ESMO 2018: Update on Diagnosis and Treatment of Localized Prostate Cancer

Munich, Germany (UroToday.com) Dr. Mark Emberton, gave a discussion on the diagnosis and treatment of localized prostate cancer. According to Dr. Emberton, a renowned urologist, based in London, UK, the most important event in localized prostate cancer in the last decade, in terms of early disease risk stratification, is the introduction of imaging into the diagnostic pathway to confer location. The incorporation of imaging in the diagnostic process has provided us with a vast amount of information that we did not have before. This includes location, volume, multiplicity, and probability.

The first attempt at prostate MRI had occurred more than 30 years ago in 19821, but the resolution of MRI at that time was not able to provide accurate and user-friendly information. With the improvement of technology, the resolution of MRI used today is quite exceptional, providing us with accurate and usable imaging. Correlating the results of prostate MRI with the pathologic results of radical prostatectomy has enabled us to learn the attributes of prostate MRI, demonstrating a sensitivity of 90%, specificity of 88%, pa positive predictive value of 77%, and negative predictive value of 95% for a tumor measuring 0.5 cc on prostate MRI.2

In 2013 a multidisciplinary team met and formed the START consortium, creating the standards for reporting MRI targeted biopsy, and formulating a new language for reporting prostate MRI results.  There have been many studies attempting to explore the role of prostate MRI before a prostate biopsy, with a large proportion of them demonstrating positive results (Figure 1).  In 2016 the first prospective study was published comparing MRI imaging vs. standard transrectal ultrasound-guided (TRUS) biopsy.3 In this study, all patients were biopsy naïve, with a PSA of less than 15 ng/dl, with a normal digital rectal examination. Patients were randomized to either a regular TRUS biopsy or to a prostate MRI first. A total of 223 patients were randomized. The results demonstrated that the overall and clinically significant cancer detection rates were 51% and 44% vs. 30% and 18% in the MRI and standard TRUS arms, respectively.

In the PROMIS study, the diagnostic accuracy of multiparametric MRI and TRUS were compared, using a transperineal template biopsy for confirmation.4 Three definitions of the clinically meaningful endpoints within PROMIS include:

  1. Primary – Any dominant Gleason pattern 4 and/or 6 mm or more of any cancer
  2. Secondary 1 – Any secondary Gleason pattern 4 and/or 4 mm or more of any cancer
  3. Secondary 2 – Any Gleason pattern 4
The results in PROMIS demonstrated that any cancer was found in 71% of patients, while clinically significant cancer was diagnosed in 40% of patients. The study showed that MRI had 93% sensitivity. Standard TRUS biopsy misses all Gleason patterns of cancer in an equal manner, while MRI misses mainly Gleason 3 pattern. The association of PIRADS score and cancer status in the MRI arm of the PRECISION trial5, published in the New England Journal of Medicine in 2018, is shown in figure 2. This trial prospectively randomized patients and compared standard TRUS biopsy to MRI targeted biopsy, only if the MRI was positive.
UroToday ESMO2018 Prostate MRI studies
Figure 1 – Prostate MRI studies:
UroToday ESMO2018 Association between PIRADS score and cancer status in the MRI arm of the PRECISION trial
Figure 2 – Association between PIRADS score and cancer status in the MRI arm of the PRECISION trial5:

According to the PRECISION study, an MRI targeted biopsy strategy resulted in fewer men undergoing biopsy, fewer needle deployments, more clinically significant cancer diagnosed (38% vs. 26%), less clinically insignificant cancer detected (9% vs. 22%), and fewer 30-day patient-reported complications. The PRECISION trial demonstrated that in biopsy naïve men, with a clinical suspicion of prostate cancer, prebiopsy MRI and MRI targeted biopsy in a sub group of men appeared to be a superior strategy when compared to the existing standard of care.

Imaging has also helped us plan treatment with radiotherapy in a more accurate way. Moreover, it enables to pinpoint the required dissection in radical prostatectomy and understand where a higher risk of extraprostatic disease might exist and to deal with it appropriately. Furthermore, MRI imaging is allowing focal therapy for prostate cancer to be more accurate and has improved its outcomes.

Dr. Emberton concluded his talk, providing some information on focal therapy of prostate cancer. In a multicenter study of 5-years outcomes following focal therapy in treating clinically significant localized prostate cancer, that was recently published6, the results seemed very encouraging. In this study, 72% of the patients had Gleason 3+4 disease, and 87% of the patients were either intermediate or high-risk patients according to the D’Amico risk classification. Although the follow-up for prostate cancer was relatively short, the 5-year failure-free survival rates were 88% for intermediate-risk disease and 87% for Gleason 7 disease. The greatest advantage of focal therapy according to Dr. Emberton, is the low percentage of adverse events, compared to that encountered in definitive radical treatment.


Presented by: Mark Emberton, Professor of Interventional Oncology, Division of Surgery and Interventional ScienceUniversity College Hospital, London, Great Britain, UCL

References:
1. Stein and SMITH BJUI 1982
2. Villers A et al. J Urol 2006
3. Porpiglia F et al. Eur Urol 2016
4. Ahmed et al. LANCET 2017
5. Kasivisvanathan V et al. NEJM 2018
6. Guillaumier S et al. Eur Urol 2018

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 2018 European Society for Medical Oncology Congress (#ESMO18), October 19-23,  2018, Munich Germany
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