Over five years ago, a small group of luminaries in the prostate cancer (PCa) world issued a critique of rising PSA as a trigger for prostate cancer intervention when patients are on active surveillance (AS).[i] The co-authors include Patrick Walsh (father of the nerve-sparing prostatectomy), Alan Partin (credited with inventing the PSA blood test), Jonathan Epstein (from Johns Hopkins, arguably one of the most famous PCa pathologists in the world) and others. They followed 290 men on AS from 1994-2008, and follow-up included DRE and PSA metrics twice annually, and a yearly surveillance biopsy. (Personal comment: I wonder how they enforced the annual biopsy, since even well-intentioned patients tend to become less compliant over the years?)
The team reported that based on biopsy-demonstrated PCa progression, 102 men (35%) developed progression at an average of 2.9 years follow-up. They found no association between PSA velocity or doubling time and the upgraded Gleason scores from the follow-up biopsies. Because the blood serum tests were not reliable for predicting adverse pathology, the authors recommended that annual surveillance biopsies be continued for men on AS. While that seems logical, I can only imagine that patients would wish for a missing alternative that could replace an unpleasant and often inaccurate repeat biopsy.
A much more recent study from Denmark examined the factors that triggered a decision to come off AS and have a prostatectomy, and the correlation between those factors and the actual surgical findings (histopathology). [ii] The team’s research involved 229 AS patients, of whom 68 went off AS based on at least one of the following triggering factors:
- Disease progression on rebiopsy
- Short PSA doubling time
- Increase in tumor category.
The team noted that those whose post-RP histopathology revealed Gleason > 7 (3+4 or greater) were “considered to have achieved a potential survival gain from the procedure (timely RP).” They found that PSA doubling time was negatively associated with timely RP, and increase in tumor category showed no correlation at all. They concluded that the progression criteria employed in their AS program showed a poor relationship with what histopathology revealed, and that only progression on rebiopsy was positively associated with final histopathology.
This brings us back to the question, Is repeat annual biopsy the best way to determine when to go off AS and seek treatment? Is something missing?
The Sperling Prostate Center is part of the international trend toward the use of multiparametric MRI (mpMRI) to monitor AS patients, in conjunction with serum biomarkers. It’s the link that’s been missing. The advantages of this system include:
- Annual serum and/or urine-based biomarkers are a relatively inexpensive way to monitor tumor activity.
- If a rise in PSA, together with free PSA and total PSA values, communicates a possible increase in tumor activity, it triggers a 3T mpMRI—not a biopsy!
- Results from imaging may trigger a biopsy, but it will be an MRI-guided targeted biopsy—fewer needles, greater accuracy.
- If treatment is needed, and the patient qualifies for a focal therapy, a successful middle ground between AS and radical treatment has been achieved.
In short, 3TmpMRI in conjunction with biomarkers is a more useful pathway to biopsy and/or intervention because it is kinder on the patient and more strategic in treatment decisions.
[i] Ross A, Loeb S, Landis P, Partin A, Epstein J, Kettermann A, Feng Z, Carter HB, Walsh P. Prostate-specific antigen kinetics during follow-up are an unreliable trigger for intervention in a prostate cancer surveillance program. J Clin Oncol. 2010;28:2810-16.
[ii] Thomsen FB, Berg KD, Iversen P, Brasso K. Poor association between the progression criteria in active surveillance and subsequent histopathological findings following radical prostatectomy. Scand J Urol. 2015 Apr 28:1-6. [Epub ahead of print]