One of the most important publications of the year was the study by Dr. Welch et al, assessing the temporal trends of metastatic prostate cancer as it compared to breast cancer. The study showed that following the institution of PSA screening the incidence of metastatic prostate cancer decreased sharply while the institution of mamamography screening did not seem to have much of an effect in the rates of metastatic breast cancer. This phenomenon is likely due to differing cancer dynamics between the two organs sites. Prostate cancer likely follows a more Halstedian model of cancer progression (cancer foci → lymph-nodes → distant metastasis) in which early screening will prevent further progression. In contrast, breast cancer likely follows a different path, a Fisher cancer model, in which metastatic disease has already occur at the time of diagnosis.
Several publications this year attempted to assess the impact of the USPSTF 2012 recommendation against prostate cancer screening. Report by Halpern et al, showed that since 2012 prostate biopsy volume has decreased by 29%, with a 16% decrease in radical prostatectomy rates. In a manuscript by the speaker the incidence of metastatic disease at diagnosis was evaluated using SEER data, showing a sharp increase in the incidence of metastatic disease in men > 75 years which is likely a result of the 2008 USPSTF recommendation against screening in men 75 year or older. It is well known that one of the evidence pillars used to for the USPSTF recommendation against prostate cancer screening came from the results of the PLCO trial. A report by Shoag et al, showed a high degree of PSA testing in the control arm of the trial, with approximately 90% of men in the control arm receiving some form of PSA screening. This high degree of contamination in the control arm has questioned validity of the PLCO trial and its results, which are more representative a screening vs. more intensive screening trial.
In an important report by Preston et al, looked at PSA cut off points at different age time points to assess the risk of developing lethal prostate cancer. The study showed that 1 of 7 men with a PSA > 3 ng/mL at 55-59 years and 1 of 12 with a PSA > 2.1 ng/mL at 50-54 years experiences lethal prostate cancer. In contrast, men with PSA below the median at the age of 60 (< 1.0 ng/mL) were very unlikely to develop lethal prostate cancer and cessation of screening should be considered.
In regards to the use of MRI the PROMIS trial was reported this year which assessed the use of multiparamatetic MRI (mp-MRI) for the diagnosis of prostate cancer in men with elevated PSA. The trial aimed to compare mpMRI to TRUS biopsy for the diagnosis of prostate cancer using transperineal mapping template biopsy as the standard comparison due to its high rcancer detection sensitivity (>95%). The results showed mpMRI had higher sensitivity for clinical significant prostate cancer, defined as Gleason ≥ 4+3, but TRUS biopsy showed higher specificity and a higher positive predictive value. The authors then modeled MRI as a triage test instead of TRUS biopsy, a suspicious MRI being defined as PIRADS ≥ 3. Using this mpMRI as the main screening tool the authors went to conclude that 27% of men would avoid TRUS biopsy with an 18% increase in the detection of clinically significant cancers. TRUS biopsy will still be required due to the lower specificity and positive predictive value of MRI.
In the realm of active surveillance the results of the PRIAS study was reported which included over 5000 men from 18 different countries managed under an active surveillance (AS) program with 10 year follow-up. The authors, performed a multivariate analysis to assess clinical and pathological characteristics associated with progression. The study showed that PSA dynamics had minimal impact on disease progression; whereas, Gleason upgrading or clinical updating (DRE or MRI) were more predictive to disease progression. The authors conclude that PSA kinetics or doubling time should not be used as a criteria for switching to active treatment but should be used instead for more comprehensive screening with TRUS biopsy or mpMRI.
Advances in cancer imaging by mpMRI has open the door for the use of focal therapy in patients with unifocal prostate cancer. High frequency focus ultrasound (HIFU) was recently approved by the FDA for prostate gland ablation, which has led to an increased in the use of the technology for focal treatment of prostate cancer. Dr. Hu, cautions the audience in the fast adoption of this technology as long term data is lacking in regards to clinical outcomes and the technology may ultimately lead to an increase in overall prostate cancer care cost due to the necessity for multiple and salvage treatments.
Speaker: Jim C. Hu, MD, MPH, Weill Cornell Medical College
Written By: Andres F. Correa, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA