CUA 2018: Evolving Approaches in Diagnosing Prostate Cancer: Beyond PSA

Halifax, Nova Scotia (UroToday.com) This session covered several topics in the diagnosis of prostate cancer (PC). The topics that were covered included:

  1. Usage of MRI in biopsy naïve patients
  2. MRI in the optimization of surgical outcomes – a role for nerve-sparing planning and high-risk disease
  3. Metastatic PC
Frank Bladou, MD started this session talking about the role of MRI as a triage test in biopsy naïve patients. The problem with the current standard of diagnosis of trans-rectal ultrasound (TRUS) guided biopsy is the over-detection of insignificant PC, and under-detection of clinically significant PC. According to Bladou, image targeted biopsy would improve the results of the systematic biopsy by increasing the diagnosis of clinically significant PC, decreasing the diagnosis of clinically insignificant PC, and decreasing the need for unnecessary biopsies in general. 

Currently, mpMRI in Canada is approved only after a previous negative TRUS biopsy.  Bladou thinks that we can avoid 12 core systematic biopsy and do only MRI -targeted biopsies. This is not yet recommended, but there is supporting evidence from the PROMIS study1 and the PRECISION study2. According to the PROMIS study, mpMRI can be used as a triage test before the first biopsy to allow 27% of men at risk to avoid a biopsy. MRI targeted biopsies improve detection of clinically significant cancer (18% more vs. standard TRUS biopsy). mpMRI can also reduce the over-diagnosis of clinically insignificant PC in 5% of cases. Similar findings were shown in the recently published PRECISION trial2.

Next, Freddie Hamdy, MD, discussed the topic of MRI in the optimization of surgical outcomes. He began by discussing the indications for nerve sparing. This depends on a multitude of factors, including preoperative sexual activity, disease grade and volume, serum PSA, mpMRI findings, digital rectal examination (DRE) findings, operative findings, nomogram results, and additional technology developments which are underway. 

Hamdy gave some details on the differences between the US and Europe, stating that approaches to indications and delivery of radical prostatectomy are similar on both continents. Open surgery is still offered with excellent results in high-volume centers in Europe. There is a clear trend showing a reduction in surgery for low-risk disease in both continents. The major differences between US and UK/Europe is in the speed of mpMRI uptake (the majority of UK centers now perform pre-biopsy mpMRI, and most European centers have access to PSMA-PET CT). Lastly, there is greater considerable interest in genomic markers in the US compared to Europe.

Hamdy concluded his talk by sharing his opinion on radical prostatectomy for high-risk disease. Preoperative mpMRI should definitely be done in these patients before attempting surgery, and recently, a nomogram developed to incorporate mpMRI results for prediction of extracapsular extension of PC has been published[3]. Additional factors to be taken into consideration in these high-risk patients before surgery include careful pre-operative evaluation, careful patient counseling for expectations, and we need to make sure that there are no positive margins. Extended lymphadenectomy must be performed and patients must be explained the risk of salvage/adjuvant radiation, which is highly likely in high-risk disease. Lastly, these patients need to be followed and treated with multimodality additional treatments as necessary.

Frederick Pouliot, MD, continued the discussion on the usage of imaging in high-risk PC patients. According to the AUA-ASTRO-SUO guideline recommendations cross-sectional imaging, in the form of cross-sectional abdominopelvic CT or prostate and pelvis MRI, and bone scan should be done in patients with:

  • Unfavorable intermediate-risk disease (2 or more of the following – palpable nodule on DRE, Gleason 7 disease, and PSA above 10 ng/ml)
  • High-risk disease (PSA >20 ng/ml, or grade group 4-5, or clinical stage >T3)
However, the specificity and sensitivity of the currently used bone scan for detecting bone metastasis is lower than that of Choline PET/CT (96% vs. 80% sensitivity, and 91% vs. 79% specificity). Therefore, abnormal findings on conventional imaging in the form of the bone scan will be falsely positive in 20% of patients. This leads us to use new imaging modalities in staging these patients.

