We recently published a commentary in European Urology on the utility of PSMA/PET scans. PSMA/PET is a new imaging tool used for prostate cancer, which is ultra-sensitive. It can pick up cancer spread that is not always visible on conventional scans (CT or MRI).
Picking up more cancer lesions might be good, since it means earlier, less aggressive forms of cancers can be found and treated. Unfortunately medicine is not that easy. In our paper we discuss three reasons how despite greater sensitivity, staging with PSMA/PET might end up having a net negative effect on patients. Shown nicely in this Figure
Denying patients therapy, from which they benefit
New studies suggest that local radiotherapy (usually only reserved for early stages of prostate cancer, without cancer spread) actually can help some patients that have a low number of metastases. But PSMA complicates this. The same patient staged with PSMA/PET will have a higher number of metastases, then had he been staged with a conventional scan. The trials showing a benefit of local therapy for patients with a low number of metastases, relied on conventional staging. This means that someone who is staged as having a “high metastatic burden” by a PSMA/PET scan could still profit from local therapy, but would be denied this therapy based on his PSMA/PET results.
Exposing patients to therapy they might not need
Next PSMA will definitely upstage some patients and result in chemo-hormonal therapy, which we don’t know benefits them.
All the benchmark trials for prostate cancer were conducted in an era without PSMA/PET and relied on conventional scans. Their results cannot be assumed to directly apply to patients staged with PSMA/PET. It is possible that some patients deemed to have cancer spread by PSMA/PET might not necessarily benefit from chemotherapy and would be exposed to all its added toxicities for no reason.
Encouraging experimental therapies
Some docs have fallen in love with radiating oligo-metastatic lesions. This seduction of focused local therapy for cancer manifestation outside the prostate is getting increasingly popular. PSMA/PET can be used to find lesions to target within such approaches. But the evidence supporting radiating these lesions is still weak. We still do not know how much patients profit from these therapies. The increased use of PSMA/PET might motivate providers to implement such experimental approaches in places where they otherwise would not have.
Conclusion
In conclusion we can say, while sensitivity is a desirable treat, the clinical context in which it is used matters. When indiscriminately applied in a setting where most therapies were developed using less sensitive tools, it may not enhance outcomes, but could, at times, worsen them.
It is not asking too much that costly technologies demonstrate in randomized fashion non just that they are more sensitive, but their routine use improves outcomes.
Read the full editorial here.
Each new , more-sensitive, test will "up-stage" a proportion of patients. This"stage migration" was referred to as the "Will Rogers phenomenon" in a classic NEJM paper four decades or so ago. An interesting spin off is that, if treatment protocols, stage for stage, remain constant, the "stage migration" results in an improved outcome at every stage, while of course the overall outcome for the population is unaffected