ASCO GU 2020: Challenging Cases in Prostate Cancer – Case 1: PSMA PET/CT Imaging

San Francisco, California (UroToday.com)  The first case presented was that of a 54-year-old otherwise healthy man who underwent radical prostatectomy after biopsy-confirmed prostate cancer. Pathology revealed a pT3b tumor, Gleason 4+3 = 7 with tertiary Gleason 5, pNx, negative surgical margins. The patient was lost to follow-up but then eventually returned and was found to have a PSA of 1.6 ng/mL, confirmed two weeks later at 1.8 ng/mL.

The first question raised was surrounding the next imaging step. Specifically, does the audience agree with the recommendation to pursue PSMA PET/CT imaging? A discussion of the benefits of PSMA-PET in this context ensued.

PSMA-PET has been shown to identify sites of disease in the context of biochemical recurrence at prostate-specific antigen (PSA) thresholds lower than conventional imaging, and the rate of PET positivity rises with PSA level.

correlation of psa level after radical prostatectomy and psma pet positive lesions

Positive findings on PSMA-PET have been shown in a recent meta-analysis to impact clinical management decisions.1 Specifically, as shown below, the initial therapeutic strategy was altered away from focal therapy towards more systemic therapy.

clinical impact of enhanced tumor detection by psma pet

Returning to the case, a PSMA PET/CT was performed. It is important to note that this modality is currently not widely available in the USA, but this will likely change in the near future. The scan revealed four PSMA-avid perirectal and iliacal lesions. The next question raised was for next treatment steps: surveillance vs salvage lymph node dissection, salvage radiation, or androgen deprivation therapy (ADT) monotherapy.

Most audience members voted for salvage radiation. A discussion of each of the presented options ensued.

Regarding salvage lymph node dissection, there is no randomized control trial data to support this, though one has been recently opened in Sweden.

study on salvage lymph node dissection

There is one study that retrospectively examined salvage lymphadenectomy across multiple centers using PET-directed patient selection. This is summarized here:

largest experience with salvage lymphadenectomy

Ultimately, it is not clear that salvage lymphadenectomy, even based on PET/CT imaging, is an effective intervention. Dr. Eggener said that the only patients he might consider salvage lymphadenectomy in are those that might be low risk for further metastatic disease (favorable Gleason score, etc) in whom the surgery is technically feasible.

A discussion of the role of radiation in the setting of nodally recurrent prostate cancer then was held. The evidence for this comes in part from the STOMP trial showing tolerability, improvement in biochemical recurrence-free and ADT-free survival.2 What is the best way to deliver radiation? Elective radiation to nodal basins (ENRT) versus SBRT was discussed with the following summary:

elective nodal vs sbrt for nodal recurrent prostate cancer

Ultimately Karen Hoffman, a radiation oncologist, discussed how she would recommend ENRT as well as prostatic fossa radiation with a higher dose delivered to areas of gross disease. She would also recommend one to two years of ADT, extrapolating from the known benefit of adding ADT to radiation in high-risk localized patients. Given the patient’s relatively low PSA level, the discussant described that it would be important to ensure the PSA was appropriately trending downwards while on ADT. Though the patient is quite young, the risk of secondary malignancy does not outweigh the need for disease control in this case.

Finally, a discussion of PSMA-PET was held in more detail. As alluded to above, PSMA-PET is effective and changes therapeutic decision making (without evidence supporting the long-term efficacy of these therapeutic changes). Importantly, compared to other PET/CT modalities such as fluciclovine, PSMA-PET appears to have higher detection rates and better inter-reader concordance rates.

detection rates

Presented by:

Charles J. Ryan, MD—Chair: B.J. Kennedy Chair in Clinical Medical Oncology at the University of Minnesota and Director of the Division of Hematology, Oncology and Transplantation.
Markus Graefen, MD—Chair: Professor of Urology & Chairman of Martini-Klinik, Prostate Cancer Center at the University Medical Center Hamburg-Eppendorf.

Scott Eggener, MD
, Professor of Surgery and Radiology, Vice-Chair of Urology, Bruce and Beth White Family Professor of Urologic Oncology, Director, University of Chicago High Risk & Advanced Prostate Cancer Clinic (UCHAP), Chicago University, Chicago, Illinois
The Urologist Perspective

Karen Elizabeth Hoffman, M.D., M.H.Sc., M.P.H. 

Department of Radiation Oncology, Division of Radiation Oncology, Associate Professor, Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Radiation Oncologist

Celestia S. Higano, MD, FACP
Professor, Department of Medicine, Division of Oncology, Professor, Department of Urology, The University of Washington
Medical Oncologist

Thomas Hope, MD
Associate Professor, Radiology, School of Medicine, University of California, San Francisco
Radiologist



Written by: Alok Tewari, MD, PhD, Medical Oncology Fellow, Dana-Farber Cancer Institute, Boston, Massachusetts at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California 

References:

1. Han, Sangwon, Sungmin Woo, Yeon Joo Kim, and Chong Hyun Suh. "Impact of 68Ga-PSMA PET on the management of patients with prostate cancer: a systematic review and meta-analysis." European urology 74, no. 2 (2018): 179-190.

2. Ost, Piet, Dries Reynders, Karel Decaestecker, Valérie Fonteyne, Nicolaas Lumen, Aurelie DeBruycker, Bieke Lambert et al. "Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial." (2017).

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