ESOU 2019: Best of Uro-Oncology 2018 - Prostate Cancer

Prague, Czech Republic (UroToday.com) In this session, Dr. Michiel Sedelaar presents his “Best of Prostate Cancer” 2018 selections. He notes that there were over 10,000 manuscripts this past year, and many may have an impact on clinical management. Yet, he has chosen to highlight 4 that will likely be “game-changers” and warrant further attention. They cover two specific areas: diagnostics of prostate cancer and treatment of metastatic prostate cancer.

Diagnostics
  1. PRECISION study by Kasivisvanathan et al.1
In this study, the authors randomized 500 men with clinical suspicion of PCa to either MRI (with or without biopsy, depending on results) (TBx) to standard 10-12 core TRUS guided biopsy (SBx).
  • 28% of the MRI group had no abnormalities on MRI so did not receive a biopsy (which was a criticism of the study)
  • Clinically significant PCa – MRI group identified 38% while the SBx arm identified 26%
  • Clinically insignificant PCa – MRI group identified 13% less than the SBx group (9 vs. 22%)
  • He did note that patients with PIRADS 3 lesions (which were targeted), had a very low yield – 67% were negative, only 12% were csPCa
  • Based on this authors note that 28% of patients could have avoided biopsy – and those that received one would only get 4 cores, less pain, fewer risks
However, it should be noted that the NPV for csPCa of the MRI was only 76% - so approximately 1/4 may harbor some pattern 4 disease.

His summary of the trial is here:
UroToday ESOU19 PRECISION study Kasivisvanathan 1

  1. 4M Study by van der Leest et al.2 – of note, Dr. Sedelaar is one of the co-authors on this study.
In this study, over a 2 year period at 4 centers, 699 men underwent mpMRI, TRUS Bx (12-core) and targeted biopsy for each PIRADS 3-5 lesion.

Findings:

  • mpMRI detected 25% of csPCA and 14% of ciPCa
  • TRUS Bx alone detected 23% of csPCa, but 25% of ciPCa
  • MRI pathway would have avoided 49% of biopsies in patients, and reduced number of biopsies by 89%
    • In the 49% that would have avoided biopsy, at 1 year only 4% were found to have csPCa
  • The full flow diagram of patients is below:

UroToday ESOU19 van der Leest et al

He notes that, in contrast to the first study, only 6% of the mpMRI’s had PIRADS 3 lesions – so their experienced radiologists were better and confidently calling lesions either PIRADS 1-2 or 4-5.

Based on these results, the authors conclude that upfront mpMRI will yield higher csPCa yield and lower ciPCa yield. The experience of the radiologist is key to the success.

Putting the two together, his take-home message was: 

UroToday ESOU19 precision and 4m 1

mpMRI should be considered upfront for patients, but usually when done at experienced centers and in patients with high risk of PCa. Otherwise, it would be cost and time prohibitive.

Therapeutics in metastatic PCa: Role of radiation therapy

  1. HORRAD trial by Boeve et al.3

In this very important multicenter RCT completed between 2004-2014, 432 patients with mPCa were randomized to either ADT (standard of care at the time) or ADT+radiation to the primary tumor. Radiotherapy was 70 Gy in 30 fractions or 59 Gray in 19 fractions.

Findings:

  1. There was no difference in OS in both groups (43 months vs. 45 months)
  2. There was no difference in time to PSA progression in both groups (12 months vs. 15 months)
  3. However, it should be noted that this patient population had a very high volume metastatic burden – Most were Gleason 8-9, >50% had 5+ bone mets, and 60% were cT3
  4. On subgroup analysis, there was evidence that men with <5 bone mets may have some benefit (HR 0.68, CI 0.42-1.1).

Ultimately, while there were several limitations, this negative study provided some important data. Likely these patients were too far advanced to derive any benefit. But, in a subset with a smaller volume of metastatic disease, <cT2 disease and good performance status, there may be some OS benefit.

  1. STAMPEDE radiotherapy arm by Parker et al.4

Soon after, the STAMPEDE investigators released this arm of their multi-arm study, comparing men with mPCa to a standard of care (ADT +/- docetaxel) to SOC + radiotherapy (55Gy in 20 fx or 36Gy in 6 fractions). While a slightly lower dose than HORRAD, this study benefits for a planned subgroup analysis based on CHAARTED criteria of low/high volume metastatic burden.

Findings:

  1. In unselected patients (all-comers), radiotherapy did not improve OS
  2. However, in selected low-volume metastatic burden patients (<4 bone mets and all within bony pelvis), there was an OS benefit. There appeared to benefit to all the endpoints.

Putting both these studies together, here is his take-home slide:

UroToday ESOU19 HORRAD and stampede

Presented by: Michiel Sedelaar, Onco Urologist, Deputy Chief of Department, Nijmegen Area, Netherlands, Hospital & Health Care

Written by: Thenappan Chandrasekar, MD. Clinical Instructor, Thomas Jefferson University, Twitter: @tchandra_uromd, @TjuUrology, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic

References:
1. Kasivisvanathan V, et al. PRECISION Study Group Collaborators. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med. 2018 May 10;378(19):1767-1777. doi: 10.1056/NEJMoa1801993. Epub 2018 Mar 18.
2. van der Leest M, et al. Head-to-head Comparison of Transrectal Ultrasound-guided Prostate Biopsy Versus Multiparametric Prostate Resonance Imaging with Subsequent Magnetic Resonance-guided Biopsy in Biopsy-naïve Men with Elevated Prostate-specific Antigen: A Large Prospective Multicenter Clinical Study. Eur Urol. 2018 Nov 23. pii: S0302-2838(18)30880-7. doi: 10.1016/j.eururo.2018.11.023. [Epub ahead of print]
3. Boevé LMS, et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol. 2018 Sep 25. pii: S0302-2838(18)30658-4. doi: 10.1016/j.eururo.2018.09.008. [Epub ahead of print]
4. Parker CC, et al. Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018 Dec 1;392(10162):2353-2366. doi: 10.1016/S0140-6736(18)32486-3. Epub 2018 Oct 21.


Further Related Content:
Best of Uro-Oncology 2018: Penile and Testis Cancer
Best of Uro-Oncology 2018: Renal Cancer
Best of Uro-Oncology 2018 – Urothelial Cancer

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