Bladou gave another talk on the topic of molecular imaging of PC (Flurocholine and PSMA PET/CT). PET/CT fusion imaging is a multimodal hybrid imaging modality which delivers both anatomical and functional data at the same time. The proposed indications for PET scans in PC include:

  • Restaging of biochemically recurrent disease (PSA relapse)
  • Initial staging in high-risk patients
  • Treatment monitoring of patients with metastatic disease
Bladou gave an overview of the F-fluoromethylcholine (FCH) PET/CT. Choline is required for synthesis of cell membrane phospholipids. It is taken up avidly by PC cells and is cleared quite quickly from the blood. It is relatively easy to synthesize on cassette-based systems and inexpensive. The Jewish General hospital experience in Montreal, Canada with FCH was then presented, demonstrating a sensitivity of 84% and specificity of 65% in patients with biochemical recurrence.[4] When assessing FCH in the staging of high-risk patients, it demonstrated a sensitivity of 62-64% and specificity of 100% for both bone and lymph node metastasis. The main limitations of FCH include its limited value for T-staging at diagnosis, where mpMRI is superior. Additionally, it has poor sensitivity for N-staging in high-risk patients, and poor yield in PSA recurrence when PSA levels are low, or when the Gleason score is low.

Bladou continued and gave a short summary of the PSMA PET scan. The prostate-specific membrane antigen (PSMA) is located on the cell surface, and not released into circulation. It is reliably increased in PC, and is a very attractive imaging target. Its expression is increased with higher Gleason score. The PSMA used for imaging in PET scans is urea based and is a very small molecule with very rapid blood clearance. It targets the extracellular domain of the PSMA on the cell. Importantly, it has a very high target to background ratio. This radiotracer will emerge as the PC imaging gold standard and will be used in the future for:

  1. Therapy planning upon PSA recurrence
  2. Whole body staging of patients with high-risk disease
  3. Evaluation of therapy response
The outstanding session was then summarized with the nine dimensions of molecular imaging in PC:

  1. The x, y, and z dimensions which make up the volume of the lesion
  2. Location of the lesion (lymph node, vs. bone, vs. visceral)
  3. Intensity of lesions
  4. Change with time (dynamic)
  5. Polyclonality
  6. Androgen receptor-negative differentiation
  7. A predictive biomarker for PSMA
Imaging is important for PC diagnosis, and especially metastatic PC. It helps establish prognosis and determine the best therapy. Approximately 25% of metastatic castrate resistant patients progress on imaging without PSA rise, despite a median PSA around 80 ng/ml at baseline. Polyclonality has been shown in molecular studies and imaging can track polyclonality and AR-negative differentiation. Active tracking of AR-negative differentiation or resistance will enable initiation of new lines of therapy earlier or multimodal treatments.


References:
1. Hashim U Ahmed et al. Diagnostic accuracy of multiparametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 2017; 389:815-22.
2. V Kasivisvanathan et al. MRI-targeted or standard biopsy for prostate cancer diagnosis. NEJM 2018, May 10, volume 378, number 19
3. Alberto Marini et al. Development and internal validation of a site-specific, multiparametric magnetic resonance imaging-based nomogram for the prediction of extracapsular extension of prostate cancer. BJU Int. 2018 Apr 19. doi: 10.1111/bju.14353. [Epub ahead of print]
4. Gauvin S. et al. Initial single-centre Canadian experience with 18F-fluoromethylcholine positron emission tomography-computed tomography (18F-FCH PET/CT) for biochemical recurrence in prostate cancer patients initially treated with curative intent. Can Urol Assoc J. 2017 Jan-Feb;11(1-2):47-52. doi: 10.5489/cuaj.4068.

Presented by:
Frank Bladou, MD, Mcgill University, Montreal, Canada
Freddie Hamdy, MD, Oxford University, UK
Frederick Pouliot, MD, CHU de Québec et Université Laval, Quebec, Canada

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia
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