What’s new in PCa high-risk local treatment, and how useful is MRI?
Day three began with a game changing session, followed by scientific updates and lively debate in Plenary 5 on PCa high-risk local treatment. Experts Dr. Alberto Bossi (FR) and Prof. Alberto Briganti (IT), chaired this highly informative morning.
Game Changing Session
During the game changing session, Prof. Declan Murphy delivered encouraging initial results on the clinical trial protocol for LuTectomy: A single-arm study of the dosimetry, safety and potential benefit of 177 Lu-PSMA-617 prior to prostatectomy.
According to Prof. Murphy, the biochemical response after LuPSMA-617 saw an 80% reduction in PSA levels, and the BCR (biochemical recurrence) free survival was 80% at a median follow-up of 12 months.
“LuPSMA prior to surgery is safe and the surgery is straightforward. There were no serious adverse events, and non-target areas such as salivary glands and kidneys received minimal radiation. Cohort B patients receive two cycles and we will report that data soon.”
Prof. Steven Joniau (BE) delivered results on ARNEO: A randomised phase II trial of neoadjuvant degarelix with or without apalutamide prior to radical prostatectomy for unfavourable intermediate- and high-risk prostate cancer.
He concluded from this research that patients treated with degarelix + apalutamide achieved a significantly better tumour response compared to patients treated with degarelix plus a matched placebo. PSMA PET estimated volumes and PSMA PET SUVmax after neoadjuvant therapy predict pathological response and PTEN (phosphatase and tensin homologue) loss is a negative predictor of MRD (minimal residual disease). There is a solid basis for future Phase 3 trials.
How does MRI change the local strategy in high-risk men?
In Dr. Giorgio Gandaglia’s (IT) state-of-the-art lecture “How does MRI change the local strategy in high-risk men? – Surgery”, he stated that MRI in high-risk patients is important to provide the prognostic information to guide the delivery of tailored surgical approaches; to identify nerve-sparing candidates; and to identify patients who should receive wider excision.
According to Dr. Gandaglia, MRI does have an impact on changing surgical plans in the rising risk category by up to 52%, and the surgical decision-made based on MRI was correct on average in 91% of the high-risk group.
He cited research by Baack Kukreja et al. PCAN 2020 that after mpMRI review there was a 13% increase in the overall approximately planned surgery (from 72% to 85%). After mpMRI review, the bladder neck sparing was changed to the appropriate surgical plan in 37% of cases, and 98% of patients had a change in the degree of planned nerve sparing: wider excision in 32% and increased nerve sparing in 24%.
According to Dr. Gandaglia, clinicians should be aware that up to 40% of high-risk patients with a negative MRI have microscopic extracapsular extension (ECE) or seminal vesicle invasion (SVI).
“In a meta-analysis of 75 studies, MRI appeared to have high specificity but poor sensitivity for detection of ECE, SVI, and overall stage T3. mpMRI cannot detect microscopic ECE and its sensitivity increases with the diameter of the lesion. The low sensitivity limits the role of MRI in preoperative surgical planning.”
Dr. Gandaglia summarised his recommendations for MRI in preoperative staging in high-risk PCa:
- If bilateral ECE or SVI at MRI, then wide excision (high specificity)
- If unilateral OC or ECE disease at mpMRI, consider unilateral nerve sparing in men with index lesion <15mm without GG (grade group) > lesions
- If not ECE or SVI at MRI, then use multivariable risk calculators to tailor the surgical approach
Novel risk groups should include MRI, as this prognostic information is needed, and mpMRI together with clinical characteristics should guide towards a more conservative vs. extensive resection to deliver a tailored surgical approach.
In his state-of-the-art lecture, “How does MRI change the local strategy in high-risk men? – Radiation therapy”, Prof. Gert De Meerleer (BE) stated that MRI is vital to treat high-risk patients in 2022, specifically to combat biochemical recurrence (BRC).
“Boosting the dominant intraprostatic lesion with modern radiation improves cure. And it is cure that matters to patients, much more than the overall survival (OS) dogma,” concluded De Meerleer.