Ask the Experts – Douglas M. Dahl, MD

Question 1. What presentation(s) did you find particularly informative or enlightening?

Answer
Several papers on surgical management of lymph nodes during prostate cancer treatment. Raskin et al (MP54-17) showed higher-than-previously reported lymphedema and resulting negative quality of life in patients undergoing extended pelvic lymphadenectomy. Gupta et al (MP22-14) conducted an excellent phase 2 trial of ADT and chemotherapy followed by radical prostatectomy and adjuvant radiation if needed for men with oligometastatic prostate cancer, with promising early results. Martin Gleave [of the Vancouver Prostate Centre in Canada] gave a superb Ramon Guiteras Lecture on the challenges of newer anti-androgen therapies and the tendency over time for prostate cancer to become fiercely independent of androgens. This may result in neuroendocrine differentiation, which is highly lethal phenotype.

Question 2. Did you note any studies that provide insight into improving prostate cancer screening and risk stratification?

Answer
There were some important studies dealing with how to screen more effectively and wisely so we can find more early-stage serious prostate cancer and perform fewer biopsies and interventions in men without serious prostate cancer. MRI and biomarkers have become important tools in this regard. A number of urinary biomarkers show promise in discriminating between serious prostate cancer and insignificant cancers. Biomarkers that are useful are the PHI [prostate health index] test in the screening population and the Decipher test for helping stratify men post prostatectomy for further therapy. The 4K assay, which is a serum test, is useful but expensive and I think impractical to use because of the involved ordering process. Tests that don’t require a lot of filling out of forms, are easier to order, and are not expensive are going to be the ones that are the most useful and will catch on most quickly. I think we’re getting more clarity on the use of these tools. Johnson et al (MP30-04) showed MRI may miss significant lesions and emphasized that systematic biopsy is still indicated. Preston et al (MP24-03) looked at genetic variants in PSA levels. They found that baseline PSA, after adjusting for genetic risk score, modestly improved prediction of total and aggressive prostate cancer, particularly in patients with moderately elevated PSA. These findings may help avoid biopsy in men who run a higher PSA due to genetics.

Question 3. What do you see as the key to developing an optimal screening approach?

Answer
Nobody has come up with an algorithm that really makes sense. What is needed is lower cost and effective screening modalities, perhaps involving the use of biomarkers early on to help decide who gets an MRI, which is very expensive and many insurance companies still do not want to pay for it as an early test in evaluating men with an elevated PSA.

Question 4. Would you like to offer any thoughts on where the management of high-risk and advanced prostate cancer is headed?

Answer
We are seeing more and more advanced prostate cancer, possibly because not enough screening was being done 5 years ago because of the push against screening. Studies presented at the meeting show clearly that the new antiandrogen agents can be used effectively at an earlier stage of cancer progression. We’ve known for 60 years that androgens were important in prostate cancer development and progression, and a lot of studies have shown that these new antiandrogens really do make a big difference. But big questions remain. For example, for patients with high-risk prostate cancer, do we use the drugs before primary radiation or surgical treatment or as adjuvant treatment? Studies addressing these questions need to be done.

Question 5. Any revelations about active surveillance?

Answer
Active surveillance has become accepted in a very short time. It took a while for physicians to become comfortable with this management approach. Now, there’s clearly a very substantial percentage of men with prostate cancer who are being managed with active surveillance. Lots of papers presented here report that this is safe.

Question 6. What technologies are on the horizon that could change prostate cancer management?

Answer
One of the other things that I think is going to really shake things up is the new PSMA-based PET scans, which is an expensive imaging modality. A number of studies at this meeting looked at this. Five years ago, we would just make assumptions about whether patients had locally recurrent disease. PSMA-based PET makes it possible to detect metastatic disease far more clearly. Probably a lot more people probably had metastatic disease than what we knew about with the previous imaging capabilities. That’s going to rewrite a lot of the studies, too.