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Multimodal therapy eliminates detectable disease in early metastatic prostate cancer
Aggressive multimodal therapy appeared to eliminate all detectable disease among certain patients with early metastatic prostate cancer, according to study results.
“The endpoint of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states, and to shift the paradigm from palliation to cure,” Matthew J. O'Shaughnessy, MD, PhD, member of the urology service in the department of surgery at Memorial Sloan Kettering Cancer Center, and colleagues wrote.
O’Shaughnessy and colleagues assessed the feasibility of multimodal therapy — comprised of androgen deprivation therapy, surgery and radiation therapy — for eliminating all detectable disease among 20 men with early metastatic prostate cancer. Five patients had extra-pelvic lymph nodal disease and 15 patients had bone disease.
All patients received continual androgen deprivation therapy unless they achieved undetectable PSA after 6 months. Patients also underwent radical prostatectomy with pelvic lymph node dissection, retroperitoneal lymph node dissection when needed, and radiation therapy to sites of bone metastases.
Undetectable PSA after testosterone recovery served as the primary endpoint.
Researchers reported that 95% of patients achieved undetectable PSA with multimodal treatment.
HemOnc Today spoke with O’Shaughnessy about the study, the potential implications of these findings and the questions that still must be answered in subsequent research.
Question: How did this study come about?
Answer: Improving outcomes among men with metastatic prostate cancer has been one of our goals for a long time. Historically, testing new therapies for prostate cancer typically requires studies with large numbers of patients. At times, these studies do not provide meaningful results. This pilot study was designed to evaluate a new strategy that we thought would be a better and more efficient way to test new treatments for men with prostate cancer.
Q: How did you conduct the study?
A: We examined 20 patients with low-volume metastatic prostate cancer treated with a multimodal therapy. The goal of the therapy was to treat all apparent sites of disease. Androgen deprivation therapy was used for 8 months, in addition to surgery — specifically, radical prostatectomy — and lymph node dissection. In some cases, a retroperitoneal lymph node dissection was required, with the goal of dissecting all gross disease of the pelvis and any other areas of lymph node involvement. Patients with bone metastasis received radiation to the bone lesions in most cases. The idea was to complete all of these interventions within an 8-month period, then stop all treatment — including androgen deprivation therapy — and allow for testosterone recovery. The final endpoint we were looking for was undetectable PSA at the point of testosterone recovery, roughly 20 months following the start of treatment. This endpoint represents no evidence of disease.
Q: What did you find?
A: We found that 20% of patients met the primary endpoint of undetectable PSA with a recovered serum testosterone. This is really the first report, to our knowledge, to show complete elimination of disease among patients with metastatic prostate cancer. Our results support the hypothesis that multimodal treatment eliminates all detectable disease in some patients.
Q: What are the clinical implications of your findings?
A: This allows us to establish a new paradigm in the way that we look at studying new treatments for metastatic prostate cancer. Multimodal treatment directed toward all gross disease was critical to getting the endpoint of undetectable PSA. As each treatment was successively added, more patients reached an undetectable PSA during the study timeline. The other key point is that this is a short-term, 20-month endpoint after starting treatment. This really helps us to set an expected benchmark for future studies and to know what we can expect an undetectable PSA rate to be.
Q: What are the next research steps?
A: We are now moving forward with a larger phase 2 trial with the intent of comparing treatment combinations, using the multimodal approach that we developed in this pilot trial. I hope that, because of the short-term endpoint, we should be able to compare and prioritize treatment regimens in a relatively efficient manner with a relatively small number of patients and identify the most promising treatment combinations. After this, we can scale-up these treatment combinations for large-scale trials. We anticipate the follow-up trial to be initiated shortly.
Q: Does this approach truly represent a cure, a potential of a cure or a first step toward improving out comes for these patients?
A: Cure can only be established with time. It is an important first step, but it will require larger studies with longer follow-up time. With this approach, I think we will be able to assess this. – by Jennifer Southall
Reference:
O’Shaughnessy MJ, et al. Urology. 2017;doi:10.1016/j.urology.2016.10.044.
For more information:
Matthew J. O’Shaughnessy, MD, PhD, can be reached at Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: oshaughm@mskcc.org.
Disclosure: Grants from the NIH/NCI supported this study. O’Shaughnessy reports no relevant financial disclosures.