Dr Calais on Controversies in the Treatment of Patients With Prostate Cancer

Jeremie Calais, MD, PhD, physician, nuclear medicine, associate professor, Department of Molecular and Medical Pharmacology, director, Theranostics Program, Ahmanson Translational Theranostics Division, faculty member, the Jonsson Comprehensive Cancer Center, faculty member, the Institute of Urologic Oncology, faculty member, the Physics and Biology in Medicine Graduate Program, University of California, Los Angeles (UCLA), UCLA Health, discusses controversies and unresolved questions in the treatment of patients with prostate cancer.

2024 US Prostate Cancer Conference (USPCC),

 medical oncologists, urologists, and many other individuals came together to provide clinicians with valuable knowledge and confidence to maintain state-of-the-art care and optimize outcomes for patients with prostate cancer. Calais begins by stating that one such area of interest at the meeting was controversies within the field; numerous controversies and unresolved queries persist across various subjects. Calais says that from his perspective, as a nuclear medicine specialist, he finds it highly beneficial to participate in this gathering of predominantly medical oncologists.

Although urologists, radiation oncologists, and nuclear medicine specialists are also present at the meeting, most of the attendees are medical oncologists, he states. Nevertheless, it's invaluable to foster this multidisciplinary environment for addressing inquiries, Calais adds.

Prostate cancer is increasingly intricate, with a surge in diagnostics, biomarkers, and treatment options, necessitating a multidisciplinary treatment approach, Calais continues. Consequently, numerous uncertainties emerge, and as more tests are conducted and more advancements are made, more questions arise, he elucidates. Specifically, within nuclear medicine, there's ongoing exploration of optimizing PET imaging for generating superior treatment outcomes and enhancing the utilization of prostate-specific membrane antigen–targeted radiopharmaceutical therapy, Calais notes.

These areas represent significant points of discussion and potential contention for nuclear medicine practitioners at this meeting, he explains. Moreover, the complexity of these discussions often leads to further exploration and the identification of specific expertise questions, expanding the scope of inquiry and fostering collaborative efforts among specialists, Calais concludes.

Videos

Jeremie Calais, MD, PhD, discusses controversies and unresolved questions in the treatment of patients with prostate cancer.

Jeremie Calais, MD, MSc, associate professor of nuclear medicine and theranostics, David Geffen School of Medicine, University of California, Los Angeles (UCLA), UCLA Health, discusses the role of prostate-specific membrane antigen (PSMA)-PET imaging in metastatic-castrate resistant prostate cancer (mCRPC), and touches on the importance of integrating PSMA-PET imaging into community settings for clinical practice.

The development of PSMA-PET scans has allowed for earlier and more accurate detection of distant metastases in the lymph nodes, leading to a wider selection of treatment approaches, including radioligand therapy or chemotherapy, Calais begins. 

PSMA-PET scans have a special resolution that improves its detection capabilities, giving the scans an advantage over previous imaging techniques, Calais continues. Although the improved sensitivity of PSMA-PET imaging is beneficial, the expectations for the predictive value of this technique can be high, Calais qualifies. Clinicians may be tempted to de-escalate therapy in patients who produce a negative PSMA-PET scan, but this is not always the correct approach, he says.

Because the sensitivity of PSMA-PET imaging is around 40%, some patients with microscopic metastatic disease may still remain unidentified, Calais says. Furthermore, there is a whole-stage migration effect with more sensitive imaging techniques, he adds. This could potentially change the definition of mCRPC and requires a re-evaluation of how to apply prior data in this space, Calais states. 

As a novel, emerging technology, PSMA-PET imaging has been primarily performed in academic centers, Calais notes. Although it has begun to be utilized more widely in community settings, there is a large learning curve associated with this approach, Calais explains. Therefore, it is important for prescribing physicians, radiologists, medical oncologists, and nuclear medical physicians to work collaboratively to determine the best application of PSMA-PET scans, he states. This multidisciplinary approach is especially important because PSMA-PET scans can be employed at multiple disease stages, Calais concludes. 

Editor's note: Dr. Calais reports serving as a consultant or in an advisory role for Blue Earth Diagnostics, Curium Pharma, GE Healthcare, Janssen, Progenics, Telix Pharmaceuticals; he receieved honoraria from advanced accelerator applications, Progenics, Radiomedix

Jeremie Calais, MD, MSc, discusses the role of prostate-specific membrane antigen-PET imaging in metastatic-castrate resistant prostate cancer, and touches on the importance of integrating PSMA-PET imaging into community settings for clinical practice.

Dr. Calais on the Role of PSMA-PET Imaging in mCRPC

In a recent study, investigators at the University of California in Los Angeles (UCLA) and San Francisco (UCSF) have demonstrated high positive predictive value for a new imaging technique for localizing recurrent prostate cancer.

 The diagnostic test is called prostatespecific membrane antigen positron emission tomography/ computed tomography imaging, or PSMA PET/CT, and is used to help treat patients who have previously had radiation or surgery for prostate cancer. The study’s results demonstrated that this scan is effective in finding the location of a recurrence of prostate cancer cells (

Imaging is important for men who have been treated for prostate cancer because sometimes cancer cells remain in the body after surgery. This happens if not all cancer cells are removed during the surgical procedure or if some of the tumors lie beyond the prostate region. Determining the recurrent tumor locations can help for a better individualized treatment approach.

