A new disease space that is gaining much more attention is the non-metastatic castration-resistant prostate cancer (nmCRPC), which are by definition, without evidence of metastatic disease using standard staging studies. As systemic therapies for patients with CRPC depend on the classification of nmCRPC vs. mCRPC, there is increasing discussion of the true nature of nmCRPC – likely these patients have micrometastases not yet identified on standard staging studies. Often with low PSA values, these patients represent a ripe opportunity for novel imaging tools such as PSMA PET/CT – as identification of low volume metastases may allow for local therapy (metastases-directed therapy) or different systemic therapies.
In this study, the authors retrospectively characterized the extent of disease using PSMA-PET in men with clinical characteristics similar to those on the SPARTAN trial1; the SPARTAN trial was a randomized clinical trial demonstrating survival benefit with apalutamide treatment in men with nmCRPC. Once the authors assessed the results of PSMA PET/CT in this population, they then compared the risk factors for M1 disease detected by PSMA-PET to those in SPARTAN.
The primary endpoint was detection rate of local/pelvic disease and distant metastatic (cM1) disease on PSMA/PET CT. PSMA PET was evaluated locally by one unblended reader and centrally by 2 blinded readers. Inter-reader variability was not significant – indeed, they were almost identical. 8825 patients from 6 high volume patients were screened and 200 patients met inclusion criteria.Full baseline characteristics of the PSMA-PET and SPARTAN patients were generally similar.
See table below for summary:
* It should be noted that PSA doubling time was not available for all patients in this study. Therefore, for patients without PSA doubling time, they were only included if they had high grade disease (Gleason 8-10). This is why there is a higher proportion of men with Gleason 8-10 disease in the study population than in SPARTAN.
In the PSMA-PET group, PSMA-PET CT detected PC in 196/200 (98%) pts! 55% had local recurrence, 54% had pelvic nodes (N1), and 55% had any extrapelvic distant metastatic disease despite negative conventional imaging. Ultimately, 24% were diagnosed with local recurrence only, 29% with oligometastatic (1-3 lesions) and 46% with polymetastatic disease.
On multivariable analysis, PSA >= 5.5 ng/mL, pN1 disease, and prior local therapy were significantly associated with M1 disease detected by PSMA-PET.
All clinically relevant subgroups of SPARTAN patients, including men with independent predictors of PSMA-PET-M1 disease, significantly benefited from APA.
Based on this very interesting, albeit retrospective analysis, men with PSMA-PET-positive CRPC (albeit negative standard staging studies) were similar to those at high-risk of developing metastases in SPARTAN. Apalutamide showed significant benefit in all clinically relevant subgroups of SPARTAN patients, including men with risk factors for distant metastases detected by PSMA-PET. Therefore, apalutamide should be considered for men negative by conventional imaging but positive by PSMA-PET (stage migration). The added value of PSMA-PET over PSADT in men with high-risk nmCRPC should be explored in prospective studies.
One of the main take home points brought up by Dr. Hadaschik was the following: since systemic therapies seem to work very well in nmCRPC and mCRPC (by conventional imaging), PSMA/PET CT may not have much of a role in this patient population – systemic therapy is the way to go. Adding additional local therapies can be explored, but the results of the PSMA/PET should not stop the patient from getting systemic therapy! He suggests its probably better utilized in the hormone-sensitive setting to identify potentially curable local recurrences – to help avoid systemic therapy!
Presented by: Boris Hadaschik, MD, University Hospital Essen
Co-authors: Manuel Weber, Amir Iravani, Michael S. Hofman, Jérémie Calais, Johannes Czernin, Harun Ilhan, Fred Saad, Eric J. Small, Matthew R. Smith, Paola M. Perez, Thomas A. Hope, Isabel Rauscher, Anil Londhe, Angela Lopez-Gitlitz, Shinta Cheng, Tobias Maurer, Ken Herrmann, Matthias Eiber, Wolfgang Fendler
Written by: Thenappan Chandrasekar, MD (Clinical Instructor, Thomas Jefferson University) (twitter: @tchandra_uromd, @JEFFUrology) at American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois