A nanotechnology PSA assay shows potential for identifying prostate cancer patients at increased risk of recurrence after radical prostatectomy.
Chicago-A nanotechnology PSA assay shows potential for identifying prostate cancer patients at increased risk of recurrence after radical prostatectomy, data from a preliminary study indicate.
Higher levels of nanoPSA were associated with adverse pathology and subsequent salvage therapy. However, men who had adverse pathology and received immediate adjuvant radiation therapy had lower nanoPSA levels.
Patients who consistently had nanoPSA values less than 17 pg/mL had a near-100% probability of cure, researchers reported at the AUA annual meeting in San Francisco.
Currently for research use only, the nanotechnology PSA assay (Verisens PSA, Nanosphere, Inc.) has a 300-fold greater sensitivity for PSA compared with conventional PSA tests. The assay has a lower limit of detection of 0.5 pg/mL, equivalent to 0.0005 ng/mL.
One potential use of the nanoPSA test would be to identify men who have a high risk of recurrence after definitive surgery for prostate cancer. To illustrate the use, Dr. Zhao described a clinical scenario wherein a patient has unfavorable pathology after radical prostatectomy but an undetectable PSA value of <0.1 ng/mL by a conventional assay.
"How confident can the surgeon be that the patient is cured?" Dr. Zhao asked. "Which patients would benefit from adjuvant radiotherapy? If observation is elected, which patients would benefit from earlier salvage therapy?"
The benefits of radiation therapy in prostate cancer depend in part on the timing of therapy. For example, salvage radiotherapy has been shown to be beneficial if administered less than 2 years after recurrence in patients who have a PSA doubling time <6 months (JAMA 2008; 299:2760-9). Three randomized clinical trials have shown that adjuvant radiation therapy improves biochemical-free survival. Yet not all patients should receive radiation therapy after radical prostatectomy, Dr. Zhao noted.
Assay could prevent unnecessary radiation
A more sensitive method to detect PSA would enhance clinicians' ability to define cure, help avoid unnecessary adjuvant radiation therapy, and lead to earlier detection of recurrence. Investigators at Northwestern have developed a nanotechnology-based PSA assay that has shown potential for meeting all three of those needs, Dr. Zhao explained.
A small clinical evaluation of a first-generation nanoPSA test showed potential for risk-stratifying patients after prostatectomy. Patients who had consistently low levels of PSA over time did not recur. Among patients who had an increase in PSA levels at some point after prostatectomy, most eventually had disease recurrence (Proc Natl Acad Sci 2009; 106:18437-42).
Dr. Zhao presented results from a study involving a second-generation nanoPSA assay. Investigators used the assay on archived serum samples from 415 men who had undergone radical prostatectomy and had PSA values <0.1 ng/mL by conventional PSA assays. The study population comprised 153 men who had been followed for =10 years and 262 men who were followed for 5 to 9 years.
Investigators compared nanoPSA values associated with favorable and unfavorable disease characteristics. Among the men followed for 9 years or less, 66 had recurrences, which were associated with a median PSA value of 2.3 ng/mL and a range of 0 to 39.4 ng/mL. Of the men followed for at least 10 years, 87 had disease recurrence, associated with a median PSA value of 3.8 ng/mL and a range of 0 to 57.5 ng/mL.
The investigators chose the 90th percentile of nanoPSA values to define recurrence. That value turned out to be 17 pg/mL. Men whose initial nanoPSA value was ≥17 pg/mL were significantly more likely to have positive surgical margins (21% vs. 9%, p=.04) and to receive salvage therapy (46% vs 4%, p<.01).
Patients with nanoPSA values in the 90th percentile also had a trend toward more T2 disease (18% vs. 12%) and more Gleason ≥7 (55% vs. 40%).
The study population could be stratified into three groups: men with nanoPSA values persistently <17 pg/mL, values >17 pg/mL but not persistently rising, and values >17 pg/mL and persistently rising.
The first group comprised men who did not have recurrent disease. The second group consisted of men who had a low risk of recurrence and could be followed until nanoPSA values began to rise, at which point salvage therapy might be discussed. The third group comprised men with a high risk of recurrence and who might benefit from immediate adjuvant radiation therapy.
The nanoPSA assay was developed by co-authors Chad Mirkin, PhD, and Shad Thaxton, MD, PhD. Dr. Catalona and several of the study's co-authors have a financial or other relationship with Nanosphere.