ESOU 2019: The best of 2018 uro-oncology

Prague, Czech Republic (UroToday.com) During this session, Dr. Michiel Sedelaar presents his "Best of Prostate Cancer" selections 2018. He notes that there were more than 10,000 manuscripts during last year and that many could have an impact on clinical management. Still, he chose to highlight 4 that will likely be "game changers" and deserve more attention. They cover two specific areas: the diagnosis of prostate cancer and the 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 prostate cancer either by MRI (with or without biopsy, based on the results) (TBx) or by standard 10-12 nuclei guided biopsy by TRUS ( SBx).

• 28% of the MRI group had no abnormalities on MRI, so they did not undergo a biopsy (which was a criticism of the study).
• The clinically significant PCa – MRI group identified 38%, while the SBx arm identified 26%.
• Clinically insignificant PCa-MRI group identified 13% less than SBx group (9 versus 22%)
• He noted that patients with PIRADS 3 lesions (who were targeted) had a very poor performance: 67% were negative, only 12% had csPCa.
• Based on this authors' note, 28% of patients could have avoided the biopsy – and those who received one would have only 4 cores, less pain, less risk.

However, it should be noted that the NPV for the CPPCa of MRI was only 76% – so about 1/4 can harbor a type 4 disease.

His summary of the trial is here:

2. 4M study van der Leest et al.² – Note that Dr. Sedelaar is one of the co-authors of this study.

In this study, over a 2-year period in 4 centers, 699 men underwent MRI-IRM, TRUS Bx (12 cores) and a targeted biopsy for each 3-5 PIRADS lesion.

Results:

• pMRI detected 25% csPCA and 14% ciPCa
• TRUS Bx alone detected 23% csPCa, but 25% of ciPCa
• MRI would have avoided 49% of biopsies in patients and reduced the number of biopsies by 89%
  • Of the 49% who would have avoided a biopsy, at 1 year, only 4% had csPCa
• The complete patient chart is shown below:

He notes that, unlike the first study, only 6% of MRI-MRIs had PIRADS 3 lesions – so their experienced radiologists were better and called PIRADS 1-2 or 4-5 lesions with confidence.

On the basis of these results, the authors conclude that an initial mpMRI would give a higher yield of csPCa and a lower yield of ciPCa. The radiologist's experience is the key to success.

Gathering the two together, his message was:

The pMRI should be considered from the outset for patients, but usually when it is performed in experienced centers and in patients at high risk of prostate cancer. Otherwise, the cost and time would be prohibitive.

Therapeutics in metastatic bad cancer: role of radiotherapy

1. HORRAD trial by Boeve et al.³

In this very large multicenter RCT performed between 2004 and 2014, 432 patients with mPCa were randomized to receive either ADT treatment (standard treatment at the time) or ADT + treatment at the primary tumor. Radiotherapy was 70 Gy in 30 fractions or 59 Gray in 19 fractions.

Results:

1. There was no difference in SG in both groups (43 months versus 45 months)
2. There was no difference in time until PSA progression in both groups (12 months vs. 15 months)
3. However, it should be noted that this patient population had a very high metastatic burden – most were Gleason 8-9, more than 50% had more than 5 bone dishes and 60% were of the cT3 group.
4. In subgroup badysis, it has been shown that men with less than 5 bone dishes could have a benefit (HR 0.68, CI 0.42-1.1).

In the end, although there are several limitations, this negative study has provided important data. These patients were probably too advanced to make any profit. However, in a subset with a lower volume of metastatic disease, <cT2 disease, and good performance status, there may be a benefit in terms of ES.

2. The STAMPEDE radiotherapy arm from Parker et al.⁴

Shortly after, STAMPEDE investigators published this arm of their multi-arm study, comparing men with mPCa to standard therapy (ADT +/- docetaxel) to SOC + radiotherapy (55Gy in 20 fx or 36 Gy in 6 fractions). Although its dose is slightly lower than that of HORRAD, this study presents the benefits of a planned subgroup badysis based on CHAARTED criteria of metastatic load in low / high volume.

Results:

1. In unselected patients (all comers), radiotherapy did not improve SG
2. However, in some patients with low volume metastatic load (<4 bone dishes and all in the bone pool), there was a benefit to the SG. It seems that this benefits all end points.

Combining these two studies, here is his slide to take away:

Presented by: Michiel Sedelaar, Onco Urologist, Deputy Department Head, Nijmegen Region, The 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 Urologic Oncology, # ESOU19, January 18-20, 2019, Prague, Czech Republic

References:
1. Kasivisvanathan V, et al. Collaborators of PRECISION study groups. Standard or MRI-targeted biopsy for the diagnosis of prostate cancer. N Engl J Med. May 10, 2018, 378 (19): 1767-1777. doi: 10.1056 / NEJMoa1801993. Epub 2018 March 18th.
2. van der Leest M, et al. Direct comparison between ultrasound-guided transrectal prostate biopsy and multiparametric resonance imaging of the prostate with subsequent magnetic resonance guided biopsy in biopsy-naive men with high prostate-specific antigen: prospective multicenter clinical trial of huge proportion. Eur Urol. Nov. 23, 2018,: S0302-2838 (18) 30880-7. doi: 10.1016 / j.eururo.2018.11.023. [Epub ahead of print]3. Boevé LMS, et al. Effect on the survival of androgen deprivation therapy alone compared with androgen deprivation therapy badociated with concomitant prostate radiotherapy in patients with metastatic primary bone prostate cancer in a prospective randomized clinical trial: HORRAD test. Eur Urol. Sep. 25, 2018: 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 researchers on the effectiveness of the drug (STAMPEDE). Primary tumor radiotherapy for newly diagnosed metastatic prostate cancer (STAMPEDE): Randomized Phase 3 controlled trial. Lancet. 2018 December 1 st; 392 (10162): 2353-2366. doi: 10.1016 / S0140-6736 (18) 32486-3. Epub 2018 October 21st.

Other related content:
Best of Uro-Oncology 2018: Penis and Testicular Cancer
Best of Uro-Oncology 2018: Kidney Cancer
Best of Uro-Oncology 2018 – Urothelial Cancer