It is important for patients with signs of recurrence after initial therapy to undergo an imaging scan to find the location of the cancer cells.

To examine the effectiveness of the new imaging technique, investigators at the UCLA Jonsson Comprehensive Cancer Center and UCSF collaborated on a multicenter study to evaluate imaging with 68GA-PSMA-11, a PET scan with a gallium-labeled PSMA ligand. The team, which published its findings in 

, included Johannes Czernin, MD, and Wolfgang P. Fendler, MD, both of UCLA, and Thomas A. Hope, MD, of the UCSF.

The scan was performed on 635 patients previously treated with prostatectomy, radiation therapy, or both. Participants had a proven biochemical recurrence of cancer, defined as a prostate-specific antigen (PSA) level ≥0.2 ng/mL more than 6 weeks after prostatectomy or a PSA of ≥2 rise above nadir following radiation therapy.

The novel diagnostic test was able to detect cancer cells in 475 patients (75%) with a positive predictive value of 84% to 92%.

In a follow-up study, the UCLA team of investigators independently continued the evaluation of the PSMA PET/CT scan. Calais and colleagues, including Czernin, published findings in Lancet showing PSMA PET/CT to be more effective in finding an early recurrence of prostate cancer after surgery compared with the current standard-of-care technique, 18F-fluciclovine PET/CT.

Fluciclovine is a synthetic amino acid used as a radiotracer. Cancer cells consume more amino acids than regular cells, and this imaging technique enables doctors to identify the location of the cancer by tracking the cells that consume more of the fluciclovine.

By contrast, the PSMA imaging technique tracks protein expression levels. Prostate cancer cells overexpress PSMA in comparison with normal cells, and this imaging method can determine the location of the cancer cells by tracking these cell-surface proteins.

For the purposes of the study, investigators deidentified the scan images. These images were sent to 3 independent physician readers, each of whom read the scans 3 times. Individual readers were unaware of the conclusions reached by the others.

The results showed that the PSMA imaging was able to detect the recurrence of prostate cancer in 56% of the scans. In comparison, the fluciclovine scan was able to detect prostate cancer in 26% of the scans (OR, 4.8; 95% CI, 1.6-19.2; 

The UCLA investigative team concluded that, because of its effectiveness, PSMA imaging should be the PET imaging agent of choice for men who have prostate cancer recurrence after radical prostatectomy. The PSMA PET/CT scan continues to be investigated, beyond the clinical trials described previously.

PSMA PET/CT May Improve Radiation Therapy Outcomes

PSMA PET/CT also may have a significant role in guiding salvage radiation therapy for patients who have undergone radical prostatectomy, according to findings that Calais and colleagues, inclduing Nicholas G. Nickols, MD, PhD, of UCLA, published in the 

In June 2019, the editors of the publication cited the study as one of the best articles published by the journal in 2018. It won the Editor’s Choice Award for Best Clinical Article and was named Overall Best Article in 2018. The article has been cited more than 95 times by other study authors and provided the rationale to initiate a phase III randomized trial powered for outcome.

Beyond prostate cancer, the UCLA investigative team is testing the PSMA PET/CT imaging technique to detect the vasculature cells of multiple cancers such as pancreatic, ovarian, head and neck, lung, and breast. This is because the PSMA chemical compound binds to proteins found on the surface of vasculature cells and can be seen through nuclear imaging. In this study, patients will also undergo fibroblast activation protein inhibitor PET/CT, which can show the stromal cells surrounding the tumor lesions. Breaking up stroma and blood vessels necessary for cancer growth, may make tumors easier to treat with medication, radiation, and cell-based immunotherapy.

Fendler WP, Calais J, Eiber M, et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial. 

. 2019;5(6):856-863. doi: 10.1001/jamaoncol.2019.0096.

Calais J, Ceci F, Eiber M, et al. 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. 

. 2019;20(9):1286-1294. doi: 10.1016/S1470-2045(19)30415-2.

Calais J, Czernin J, Cao M, et al. 68Ga-PSMA-11 PET/CT Mapping of prostate cancer biochemical recurrence after radical prostatectomy in 270 patients with a PSA level of less than 1.0 ng/ml: impact on salvage radiotherapy planning. 

. 2018;59(2):230-237. doi: 10.2967/jnumed.117.201749.

Best JNM articles for 2018. J Nucl Med. 2019;60(6):16N. 

. jnm.snmjournals.org/content/60/6/16N.full.pdf+html. Accessed February 25, 2020.

The men each received a fluciclovine scan as part of their postsurgical recurrence standard-of-care treatment. They also received an additional PSMA imaging scan within 15 days before or after their fluciclovine scan.

In comparing these 2 imaging methods, UCLA researchers studied 50 patients. Each of the patients had previously undergone a radical prostatectomy in which surgeons removed the prostate gland and surrounding tissue due to cancer. Enrollment criteria included biochemical recurrence of prostate cancer with low PSA levels (<2.0 ng/mL) indicating that cancer recurrence was at an early stage.

Articles

In a recent study, investigators at UCLA and UCSF have demonstrated high positive predictive value for a new imaging technique for localizing recurrent prostate cancer.

Jeremie Calais, MD, PhD

Articles

Dr Calais on Controversies in the Treatment of Patients With Prostate Cancer

Dr. Calais on the Role of PSMA-PET Imaging in mCRPC

Novel Imaging Method Proves Effective in Detecting Prostate Cancer Recurrence