It's hardly ever that a study results in fundamental changes in how cancer patients are treated. But latest research is doing just that for some men with prostate cancer that recurs after initial treatment.
Recurrence after treatment
The first sign of reoccurrence is normally a rise within the blood level of prostate-specific antigen (PSA). PSA should drop to zero after surgical removal of the prostate, and shut to zero after radiation therapy. Prostate cancer cells release PSA, so if levels rise again after this initial treatment, latest tumors are more likely to form within the body. This is named biochemical reoccurrence, since the newly developing tumors are still too small to be seen on conventional imaging scans.
Doctors often treat biochemical recurrences with hormonal therapy, drugs that stop the body from making testosterone (a hormone that fuels prostate cancer growth). But the outcomes of a giant clinical trial suggest there may be a greater way.
Study Methodology and Results
During the studyCalled the EMBARK Phase 3 clinical trial, investigators enrolled 1,068 men whose PSA levels had doubled inside nine months of initial treatment. When PSA rises this quickly, men are vulnerable to developing cancer more quickly.
The men were randomly divided into three groups: one was treated with a hormonal therapy called leuprolide, given by injection every 12 weeks; The second group was treated with leuprolide together with a day by day oral dose of enzalutamide, a drug that removes testosterone from its cell receptor. A 3rd group was self-treated with day by day enzalutamide.
Investigators already knew from earlier studies that enzalutamide delayed progression and prolonged survival in men with metastatic prostate cancer. With this latest study, they hypothesized. First Using this drug can have similar advantages for men with biochemical reoccurrence.
This assumption proved correct. The men were followed for less than five years after treatment was accomplished. And in accordance with the outcomes, a lot of the men treated with enzalutamide remained cancer-free. Specifically, 87.5% of men who received the mix treatment—and 80% of men treated with enzalutamide alone—survived from metastatic cancer, compared with 71.4% of men who received leuprolide alone.
Enzalutamide treatment was also simpler in stopping further rise in PSA. Overall, 97.4% of men who received combination therapy and 88.9% of men who took enzalutamide alone avoided PSA rise, compared with 70% of men treated with leuprolide. If the PSA was below 0.2 ng/ml at 36 weeks, men could stop treatment altogether. More (as much as 90%) of men treated with enzalutamide discontinued treatment for a period of as much as 20 months.
Enzalutamide treatment was well tolerated. The commonest side effect was mild to moderate nipple pain and breast enlargement. Most of the lads in all three groups are still alive, and EMBARK investigators are following them to see if treatment-related survival differences show up over time.
Observations and comments.
Based on the EMBARK results, Dr. Neil Shore, director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina, and a co-author of the study, concluded that enzalutamide treatment “is now the standard of care for high-risk biochemical recurrences.” Whether enzalutamide treatment ought to be combined with leuprolide is a choice men could make in consultation with their doctor.
An necessary point is that doctors now have a greater approach to detect metastatic prostate cancer that was not available when EMBARK began. Cancer cells have high levels of a protein called prostate membrane-specific antigen (PSMA) that shows up on special imaging scans. PSMA-based imaging methods can reveal small metastatic tumors within the body that were previously unseen. In such cases, patients who may once have been diagnosed with biochemical reoccurrence at the moment are known to have metastatic cancer. And because doctors can now see these tumors, they will treat them directly with surgery or radiation — and potentially achieve a cure.
Still, Dr. Stephen Friedland, lead EMBARK investigator and urologist at Cedars-Sinai Medical Center in Los Angeles and the Durham VA Medical Center in Durham, North Carolina, says the study's findings still apply. If PSMA results are negative at the same time as PSA continues to rise,” then EMBARK shows that systemic therapy [using enzalutamide with or without hormonal therapy] continues to be the most effective option,” he says.
If PSMA results show only just a few metastatic tumors (called oligometastatic prostate cancer), these tumors could be treated with surgery or radiation, and possibly hormonal therapy. And if PSMA shows widespread metastatic cancer throughout the body, then “metastasis-directed therapy is no longer an option, and hormonal therapy with enzalutamide is the best option to delay progression as shown in EMBARK, ” says Dr. Friedland.