Several reports have been published on the steady decline in the incidence of prostate cancer diagnosis over the last 4 years which most reference this to be direct due to the 2012 USPSTF recommendation against PSA screening. It is well known that the evidence used to for the USPSTF recommendation against prostate cancer screening came from the results of the PLCO trial. In a report by Roobol et al, the high degree of PSA testing contamination in the PLCO trial was further studied and validated showing that approximately 90% of patients in the control arm underwent some form of PSA screening during the trial. This report has been used to question the validity of the PLCO trial and its results, which are more representative a screening vs. more intensive screening trial.
In regards to prostate cancer diagnosis the PROMIS trial was published which assessed the use of multiparametric MRI (MP-MRI) of the prostate for the primary diagnosis of prostate cancer in men presenting an elevated PSA. In the trial MP-MRI was compared to transperineal mapping biopsy (TMP-biopsy) and TRUS-Biopsy in regards to identifying clinically significant prostate cancer defined as Gleason ≥ 4+3. The study showed that MP-MRI outperformed both TMP and TRUS biopsies at identifying clinically significant prostate cancer and MP-MRI as a triage test could safe identify at up to 25% of men who could avoid an unnecessary biopsy.
This year we also saw a reclassification of prostate cancer in Gleason score into risk groups: 1. Gleason 3+3, 2. Gleason 3+4, 3. Gleason 4+3 and 5. Gleason ≥ 8. This new classification has been shown to have good reliability in regards to cancer outcomes and it has allowed for easier patient counseling. The introduction of PI-RADS 2.0 has also helped further standardized the reporting of MP-MRI results which have helped in the generalization of prostate MRI data. We also saw the introduction of the metastatic reporting system called the MET-RADS-P, which we hope will sever to standardized the reporting of the several new imaging techniques being developed for prostate cancer.
There is had been great excitement in the use of focal therapy for the treatment of low risk to intermediate risk prostate cancer. The French Urological association published their results in the use of HIFU for focal treatment of prostate cancer. In the trial 110 men were treated with hemi-gland HIFU. Following HIFU on planned follow-up biopsy 19% patients were noted to have cancer in the contralateral side, with 12% showing persistent cancer. Of all the cancers detected on repeat biopsies 12% were noted to be clinically significant. The PCM301 study also reported their results on the use of Padeliporfin vascular targeted photodynamic (VTP) therapy focal therapy vs. active surveillance. 413 patients from 47 European centers were randomized in the study. Inclusion criteria for the study was as follows: clinical stage T2b or below, PSA ≤ 10 ng/mL, Gleason 3 pattern only, and a prostate volume of 25-70ccc. The main study outcome was treatment failure at 24-months along the absence of active cancer. At 24 months 28% of patients in the VTP group were found to have disease progression compared to 58% in the active surveillance group. The high progression rate in the active surveillance group has raised some questions on the validity of study.
One the most controversial publication this year was the systematic review and meta-analaysis by Wallis et al, comparing the outcomes of surgery vs. radiation therapy for the treatment of clinically localized prostate cancer. The study showed that surgery was favored in regards to overall mortality and cancer specific mortality which goes against the results of the ProTect trial which showed no difference in the survival outcomes in those treated with surgery or radiotherapy. Another controversial publication was he randomized controlled trial assessing the early outcomes of robotic assisted radical prostatectomy (RALP) vs. open retro-pubic prostatectomy (RP). The study recruited 326 patients of which 151 underwent open RP vs. 157 undergoing RALP. There was no difference in functional outcomes or pathological outcomes between the two procedures.
In regards to radiation therapy it has been the year of hypofractionation were several reports addressing its safety both functionally and oncologically. The HYPRO study which included 820 Dutch men showed no difference in relapse-free survival in those receiving 64Gy in 19 fractions vs. 78Gy in 39 fractions. There were also two seminal reports published (GETUG-AFU 16 and RTOG 9601) regarding the superior oncological outcomes (OS and PFS) associated with the use of ADT in conjunction with salvage radiation therapy in patients with biochemical recurrence following RP.
One of the most significant breakthroughs in the treatment of metastatic prostate cancer was the improved survival associated with the addition of Docetaxel to ADT in the treatment of hormone sensitive metastatic prostate cancer. The results reported by CHAARTED, GETUG 15 STAMPEDE trial showed that docetaxel improved failure free survival (HR 0.64, p< 0.001) with a reduction in absolute 4 year failure rate of 16%.
Lastly improvements in nuclear medicine targeted imaging have allowed for better patient staging and modifications of treatment plans. Most exciting data comes from the use of Ga-PSMA PET CT which in have allowed the detection of micro-metastatic disease in up 51% of patients. In a study published this year the pre-treatment use of PSMA PET-scans aided in the filed expansion leading to improved post EBRT PSA nadir levels following EBRT.
James Catto, BM, ChB, PhD, FRSC, University of Sheffield
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