ASTRO 2022: Predictive Value of Ga68-PSMA PETCT-Based Response to Neoadjuvant Androgen Deprivation Therapy in Node Positive Prostate Cancer Treated with Radical Radiotherapy

(UroToday.com) The 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting held in San Antonio, TX between October 23rd and 26th, 2022 was host to a session that addressed studies aimed at improving outcomes for high-risk prostate cancer patients. Dr. Vedang Murthy presented the results of his group’s study evaluating the predictive value of 68Ga-PSMA PET/CT-based response to neoadjuvant ADT in node-positive prostate cancer patients treated with radical radiotherapy.

Dr. Murthy began his presentation noting that the diagnosis of positive node-only disease was relative common in countries with unscreened populations, such as India. In their practice, patients with N+M0 prostate cancer treated with radical intent undergo the following management plan:

Over time, Dr. Murthy and his partners anecdotally noted that patients with node-positive disease on PSMA PET/CT would usually have partial and/or complete responses to a few months of ADT.  

They however noted that response rates in the prostate gland were not as consistently favorable as those seen in the lymph nodes for the same patients.

Following these observations, the authors conducted a study to answer the following questions:

1. Do the prostate gland and pelvic lymph nodes respond differently to ADT?
2. Can the response in the prostate and nodes be quantified?
3. Could this response predict biochemical recurrence and disease control?

In essence, does the response observed on repeat PSMA PET/CT act as a prognostic biomarker of future oncologic outcomes? To this end, the authors included patients with newly diagnosed N=M0 prostate cancer (pelvic nodes only), diagnosed via ⁶⁸Ga PSMA PET/CT. These patients were planned for curative radiotherapy with ADT. Patients had paired ⁶⁸Ga PSMA PET/CT images available before and after neoadjuvant ADT. All patients had a minimum of one year follow-up post radiotherapy.

The authors evaluated the following PET imaging parameters in the initial and subsequent PET:

1. SUV max
2. PSMA tumor volume
3. Total lesion PSMA, defined as mean SUV x tumor volume

PSMA response was classified as follows:

1. Complete response
2. Partial response (decrease by ~30%)
3. Stable disease
4. Progression (increase by ~30%)

This study included 92 eligible patients with paired PSMA PET/CTs pre- and post-neoadjuvant ADT. The median duration of neoadjuvant ADT was 6 months and that of total ADT was 24 months. Patients did not receive systemic treatment intensification. For radiotherapy, the patients received dose-escalated, image-guided intensity-modulated radiation therapy in the form of moderate hypofractionation or SBR. The median EQD2 was 80 Gy (IQR: 78 – 84 Gy) A boost to gross nodes was given to 25% of the patients.

Consistent with previous anecdotal observations, the authors demonstrated that a complete response was seen in only 9% of the prostate glands, with a partial response in 62%. Conversely, in the pelvic nodes, a complete response was noted in 63%, with an additional 22% of patients having a partial response.

The differences in pre- and post-ADT PSMA PET parameters were quantified in the prostate gland and nodes, with consistent superior objective responses noted in the lymph nodes:

Next, the authors addressed whether PSMA PET findings correlated with oncologic outcomes. With a median follow-up of 43 months, biochemical failure was noted in 21/92 patients, with a 4-year biochemical failure-free survival of 75%. Patients with stable/progressive disease on PSMA PET/CT were significantly more likely to experience biochemical failure after radical XRT + ADT.

Furthermore, patients without biochemical failure had superior SUVmax prostate responses compared to those that experienced biochemical failure.

Furthermore, it appears that the results of the initial PSMA PET/CT are not sufficient to predict future risk of biochemical failure:

Based on these results, Dr. Murthy concluded as follows:

1. He emphasized that this is a hypothesis generating study. It appears that PSMA PET response to neoadjuvant ADT is prognostic of downstream oncologic outcomes.
2. Prostate and nodes respond differentially to ADT on PSMA-PET: CR in 9% of prostate and 63% of nodes
3. Patients with stable or progressive disease on repeat PSMA PET/CT were more likely to experience biochemical failure. It appears that SUV parameters on a single PSMA PET were not enough
4. Poor PSMA responders may be selected for early intensification

Presented by: Vedang Murthy, MBBS, Tata Memorial Centre, Mumbai, India

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2022 American Society of Radiation Oncology (ASTRO) Annual Hybrid Meeting, San Antonio, TX, Sat, Oct 22 – Wed, Oct 26, 2022.