(UroToday.com) Advances in imaging have dramatically reshaped prostate cancer diagnosis, staging, and treatment. While multiparametric MRI (mpMRI) of the prostate has dramatically changed prostate cancer diagnosis, molecularly-targeted imaging has reshaped disease staging and detection of recurrent disease. Conventional imaging approaches using including computed tomography (CT) and bone scan have relatively limited sensitivity to detect disease recurrence following initial local therapy. A number of studies have demonstrated that prostate-specific membrane antigen (PSMA) targeting PET radiopharmaceuticals detect disease not identified based on conventional imaging, with greater accuracy, for initial staging and detection of biochemical recurrence. However, its role in response assessment has not been thoroughly investigated.
In the Center for Therapy Excellence Young Investigator Award session at the Society of Nuclear Medicine & Molecular Imaging (SNMMI) 2021 Annual Meeting, Dr. Qaid Ahmed Shagera presented an assessment of the role of 68Ga-PSMA PET/CT to assess response for patients with metastatic prostate cancer undergoing taxane-based chemotherapy and its relationship with patient outcomes.
To do so, they retrospectively enrolled patients with metastatic hormone-sensitive and castration-resistant prostate cancer (mHSPC and mCRPC) who underwent a 68Ga-PSMA PET/CT scan within one month before and up to 3 months after docetaxel or cabazitaxel treatment. Patients had no therapy modification between the scans.
The authors assessed biochemical response, defined as a decrease of the prostate-specific antigen (PSA) level by ≥50% from the baseline. Prostate-specific membrane antigen (PSMA) expression changes on PET/CT were measured using whole-body PSMA tumor volume (PSMA-TV), using the fixed SUV=3 method. The response was assessed on a per-patient basis. The authors' classified patients as PSMA-PET non-responders (PET-NR), including patients with ≥2 new lesions or increase of PSMA-TV by ≥30% (progressive disease, PD) or PSMA-TV change between ±29% (stable disease, SD) and PSMA-PET responders (PET-R), including patients with the disappearance of all PET-positive lesions (complete response, CR), or a decrease of PSMA-TV by ≥30% (partial response, PR).
The correlation between the PSMA-PET response and biochemical response was evaluated. Cox regression analyses and Kaplan-Meier curves were used to assess the relationship between PSMA-PET response criteria and patient outcomes (PFS and OS) as defined by PCWG3 criteria.
The authors examined 37 patients, of whom 8 had mHSPC and 29 had mCRPC. Twenty-one patients received docetaxel and 16 received cabazitaxel, with a median of 6 cycles administered. 18 patients had a biochemical response, while the remaining 19 did not.
On the basis of PSMA-PET/CT consensus criteria, 19 patients were classified as PSMA-PET responders (of whom, 6 had a complete response and 13 had a partial response) and 18 were PSMA-PET non-responders (of whom, 17 had progressive disease and 2 had stable disease). PSA-based response and PSMA PET/CT-based response were concordant in 95% of patients, with 18 patients having neither a response by biochemical or PSMA-PET/CT criteria and 17 having both biochemical and PSMA-PET/CT based response (Phi = 0.89, p<0.0001).
There were discordant results for two patients. The first had evidence of PSMA-PET/CT response (PSMA-TV decreased by 42%) but not biochemical response (PSA increased by 96%). The second had evidence of biochemical response (PSA decreased by 52%) but progressive disease by PSMA-PET/CT (>2 new lesions).
The authors further demonstrated significant associations between the number of cycles received (≥6 vs <6), disease state (mHSPC vs mCRPC), baseline hemoglobin, and baseline alkaline phosphate with PSMA-PET response.
Over a median follow-up of 20 months, 16 patients had died. Patients who were classified as non-responders by PSMA-PET/CT criteria had worse overall survival: 12-month OS of 58% vs 100% and 24-month OS of 42% vs 94% (HR 4.64, 95% CI 1.86—11.58, p=0.001).
These associations remained significant after adjustments for disease stage (mHSPC vs. mCRPC), PSA level, hemoglobin and alkaline phosphatase.
Patients who were non-responders by PSMA-PET/CT criteria had statistically significant shorter progression-free survival (median PFS: 5.4 months vs. 10 months).
The authors, therefore, conclude that this retrospective analysis suggests that PSMA PET/CT is a promising imaging tool to evaluate the response to taxane-based chemotherapy in patients with metastatic prostate cancer as responses based on PSMA-PET/CT are independently associated with patient outcomes including progression-free and overall survival. Ongoing work is assessing this in a prospective fashion.
Presented by: Qaid Ahmed Shagera, MD, Institut Jules Bordet, Université libre de Bruxelles
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Contact: @WallisCJD on Twitter at the Society of Nuclear Medicine & Molecular Imaging - 2021 Virtual Meeting, June 11-15, 2021