(UroToday.com) The 2022 Advanced Prostate Cancer Consensus Conference (APCCC) Hybrid Meeting included a session on the management of non-metastatic castrate-resistant prostate cancer (nmCRPC), and a presentation by Dr. Alberto Briganti discussing the disadvantages of using novel imaging in this disease space. Dr. Briganti notes that the EAU guidelines for high risk nmCRPC are a PSA doubling time of <= 10 months during continuous ADT, which is consistent with the three key trials in the nmCRPC disease space: SPARTAN1 (apalutamide), PROSPER2 (enzalutamide), and ARAMIS3 (darolutamide):
The revolution of imaging includes PSMA PET/CT, which can detect metastatic disease in almost all (~98%) of patients classified as being nmCRPC by conventional imaging:4
Based on these findings, Dr. Briganti asks: What is the benefit of using novel imaging in a man with CRPC if this patient has already a proven benefit by ARTA in the case of negative (if high risk) conventional imaging? Maybe this is different in non-high risk nmCRPC? Improved identification of metastatic disease does not justify abandoning standard of care treatment options in conventionally imaged patients with nmCRPC.
Dr. Briganti then presented a clinical case of a 72 year old male without significant comorbidity except obesity (BMI 32 kg/m2), who was diagnosed with incidental prostate cancer diagnosed in 2019 (Gleason 8+8, pT1b) and started on ADT without treatment of the primary. His PSA at the time of ADT was 0.44 ng/mL (cN0M0). One year after ADT initiation his PSA was 1.13 ng/mL, after another 3 months was 1.49 ng/mL, and after another 3 months was 2.1 ng/mL for a PSA doubling time of 6 months. He subsequently had conventional imaging, which was negative, and then a choline PET/CT which showed uptake at the level of the left seminal vesicle and one common iliac lymph node. The patient was proposed to undergo a salvage radical prostatectomy with extended pelvic lymph node dissection.
Based on the EAU guidelines, there is weak evidence to suggest that men should be offered a PSMA PET/CT scan for those with a persistent PSA > 0.2 ng/mL if the results will influence subsequent treatment decisions. Dr. Briganti emphasized that a PSMA PET/CT should not be performed for routine follow-up if management of the patient is unlikely to change, and in patients with CRPC, this would lead to imaging-based changes in treatment decisions. It remains unclear if the use of PSMA PET/CT in this setting improves outcomes.
Is the use of novel imaging in nmCRPC really beneficial? For high risk nmCRPC, they should receive apalutamide, enzalutamide, or darolutamide. For those that are CRPC and subsequently have a PSMA PET/CT that finds lesions:
- Should patients with nmCRPC with metastasis detected on PET/CT be considered mCRPC?
- Should we perform metastasis directed therapy in case of positive imaging for patients with oligometastatic M+ disease?
- Should we treat the primary in case of local positive imaging?
Dr. Briganti suggests that PSA kinetics are key for such decisions on metastasis directed therapy.
Highlighting data from a recent consensus statement that is under review, Dr. Briganti notes that this panel included 21 prostate cancer experts from various disciplines in order to derive expert opinions regarding the use of PSMA-based imaging and therapy to develop interim guidance. Based on several rounds of discussion, there was uncertainty regarding the use of PSMA PET/CT in patients with nmCRPC. The reasons for this uncertainty included (i) patient heterogeneity, (ii) lack of long-term data regarding the benefit of metastasis-directed therapy in CRPC (as a result of detecting lesions using PSMA PET/CT), (iii) lack of data on treatment response and how to follow these patients, (iv) lack of data regarding the appropriate sequencing of treatment, and (v) lack of data about cost-effectiveness.
Dr. Briganti notes that the studies assessing prospective/retrospective data testing metastasis-directed therapy in oligo-progressive mCRPC are small, lacking PSA doubling time data, and are wrought with heterogeneity. A summary of the characteristics of these studies is as follows:
With regards to consensus statements on PSMA PET/CT response assessment criteria, there was a consensus that 3 months is the minimal timing for performing PSMA PET/CT after initiation of hormonal intervention. Additionally, there was consensus regarding several definitions:
- Complete response: complete disappearance of any lesion with tracer uptake
- Partial response: reduction of uptake and tumor volume by >30%
- Stable disease: change of uptake and tumor volume +/- <= 30% and no new lesions
- Progressive disease: appearance of two or more new lesions and/or increase of uptake of tumor PET volume > 30%
Additionally, there was consensus regarding not performing PSMA PET/CT in the majority of mCRPC to assess disease progression.
There are several questions that arise regarding treatment sequence after the use of PSMA PET/CT, for which the answers are currently unknown:
- Should metastasis directed therapy be added or precede ARTA in men with mCRPC at PET/CT?
- If PET/CT is done in nmCRPC how should we follow these patients and when should we add conventional imaging?
- Is it beneficial for patients to perform reiterated metastasis directed therapy? There is low toxicity, but what about efficacy?
Dr. Briganti concluded his presentation of disadvantages of using novel imaging in nmCRPC with the following take-home messages:
- Novel imaging approaches represent sensitive options to detect metastatic sites in men with CRPC
- The proven benefit of using novel imaging approaches is unclear given the lack of evidence based on all mentioned limitations regarding patient selection, imaging interpretation and standardization, prospective data of metastasis directed therapy and follow-up assessment
- The need for standardized reporting is crucial
Presented By: Alberto Briganti, MD, PhD, San Raffaele, Milan, Italy
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:
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.
- Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474.
- Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
- Fendler WP, Weber M, Iravani A, et al. Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2019 Dec 15;25(24):7448-7454.