Longitudinal assessment of urinary PCA3 for predicting prostate cancer grade reclassification in favorable-risk men during active surveillance.

BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS). METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate magnetic resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ⩾3 years of monitoring were included. Utility of first PCA3 score (fPCA3), subsequent PCA3 (sPCA3) and change in PCA3 were assessed for prediction of Gleason grade reclassification (GR, Gleason score >6) during follow-up. RESULTS: In total, 260 men met study criteria. Median time from enrollment to fPCA3 was 2 years (interquartile range (IQR) 1-3) and from fPCA3 to sPCA3 was 5 years (IQR 4-6). During median follow-up of 6 years (IQR 5-8), 28 men (11%) underwent GR. Men with GR had higher median fPCA3 (48.0 vs 24.5, P=0.007) and sPCA3 (63.5 vs 36.0, P=0.002) than those without GR, while longitudinal change in PCA3 did not differ by GR status (log-normalized rate 0.07 vs 0.06, P=0.53). In a multivariable model including age, risk classification and PSA density, fPCA3 remained significantly associated with GR (log(fPCA3) odds ratio=1.77, P=0.04). CONCLUSIONS: PCA3 scores obtained during AS were higher in men who underwent GR, but the rate of change in PCA3 over time did not differ by GR status. PCA3 was a significant predictor of GR in a multivariable model including conventional risk factors, suggesting that PCA3 provides incremental prognostic information in the AS setting.

Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice.

BACKGROUND: The Prostate Health Index (phi) outperforms PSA and other PSA derivatives for the diagnosis of prostate cancer (PCa). The impact of phi testing in the real-world clinical setting has not been previously assessed. METHODS: In a single, large, academic center, phi was tested in 345 patients presenting for diagnostic evaluation for PCa. Findings on prostate biopsy (including Grade Group (GG), defined as GG1: Gleason score (GS) 6, GG2: GS 3+4=7, GG3: GS 4+3=7, GG4: GS 8 and GG5: GS 9-10), magnetic resonance imaging (MRI) and radical prostatectomy (RP) were prospectively recorded. Biopsy rates and outcomes were compared with a contemporary cohort that did not undergo phi testing (n=1318). RESULTS: Overall, 39% of men with phi testing underwent prostate biopsy. No men with phi<19.6 were diagnosed with PCa, and only three men with phi<27 had cancer of GG⩾2. Phi was superior to PSA for the prediction of any PCa (area under the receiver operating characteristic curve (AUC) 0.72 vs 0.47) and GG⩾2 PCa (AUC 0.77 vs 0.53) on prostate biopsy. Among men undergoing MRI and phi, no men with phi<27 and PI-RADS⩽3 had GG⩾2 cancer. For those men proceeding to RP, increasing phi was associated with higher pathologic GG (P=0.002) and stage (P=0.001). Compared with patients who did not undergo phi testing, the use of phi was associated with a 9% reduction in the rate of prostate biopsy (39% vs 48%; P<0.001). Importantly, the reduction in biopsy among the phi population was secondary to decreased incidence of negative (8%) and GG1 (1%) biopsies, whereas the proportion of biopsies detecting GG⩾2 cancers remained unchanged. CONCLUSIONS: In this large, real-time clinical experience, phi outperformed PSA alone, was associated with high-grade PCa, and provided complementary information to MRI. Incorporation of phi into clinical practice reduced the rate of unnecessary biopsies without changing the frequency of detection of higher-grade cancers.

Unscreened older men diagnosed with prostate cancer are at increased risk of aggressive disease.

BACKGROUND: To evaluate the relationship between PSA testing history and high-risk disease among older men diagnosed with prostate cancer. METHODS: Records from 1993 to 2014 were reviewed for men who underwent radiotherapy for prostate cancer at age 75 years or older. Patients were classified into one of four groups based on PSA-testing history: (1) no PSA testing; (2) incomplete/ineffective PSA testing; (3) PSA testing; or (4) cannot be determined. Outcomes of interest were National Comprehensive Cancer Network (NCCN) risk group (that is, low, intermediate or high risk) and biopsy grade at diagnosis. Multivariable logistic regression was used to determine the association between PSA testing history and high-risk cancer. RESULTS: PSA-testing history was available in 274 (94.5%) of 290 subjects meeting study criteria. In total, 148 men (54.0%) underwent PSA testing with follow-up biopsy, 72 (26.3%) underwent PSA testing without appropriate follow-up, and 54 men (19.7%) did not undergo PSA testing. Patients who underwent PSA testing were significantly less likely to be diagnosed with NCCN high-risk cancer (23.0% vs 51.6%, P<0.001). On multivariable analysis, men with no/incomplete PSA testing had more than three-fold increased odds of high-risk disease at diagnosis (odds ratio 3.39, 95% confidence interval 1.96-5.87, P<0.001) as compared to the tested population. CONCLUSIONS: Older men who underwent no PSA testing or incomplete testing were significantly more likely to be diagnosed with high-risk prostate cancer than those who were previously screened. It is reasonable to consider screening in healthy older men likely to benefit from early detection and treatment.

Resection of isolated renal cell carcinoma metastases of the pancreas: outcomes from the Johns Hopkins Hospital.

PURPOSE: This study aims to assess outcomes and characteristics associated with resection of metastatic renal cell carcinoma (mRCC) to the pancreas. MATERIALS AND METHODS: From April 1989 to July 2012, a total of 42 patients underwent resection of pancreatic mRCC at our institution. We retrospectively reviewed records from a prospectively managed database and analyzed patient demographics, comorbidities, perioperative outcomes, and overall survival. Cox proportional hazards models were used to evaluate the association between patient-specific factors and overall survival. RESULTS: The mean time from resection of the primary tumor to reoperation for pancreatic mRCC was 11.2 years (range, 0-28.0 years). In total, 17 patients underwent pancreaticoduodenectomy, 16 underwent distal pancreatectomy, and 9 underwent total pancreatectomy. Perioperative complications occurred in 18 (42.9%) patients; there were two (4.8%) perioperative mortalities. After pancreatic resection, the median follow-up was 7.0 years (0.1-23.2 years), and median survival was 5.5 years (range, 0.4-21.9). The overall 5-year survival was 51.8%. On univariate analysis, vascular invasion (hazard ratio, 5.15; p = 0.005) was significantly associated with increased risk of death. CONCLUSIONS: Pancreatic resection of mRCC can be safely achieved in the majority of cases and is associated with long-term survival. Specific pathological factors may predict which patients will benefit most from resection.