ASCO 2017: How Advances in Molecular Imaging Have Changed Our Understanding of State and Stage of the Disease

Chicago, IL ( Dr. Juergen Gschwend, from Munich, Germany, provided an excellent summary of the advances in molecular imaging, specifically PSMA PET scan, in prostate cancer (PCa) management. As Germany has been a leader in this technology, his experience with the technology provided an important context for the discussion.

His main talking points for the talk today are as follows:
1) Targets and Tracers for PET imaging
2) Enhanced local detection of prostate cancer (PCa) by PSMA-PET
3) Primary lymph node (LN) and bone staging
4) Detection of recurrent PCa
5) Local therapy by radioguided surgery

Molecular Targets for PCa PET Imaging
Traditionally, the most common targets of PET imaging had been fludeoxyglucose (18F FDG) and choline 11C, but they demonstrated low sensitivity (49.2%) for LN staging.1 However, the identification of Prostate specific membrane antigen (PSMA), a cell-surface protein overexpressed on most PCa’s, has changed management of PCa. It should be noted, though, that the main limitation throughout all its utilization is that approximately 10% of PCa does not express PSMA.

While there are many PSMA targeting agents utilized, they all share a common ligand-binding domain that binds to PSMA. The physiologic distribution of PSMA is also important to understand: it localizes to the salivary glands, liver, spleen, small intestines, and particularly to the kidneys and bladder (excreted in urine). 

Enhanced local detection of prostate cancer (PCa) by PSMA-PET
While this is not common, some groups have evaluated the use of PSMA-PET scans for identification of localized prostate cancer. Combined with MRI, Eiger et al2 were able to improve the detection rate from 66% using multiparametric MRI (mpMRI) alone to 98% using mpMRI and PSMA-PET (AUC 0.88). This technology can also be used with fusion biopsies to better target lesions. However, further work is needed before this can be utilized in practice.

Primary lymph node (LN) and bone staging
Certain centers internationally are now using PSMA-PET for primary staging after new diagnosis of high-risk prostate cancer. A prospective assessment by Maurer et al3 in 130 patients with intermediate to high risk localized PCa who subsequently underwent radical prostatectomy and extended lymph node dissection (RP+ePLND) found LN metastases in 30% of patients, and only 8.4% of patients had LN metastases that were PSMA-PET negative. They found the sensitivity and specificity to be 75% and 98.8%, respectively; compared to CT/MRI, which had Sens/Spec of 41% and 85%, respectively. Pyka et al found superior identification of bone metastases in PSMA-PET scan vs. traditional nuclear medicine bone scans as well.

While it appears to be superior to standard imaging, it may still miss lesions < 5 mm. Also, there have not yet been studies to establish any long-term oncologic differences with this management. However, Dr. Gschwend believes it may become the new standard as it may be a “one-stop shop” for staging.

Detection of recurrent PCa
In patients with evidence of recurrent, PSMA PET may be able to identify disease recurrence at much lower PSA thresholds than traditional imaging and even other PET modalities (such as Choline PET). A study by Maurer and Elber et al5 demonstrated that PSMA-PET combined with either CT scan or MRI were equivalent in identifying small volume recurrent disease, even in PSA ranges as low as 0.2-0.5. It was superior to Choline PET at PSA values between 1-2 (91.9% vs. 43%). 

As such, this may represent a phase of diagnostics for biochemically recurrent prostate cancer.

Local therapy by radioguided surgery
However, after identification, what is the best way to manage potentially low-volume oligometastatic patients, especially with just lymph node disease? He describes their experience with radioguided surgery similar to sentinel node dissection in breast cancer. They give the patients a tracer (indium or technetium) 24 hours prior to surgery and then complete a node dissection using a gamma probe intraoperatively. After showing videos of the technique, he noted that 29/30 PSMA-PET identified hotspots were detected during surgery, and sens/specificity were 92.3% and 93.5% respectively. More impressive were the durable PSA response rates for a median 1-year follow-up. While more follow-up is needed, this may represent a new field of therapeutics for oligometastatic disease.

He didn’t mention these, but there are also radiolabeled medications, such as Lutetium, that can be tagged to PSMA to achieve potentially similar responses, even in larger volume disease. 

The take home messages:
Molecular staging of prostate cancer has already changed clinical practice and guidelines in Germany. PSMA-PET has evolved as a valuable imaging tool in primary staging, evaluation for recurrent disease, and monitoring of metastatic disease.

Presented By: Juergen E. Gschwend, MD, PhD, Technical University of Munich, Munich, Germany

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Toronto, Ontario, Canada
Twitter: @tchandra_uromd

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA

1. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Evangelista L, Guttilla A, Zattoni F, Muzzio PC, Zattoni F.
Eur Urol. 2013 Jun;63(6):1040-8. doi: 10.1016/j.eururo.2012.09.039. Epub 2012 Sep 25. Review.

2. (68)Ga-PSMA PET/MR with multimodality image analysis for primary prostate cancer. Eiber M, Nekolla SG, Maurer T, Weirich G, Wester HJ, Schwaiger M. Abdom Imaging. 2015 Aug;40(6):1769-71. doi: 10.1007/s00261-014-0301-z.

3. Diagnostic Efficacy of (68)Gallium-PSMA Positron Emission Tomography Compared to Conventional Imaging for Lymph Node Staging of 130 Consecutive Patients with Intermediate to High Risk Prostate Cancer. Maurer T, Gschwend JE, Rauscher I, Souvatzoglou M, Haller B, Weirich G, Wester HJ, Heck M, Kübler H, Beer AJ, Schwaiger M, Eiber M. J Urol. 2016 May;195(5):1436-43. doi: 10.1016/j.juro.2015.12.025. Epub 2015 Dec 9.

4. Pyka T, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016 Nov;43(12):2114-2121. Epub 2016 Jun 12.

5. Eiber M, et al. Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy. J Nucl Med. 2015 May;56(5):668-74. doi: 10.2967/jnumed.115.154153. Epub 2015 Mar 19.
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