PCWG3 and Oncology Endpoints Webinar Summary PCWG3 and PSMA PET/CT Response Criteria

Prostate cancer is one of the most common cancer types in men. With bone as a frequent metastatic site, response assessments for prostate cancer have additional considerations beyond RECIST 1.1. In our recent webinar, MERIT outlined the fundamentals of the Prostate Cancer Working Group 3 (PCWG3) response criteria, data collection, and response assessment as well as imaging using bone and PSMA PET/CT scans in prostate cancer.

The second part of our summary focuses on PCWG3 response criteria, PSMA PET/CT response criteria, data collection, and response assessment. Gene Kim is MERIT’s Clinical Scientist and presented the response criteria portion of the webinar. He received his Doctor of Pharmacy (Pharm.D.) from the University of Wisconsin-Madison and has a bachelor’s degree in Neurobiology.

Click here to see the full webinar

PCWG3 Response Criteria

Introduction

The PCWG3 criteria was developed by the Prostate Cancer Working Group beginning with PCWG2 in 2008 and followed up by PCWG3 in 2016. The indication for this imaging assessment methodology is Metastatic Castration-Resistant Prostate Cancer (mCRPC) with the primary tumor site being the prostate with possible bone metastasis and visceral soft tissue metastasis.

PCWG3 suggests the use of the following response criteria for bone scan assessment as a radiographic outcome:

Due to bone lesions being a very common site of metastasis in prostate cancer, as well as issues with bone lesion flares from antineoplastic therapy, PCWG3 suggest rules for reading a bone scan using nuclear medicine. Therefore, there are two components for PCWG3 assessment: RECIST 1.1 for the rest of the body and PCWG3 for bone lesions. The overall response can be reported in two compartments, or a combined response may be derived as defined per study protocol.

Lesion Categories: Extra-Skeletal and Skeletal

Extra-skeletal lesions are defined as any non-bone lesions such as soft tissue or visceral metastasis in such locations as lung, liver, lymph nodes, etc. Extra-skeletal lesions are assessed by RECIST 1.1 lesion categories of Target Lesions, Non-Target Lesions, and New Lesions using the standard RECIST 1.1 criteria.

The lesion categories for the PCWG3 specific criteria are for skeletal or bone lesions and will collect the following information:

• Bone Lesion ID
• Lesion State: Presence/Absence
• Baseline Bone Lesion Count
• Anatomical Location (skull, thorax, spine, pelvis, extremities)

Note there is no measurement of the lesions and no limit on the number of lesions categorized, unlike the RECIST 1.1 Target Lesion criteria. Record only lesions that are related to a prostate cancer metastasis and exclude lesions that are not truly malignant such as fractures or inflammatory processes that may be visualized in the bone scan.

At follow up, new bone lesions are recorded as follows:

• Bone Lesion ID
• Lesion State: Presence/Absence
• Bone Lesion Count
• Anatomical Location (skull, thorax, spine, pelvis, extremities)
• Total new lesion number compared to Baseline and Week 8 assessment
• Total new lesion number compared to Week 8 (for post-week 8)

As with the baseline, there is no measurement of the lesions and no limit on the number of lesions categorized.

Imaging Modalities/Timepoints

The recommended imaging modalities are bone scan and CT/MRI. The imaging timepoint recommended for prostate cancer is usually about 8 to 9 weeks after baseline.

Example

• Baseline
• 1st imaging at Week 8 or 9 (or predefined first timepoint)
• 2nd imaging at Week 16 or 17

Response Criteria

Response criteria outcome for the extra-skeletal lesions such as soft tissue or visceral metastasis will be reported per RECIST 1.1 definitions of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD).

The bone lesion response outcomes have only two delineations and will be reported as either Progressive Disease (PD) or Non-Progressive Disease (Non-PD). Progression is defined by using what’s referred to as the 2 + 2 rule. Note that the Week 8 scan is the post-baseline reference image.

The 2 + 2 rule is defined as follows:

PSMA PET/CT Response Criteria

PSMA PET/CT PPP

For PSMA PET/CT imaging in prostate cancer, there are several response assessment criteria that have been proposed recently in various publications. One of these is the PSMA PET Progression (PPP) Criteria. The PPP is meant to be used for locoregional or systemic therapy to determine Progression vs. Non-Progression based upon a PSMA PET/CT scan. The new lesion assessment is based on location, size, and intensity. This is different from the bone scan criteria which has had issues with not being able to quantify exactly how pre-existing or new lesions have been responding or progressing based on the bone scan.

PD is defined as one or more of following:

• Two or more new PSMA-positive distant lesions
• One new PSMA-positive lesion + clinical data indicative of PD
• Size increase or uptake increase by 30% or more + clinical data indicative of PD

PPP Limitations:

• Due to its recent publication, it is not yet validated
• 30% cut-off is arbitrarily chosen without supporting evidence

PSMA PET/CT RECIP 1.0

Another novel response assessment evaluation developed for PSMA PET/CT imaging is the RECIP 1.0 criteria. This was based on a retrospective, multi-center study of mCRPC patients treated with Lu-PSMA therapy. The study showed a correlation with Overall Survival (OS) outcome where OS was superior in PR/SD versus PD with statistically significant differences between these response groups.

RECIP 1.0 uses tumor volume based upon PSMA PET/CT imaging. It includes delineation of response into CR, PR, SD, and PD as follows:

RECIP 1.0 Limitations:

• Has not yet been prospectively validated
• Subject pool had no bone scan availability and cannot compare prognostic value of RECIP 1.0 to PCWG3
• No correlation to PFS available due to inconsistent clinical data availability

Highlights from the Q and A

Q We are currently using PCWG2 for some of our existing studies. What are the main benefits and differences in implementing the updated PCWG3 criteria?
A There are not a great many updates from PCWG2 to PCWG3. There are new recommendations to move from RECIST 1.0 to RECIST 1.1 particularly for visceral metastasis, but other than that, the bone scan reading assessment and the 2 + 2 rule for progression assessment has been maintained from PCWG2 to PCWG3.

Q Is all the imaging information as discussed today captured in a study’s protocol?
A Imaging is written into a study’s protocol as part of the schedule of assessments so that sites are aware of the appropriate imaging that must be performed at each timepoint. The basic information in the protocol, however, is greatly expanded in the Imaging Charter. The Imaging Charter becomes the guiding document for all study imaging that outlines workflows, processes, and reading criteria. The reading criteria might even be slightly modified for a given study, which would be captured in the Charter.

Q Can you evaluate images for a given patient collectively over time to get an overview of the disease progression of the patient while participating in a trial?
A Yes, this is made possible by a sequential locked timepoint presentation. Depending on the reading paradigm, a reader or two readers will assess a patient over time. Readers will assess a patient timepoint by timepoint the same way a site would. The reader is presented with the timepoints one by one in order, and they’re locked, like what happens at a site. The sequential locked timepoint presentation can help reduce bias in the reading process.

Click here to see the full webinar