Targeted focal therapy should be held to oncologic standards – and so there are some steps that needed to be developed and met before it becomes an accepted standard: develop a 3D model, method to identify significant lesions, clinical studies to identify in vivo, obtain satisfactory ablation, and have long-term outcome data. We, as a field, are working towards that goal now.
In the interest of brevity, I am going to highlight the key points from each of the speakers. Most of these speakers are experts in the field – and often have research work that contradicts their debate position (which is often used by their opponents).
Dr. Pinto started the debate arguing that mpMRI is capable of identifying significant lesions. He started with his disclosures – including the fact that he fully accepts that mpMRI may not detect 100% of tumors (but what diagnostic test does?). He still feels that mpMRI of the prostate is still the most significant advance our field has seen in the past 4 decades in terms of imaging.
Even the index patient listed, mpMRI was critical to his cancer diagnosis and eventual treatment. Indeed, as tumor size increases, the performance of mpMRI increases. His team at the NIH has had a long history looking at mpMRI performance by comparing mpMRI results to radical prostatectomy whole mount specimens (rad-path correlation).
He then highlighted the two more recent studies (PROMIS and PRECISION) that demonstrated in large, randomized clinical trials the added diagnostic benefit of fusion biopsy over standard systematic biopsy – and in particularly, for clinically significant prostate cancer1, 2 .This was also consistent with NIH data3
On the other hand, how many cancers are being missed by mpMRI fusion biopsy? In a prospective study at the NIH, Dr. Pinto and colleagues4 found that mpMRI missed approximately 26/162 (16%) of cancers. But of those that it missed, 18 were Gleason 7 disease and only 8 were (5%) were Gleason 8-10.
So mpMRI appears to be a good tool to identify csPCa and used as a modality to guide targeted therapy.
Dr. Eggener argued that mpMRI is NOT capable of identifying lesions for targeted focal therapy. Most of his disclosures would be an issue – if he was arguing FOR targeted focal therapy. His main disclosure is that he is a proponent of mpMRI and uses it often.
He concedes Dr. Pinto’s point that a biopsy with mpMRI fusion supercedes a biopsy without mpMRI guidance (standard systematic biopsy). Based on the strength of randomized controlled trials and strong well designed non-randomized trials.
But, saying that mpMRI is capable of identifying ALL lesions for focal therapy is like putting the cart before the horse – we are not there yet! The three areas it is still lacking are: identifying all cancers of potential significant, predicting extracapsular extension and estimating tumor volume.
- MRI misses a meaningful proportion of csPCa
- In 588 consecutive men undergoing RP with a prior negative mpMRI, ~60% had meaningful disease that were missed. Of tumors > 2 cm, 22% were missed. Of tumors that were GG3- 5, 25% were missed. Therefore, of solitary “clinically significant” PCa, 17% were missed
- In a recent meta-analysis the NPV ranges between 80-95%6
- MRI is very poor at predicting ECE
- Sensitivity and specificity were 58% and 68%8
- Indeed, in a study by Pinto and colleagues accuracy remained poor (66%)6
- In a RCT having a pre-operative MRI had no impact on surgical margin rates7
- MRI typically underestimates tumor volume
- MRI underestimates tumor volume by ~2 mm, or more in larger lesions with PIRADS score 4 or GG2-5. A simulated tumor treatment margin of 9 mm (~1 cm) needed to ensure complete histological tumor destruction
- In a study by Sun et al, underestimation was as below10
- Based on this, he argues that MRI is a valuable imaging tool for screening and targeting. But, it has significant limitations.
Dr. Taneja built on Dr. Pinto’s arguments. He also argued that MRI targeted focal therapy is ready for prime time.
My main take-home from his talk is as follows: we know that PCa is a multifocal disease. MRI does not detect all cancer. But, as we move into the focal therapy era, we need to accept that it will NOT treat all cancer foci – cancer left behind will usually be low-grade, indolent, small volume disease.
What he therefore asserts:
- The disease identified by mpMRI is biologically different than PCa missed by mpMRI – more aggressive and more biologically relevant
- Focal therapy implies a new paradigm for prostate cancer – so we must think about it differently
- The desire to identify and treat every prostate cancer is fossilized – and got us into trouble before
- If focal therapy is to be done, mpMRI is an excellent tool to guide us
- Therapeutic goal is distinct from conventional therapy – goal is prevention of metastases/mortality. “The patient may not be cancer-free – but they will hopefully be free of cancer death.”
Dr. Mendoza-Velez finished off the debate by reiterating many of Dr. Eggener’s points. Additional points he made are below:
- Hardware limitations – hardware limitations (lots of components that can affect quality of the study and therefore the diagnostic ability – and more importantly therapeutic efficacy)
- Interreader variability – this still remains a big issue for the general use of mpMRI. Even for diagnosis, mpMRI reporting can be highly variables based on institution, reader experience, etc. This is work that has been regularly reported by Dr. Pinto and colleagues.
- Target localization remains a significant concern
- Assessing patients for hemiablation11, they found that: 48% of patients eligible by fusion biopsy were ineligible on prostatectomy whole-mount pathology, 41 patients (~45%) had discordant tumors on contralateral side of the index lesion (21 crossed midline, 20 with undetected contralateral tumors); 10 of those 41 patients had csPCa
Moderator: E. David Crawford, MD, University of Colorado
Samir Taneja, MD, NYU Langone Medical Center
Peter Pinto, MD, National Cancer Institute, National Institutes of Health
Scott Eggener, MD, University of Chicago
Arturo Mendoza-Velez, MD, Hospital Medica Sur
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University @tchandra_uromd, @JEFFUrology at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois
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