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APCCC 2022: Are We Ready to Change Management Based on Next-Generation Imaging? NO

(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on high-risk and locally advanced prostate cancer and a presentation by Dr. Nicolas Mottet arguing that we are not ready for changes in management based on next-generation imaging. Dr. Mottet emphasized that what we are discussing is the everyday use of upfront PSMA PET/CT for staging, outside of a clinical trial, leading to guideline recommendations.


It is important to note that we are imaging these patients in order to characterize the extent of disease, as this will lead to an individualized treatment decision, with the premise that this will lead to improved outcomes related to these treatment decisions. Dr. Mottet notes that based on the proPSMA study,1 there is no question that PSMA PET/CT leads to more accurate detection of lesions. In this trial, 302 men were randomly assigned to conventional imaging (n=152) and PSMA PET-CT (n=150). PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0.0001). Additionally, this trial found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT.

However, Dr. Mottet notes that an extended pelvic lymph node dissection also provides improved risk stratification (pN0 vs pN1), although there has not been a study demonstrating improved overall survival based on a pelvic lymph node dissection for prostate cancer.

So, currently, with PSMA PET/CT imaging we have increased accuracy, risk stratification, and modification in management, but Dr. Mottet notes that we do not have delineation of an impact on outcomes. With regards to data on treatment change, studies thus far have noted an 18%-21% rate of change in treatment based on PSMA PET/CT results. There is no outcome data available, therefore Dr. Mottet notes that these treatment changes are purely based on assumptions at this point in time. Dr. Mottet also highlighted that the risk of using PSMA PET/CT for staging as standard of care is that if it is outside of a clinical trial/prospective cohort, we will never know the added value of PSMA PET/CT in this context. Even if the PSMA PET/CT is negative, an extended pelvic lymph node dissection is still needed given the reported sensitivities for PSMA PET/CT of 33%-85%: 

Nicolas Mottet-1.jpg

With regards to treating the M1 disease sites, there is very little prospective data available, with 4 studies combining data on 158 patients (109 in the experimental arms), including a mix of N1 and M1 disease with various EBRT regimens. Dr. Mottet emphasizes that without data, there will be those that are over-treated (leading to increased toxicity) and those that are undertreated (leading to worse survival). In the past several years there have been several editorials written cautioning against widespread PSMA PET/CT use. Hussain and colleagues wrote in 20202 that “without prospective validation, the concern is that it may lead either to under-treatment by not offering locoregional or adjuvant therapy in otherwise potentially curative or life-prolonging settings or to overtreatment with associated increased morbidity.” Secondly, in 2022, Hussain and colleagues noted that for patients with negative conventional imaging but PSMA PET/CT positive we should be prioritizing these patients for clinical trials.3

Dr. Mottet concluded his presentation discussing that we are not yet ready for changes in management based on next-generation imaging with the following take home messages:

  • PSMA PET/CT for staging is of major interest
  • Outcome data based on treatment change is non-existent
  • We should only be using PSMA PET/CT for staging in clinical trials/prospective cohorts, which is the only way to prove that outcome is improved

Presented by: Nicolas Mottet, MD, PhD, University Hospital St. Etienne, St. Etienne, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Annual Hybrid Meeting, Lugano, Switzerland, Thurs, Apr 28 – Sat, Apr 30, 2022.

References:

  1. Hofman MS, Lawrentschuk N, Francis, RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomized, multicentre study. Lancet 2020 Apr 11;395(10231):1208-1216.
  2. Hussain M, Lin D, Saad F, et al. Newly Diagnosed High-Risk Prostate Cancer in an Era of Rapidly Evolving New Imaging: How do we Treat? J Clin Oncol. 2021 Jan 1;39(1):13-16
  3. Hussain M, Carducci MA, Clarke N, et al. J Clin Oncol [in press]. 
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APCCC 2022: Are We Ready to Change Management Based on Next-Generation Imaging? YES