ASCO GU 2018: Best of Journals: Prostate - Surgery

San Francisco, CA (UroToday.com) Dr. Cooperberg presented key publications in prostate cancer in the past year. From his prior presentation in 2016, he had hoped for more development in three area: more treatment (surgery) for high-risk disease, less (or no) treatment for low risk disease, and smarter screening (based on the above two points). While we have made strides in the right direction, we still have work to go.

The three themes for his current talk are as follows:

1) Screening is (finally) getting smarter
2) MRI has changed absolutely everything about prostate cancer – but not really?
3) Progress towards personalization (including intensification for high-risk disease)

The key points from the talks and appropriate references are below.

Screening

1. PLCO1 final result – 15 years is still not fully adequate. Final lessons – this was a study on organized screening vs. opportunistic screening. There was no benefit to organized screening. However, a subgroup analysis taking into account the lead time bias of the opportunistic screening, there is compatible evidence that screening reduces mortality.2
2. Screening is better late than never – Johnston et al3 found that men who were diagnosed with advanced disease in the screening process for ProtecT still did better than men who were never screened.
3. Targeted screening efforts work, especially in younger patients with family history or African heritage4

MRI and prostate cancer

1. MRI studies have skyrocketed in the past few years – 600-700 studies per year in the past 3 years
2. PROMIS study5 – well-designed study comparing mpMRI and TRUS Bx in the diagnosis of prostate cancer. While they conclude that mpMRI may be used as a triage test to determine need for biopsy, Dr. Cooperberg pointed out that their primary endpoint of identifying clinically significant prostate cancer excluded Gleason 3+4=7 PCa. If those are included, the NPV is only 76%. We now know that some Gleason 3+4=7 PCa represents true disease. Hence, probably too early to write off TRUS Bx.
3. High degree of variability in mpMRI reports, even in high-volume centers – two nice papers demonstrate this variability in high-volume centers.6,7
4. MRI, like other biomarkers, is an increasingly valuable adjunct to standard assessment

AS in the real-world

1. AS utilization varies significantly still in the US and Europe, even within practices at a physician-level8

Neoadjuvant therapy prior to localized definitive therapy

1. No answers yet!
2. Negative study using enzalutamide + ADT prior to RP9
3. Further studies ongoing – likely that chemotherapy may have a better response


Genomic testing

1. PAM50 classified and introduction of basal/luminal subtyping to PCa10 – great study. Basal and Luminal A subtypes had much better PCa-specific survival compared to Luminal-B subtype, even when accounting for clinical-pathologic characteristics.
2. Significant genomic diversity in all stages of PCa, even in early Gleason 6 disease11 

Final conclusions and future goals:

1. Better consensus and cooperation with primary care physicians re: smarter screening
2. Optimization and tailoring of AS protocols
3. More and better trials combining local and systemic therapies for high-risk disease, ideally based on individual tumor biology.


Presented by: Matthew R. Cooperberg, MD, MPH University of California, San Francisco

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto | @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

References:

1. Pinsky PF, Prorok PC, Yu K, Kramer BS, Black A, Gohagan JK, Crawford ED, Grubb RL, Andriole GL. Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years. Cancer. 2017 Feb 15;123(4):592-599. doi: 10.1002/cncr.30474. Epub 2016 Dec 1.

2. Tsodikov A, Gulati R, Heijnsdijk EAM, Pinsky PF, Moss SM, Qiu S, de Carvalho TM, Hugosson J, Berg CD, Auvinen A, Andriole GL, Roobol MJ, Crawford ED, Nelen V, Kwiatkowski M, Zappa M, Luján M, Villers A, Feuer EJ, de Koning HJ, Mariotto AB, Etzioni R. Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials. Ann Intern Med. 2017 Oct 3;167(7):449-455. doi: 10.7326/M16-2586. Epub 2017 Sep 5.

3. Johnston TJ et al, ProtecT study group. Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial. Eur Urol. 2017 Mar;71(3):381-388. doi: 10.1016/j.eururo.2016.09.040. Epub 2016 Oct 6.

4. Gulati R, Cheng HH, Lange PH, Nelson PS, Etzioni R. Screening Men at Increased Risk for Prostate Cancer Diagnosis: Model Estimates of Benefits and Harms. Cancer Epidemiol Biomarkers Prev. 2017 Feb;26(2):222-227. doi: 10.1158/1055-9965.EPI-16-0434. Epub 2016 Oct 14

5. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham AP, Oldroyd R, Parker C, Emberton M; PROMIS study group. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017 Feb 25;389(10071):815-822. doi: 10.1016/S0140-6736(16)32401-1. Epub 2017 Jan 20.

6. Sonn GA, Fan RE, Ghanouni P, Wang NN, Brooks JD, Loening AM, Daniel BL, To'o KJ, Thong AE, Leppert JT. Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists. Eur Urol Focus. 2017 Dec 6. pii: S2405-4569(17)30266-3. doi: 10.1016/j.euf.2017.11.010. [Epub ahead of print]

7. Greer MD. Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: A multireader study. J Magn Reson Imaging. 2017 Feb;45(2):579-585. doi: 10.1002/jmri.25372. Epub 2016 Jul 8. Auffenberg GB et al. Practice- vs Physician-Level Variation in Use of Active Surveillance for Men With Low-Risk Prostate Cancer: Implications for Collaborative Quality Improvement. JAMA Surg. 2017 Oct 1;152(10):978-980. doi: 10.1001/jamasurg.2017.1586.

9. Montgomery B, et al. Neoadjuvant Enzalutamide Prior to Prostatectomy. Clin Cancer Res. 2017 May 1;23(9):2169-2176. doi: 10.1158/1078-0432.CCR-16-1357. Epub 2016 Nov 9.

10. Zhao SG et al. Associations of Luminal and Basal Subtyping of Prostate Cancer With Prognosis and Response to Androgen Deprivation Therapy.  JAMA Oncol. 2017 Dec 1;3(12):1663-1672. doi: 10.1001/jamaoncol.2017.0751.

10. Fraser M, Boutros PC, et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature. 2017 Jan 19;541(7637):359-364. doi: 10.1038/nature20788. Epub 2017 Jan 9.
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