By: Dan Sperling, MD
Gambling at a casino is a recreational choice, and savvy gamers know that the odds always favor the house. Still, gamblers try to play probabilities to increase their chances of winning. No one, however, wants to gamble with prostate cancer (PCa). Every effort by doctor and patient should go into obtaining as accurate a diagnosis as possible in order to determine the best treatment options including active surveillance. Unfortunately, the clinical tools currently available cannot render a PCa diagnosis with 100% certainty, so there is always some element of risk calculation in order to make treatment decisions.
For decades, physicians relied on something called a nomogram to guide their advice to patients. A nomogram is a set of scales that can be used to calculate an unknown value, and when adapted for medicine, they act as a statistical modeling tool. The classic nomogram used to predict the chances that PCa has left the gland at the time of treatment is called the Partin tables. The tables are named for Alan W. Partin, an expert in evaluating and predicting the prognosis for the disease, because they are derived from his research. Originally, the “scales” on which risk predictions were made includes three clinical factors: total PSA, Gleason grade, and clinical stage or digital rectal exam results. A urologist would literally consult pages of printed tables to correlate all three, and find the percent odds (probability) that “the horse was out of the barn,” as patients used to say. Today, the tables have been repeatedly updated as new clinical information becomes available. Computers have now replaced printed pages, and patients can use online risk calculators such as the New Partin Nomogram 2011 found at the Johns Hopkins/Brady Urological Institute (http://urology.jhu.edu/support/partinTables.php), which can offer the chances of organ-confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node invasion.
In addition to calculators based on the Partin tables, other experts and researchers have continued to develop alternative risk calculators. The search for an ideal statistical tool is important, because bringing a high level of confidence to calculated risk levels has implications for reducing unnecessary interventions like repeat biopsies during active surveillance and overly aggressive whole-gland treatments for insignificant PCa. Some of these, like risk calculator developed from results of the European Randomized Study of Screening for Prostate Cancer or the Prostate Cancer Prevention Trial show some promise for predicting significant PCa, but were generally lackluster.[i]
Two papers published this year (2015) offer optimistic results of incorporating information from multiparametric MRI (mpMRI) into PCa nomograms. The first report was written by a team from the Urologic Oncology Branch of the National Cancer Institute/National Institutes of Health.[ii] Their goal was to create a way to decrease interventions in active surveillance patients. According to the authors,
PURPOSE: Multiparametric magnetic resonance imaging may be beneficial in the search for rational ways to decrease prostate cancer intervention in patients on active surveillance. To do so, the evaluated the accuracy of a previously published nomogram used with patients before confirmatory biopsy. They retrospectively used the nomogram with the records of 85 patients who were candidates for active surveillance based on initial biopsy, and who also had 3T mpMRI following by fusion guided biopsy. Using the nomogram low, medium and high risk cutoff levels, they determined how many biopsies could be avoided based on mpMRI results alone. They “…assessed the performance of the multiparametric magnetic resonance imaging active surveillance nomogram based on a decision to perform biopsy at various nomogram generated probabilities.” They determined that as many as 68% of their active surveillance cohort could be spared repeat biopsy. In their conclusion, they describe the potential for patient and physician to make repeat biopsy decisions based on the calculated risk with the addition of mpMRI information.
The second study is from a team at Cedars-Sinai Medical Center in Los Angeles, who compared the accuracy of mpMRI with the Partin tables as well as the Memorial Sloan Kettering (MSK) nomogram for predicting extracapsular extension (ECE).[iii] Their work involved a retrospective review of 112 patients who had 3T mpMRI before radical prostatectomy, from which specimens the incidence of ECE was determined by pathology evaluation (histopathology). They discovered that mpMRI had identified 33 patients (29%) with ECE, but 26 (23%) were determined to have ECE on final pathology. When the MRI results were integrated with the Partin tables and the MSK nomogram, they strengthened the accuracy of the two nomograms’ predictions of ECE, noting that “Within the typical range of risks for ECE provided by the clinical nomograms (i.e., 15%-40%), MRI was useful for predicting pathologic ECE.”
The accuracy of PCa risk calculations will continue to evolve. Adding image-based detection both enhances and refines the ability of nomograms to provide better probability projections, enabling physician and patient to make informed choices regarding PCa interventions. The potential for lessening the number of procedures, or reducing the aggression level of treatments, will improve patient quality of life while saving medical dollars.
[i] Poyet C, Nieboer D, Bhindi B, Kulkarni G et al. Prostate cancer risk prediction using the novel versions of the ERSPC and PCPT risk calculators: Independent validation and comparison in a contemporary European cohort. BJU Int. 2015 Aug 31. doi: 10.1111/bju.13314. [Epub ahead of print]
[ii] Siddiqui MM, Truong H, Rais-Bahrami S et al. Clinical implications of a multiparametric MRI based nomogram applied to prostate cancer active surveillance. J Urol. 2015 Jan 26. pii: S0022-5347(15)00178-0.
[iii] Feng TS, Sharif-Afhsar AR, Wu J, Li Q et al. Multiparametric MRI Improves Accuracy of Clinical Nomograms for Predicting Extracapsular Extension of Prostate Cancer. Urology. 2015 Aug;86(2):332-7.