Best of AUA 2014: Prostate Cancer

Michael C. Gong, MD, PhD, presents the take home messages on prostate cancer from the AUA annual meeting in Orlando, FL, including new findings about enzalutamide (XTANDI).

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• After a median follow-up of 8.1 years in a large active surveillance cohort, about 40% of men had undergone delayed therapy and 1.5% had died from prostate cancer; the risk of dying from causes other than prostate cancer was nearly 10-fold higher. Similar results were reported in another large series that had a median follow-up of almost 5 years, and the investigators also reported PSA density was a predictor of progression.

• The U.S. validation study of the 4Kscore test showed it improved the detection rate of high-grade cancer on biopsy compared to a clinical algorithm built on PSA, age, digital rectal exam, and prior biopsy.

• Addition of urinary TMPRSS2:ERG to other risk models significantly increased detection of prostate cancer and high-grade disease.

• A multicenter validation trial showed that a multiplex epigenetic assay for detecting DNA-methylation events independently predicted the absence of prostate cancer in a repeat biopsy; the assay had a negative predictive value of 90%.

• A genetic risk score incorporating multiple prostate cancer risk-associated single-nucleotide polymorphisms was independently associated with prostate cancer and high-grade disease.

• Studies investigating cell cycle progression score reported associations with biochemical recurrence, metastatic disease, and disease-specific mortality.

• A physician-led quality improvement collaborative in Michigan found a 30-day hospital admission rate of 1% in a series of 3,911 prostate biopsies, of which 92% were for post-biopsy infection. The infection rate was 0.9% when the treating physician used antibiotic prophylaxis per AUA guidelines and 3.8% for non-concordant physicians.

• In a study of an active surveillance cohort, 24% of rectal swab cultures obtained prior to repeat prostate biopsy were positive for fluoroquinolone-resistant bacteria; diabetes was a risk factor for resistance.

• In a study including 1,012 men, use of magnetic resonance imaging (MRI)/ultrasound fusion-guided biopsy with 12-core biopsy led to more frequent upgrading to high-grade disease than 12-core biopsy alone, especially among men with PSA >10 ng/mL; setting a PSA threshold of 5.4 ng/mL resulted in capturing 95% of upgraded cancers and would potentially have avoided 36% of MRIs.

Next: Multiparametric MRI, metformin use

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• Non-visible tumor on multiparametric MRI does not predict low-risk disease; in a group of 177 men with nonvisible tumor who underwent radical prostatectomy (RP), 28% had pathologic upgrading and 57% had a high tumor volume (>0.5 cc).

• A study correlating multiparametric MRI with whole-mount pathology found the imaging technique missed 26% of high-grade lesions.

• The finding of an 18% discordance rate between the nodule with the largest tumor volume versus the lesion with the highest Gleason score/stage adds to evidence that prostate cancer is a multifocal disease and indicates that nondominant lesions that are high grade may have potential for metastasis.

• In epidemiologic studies, metformin use was associated with a decreased risk of prostate cancer and statin use was associated with a decreased risk of prostate cancer-specific death; while the risk of biochemical recurrence after prostatectomy was higher among patients with diabetes than patients without diabetes (31% vs. 13%), it was reduced to only 15% among men using a statin and metformin.

• Two large series of RP patients found Gleason grade 3 tumors had limited metastatic risk.

• One study provided an updated timeline on outcomes for men with intermediate- and high-risk disease; with median follow-up of 10 years, median time to BCR was 3 years, median time from BCR to metastasis was 3 years, and median time from metastasis to death was 4 years.

• In men with high-risk prostate cancer who underwent RP, the cancer-specific mortality rate was significantly higher for those with a BCR time <36 months versus >36 months (19% vs. 4%).

• In a study of men with pathologic node-positive disease at RP, 15% developed visceral/bone metastases at a median of 32 months post surgery. Tumor burden at RP was associated with the risk of metastasis and time to onset. Despite lymph node positivity, the 10-year cancer-specific survival rate was 70%.

Next: PREVAIL results, studies of HIFU, sipuleucel-T

• Two studies reported that African-American race was associated with increased risk of higher grade disease at RP, suggesting there may be a need for more stringent criteria for African-American men to be candidates for active surveillance.

• A study comparing matched groups of patients treated by high-intensity focused ultrasound (HIFU) and RP found the HIFU group had a higher 7-year rate of salvage external beam radiation therapy (38% vs. 22%), but found no difference between groups in need for palliative androgen deprivation therapy (ADT); a second study comparing intermediate-risk HIFU-treated patients with a matched group of radiation-treated patients found the rate of palliative ADT was lower in the HIFU group (15% vs. 42%).

• Results of the phase III PREVAIL trial showed enzalutamide (XTANDI) started after progression on ADT in chemotherapy-naïve men delayed disease progression, risk of death, and time to chemotherapy compared to placebo.

• Sipuleucel-T (Provenge)-induced IgG responses against PSA correlate with overall survival.

• Trained dogs detected prostate volatile organic compounds in urinary samples with nearly 100% accuracy.UT

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