 16%-19% had positive surgical margins, 15%-18% had extracapsular tumor extension, 3%-5% had seminal vesicle invasion, and 0.4%-1% had lymph node metastasis. The 5-year progression-free survival rate ranged from 84%-89%. Metastasis occurred in 0.1%-1.2%, and 0.1%-0.9% died of PCa. On multivariate analysis, Gleason score > 6 was the strongest predictor of biochemical progression. CONCLUSIONS: A substantial proportion of men who might have been considered potential AS candidates had aggressive tumor features at RRP and/or progression. Biopsy Gleason score > 6 was the strongest predictor of adverse outcomes, highlighting the importance of limiting AS to patients with Gleason < or = 6. Overall, the accurate identification of patients with truly indolent PCa at the time of diagnosis remains challenging.

PURPOSE: A controversy of current prostate specific antigen based prostate cancer screening is the over detection of potentially insignificant prostate cancer. Because PSA kinetics were previously linked to prostate cancer specific mortality, we determined whether prostate specific antigen velocity is associated with clinically significant prostate cancer. MATERIALS AND METHODS: A total of 1,073 men underwent radical prostatectomy from 1992 to 2008 with data available on prostate specific antigen velocity and tumor volume. Insignificant cancer was defined by the Ohori criteria as organ confined, tumor volume 0.5 cc or less and no primary or secondary Gleason pattern 4 or 5. We calculated the proportion of men with pathologically insignificant prostate cancer stratified by prostate specific antigen velocity. RESULTS: Preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year was significantly associated with high grade disease (p = 0.008), positive surgical margins (p = 0.003) and seminal vesicle invasion (p = 0.007) at radical prostatectomy. Median tumor volume was also significantly higher in men with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year (3.1 vs 2.4 cc, p = 0.0001). Overall 69 men (6%) met the Ohori criteria for insignificant cancer. Patients with preoperative prostate specific antigen velocity greater than 0.4 ng/ml per year were 50% less likely to have insignificant disease (10% vs 5%, p = 0.003). CONCLUSIONS: A prostate specific antigen velocity threshold of 0.4 ng/ml per year was associated with the likelihood of insignificant prostate cancer. This suggests that prostate specific antigen velocity may be a useful adjunct in prostate cancer screening to increase specificity for identifying patients with clinically significant disease.