Expert Shares Insight on Role of RT, Surgery in Prostate Cancer

Johnathan Warner, MD

Following the FDA approval of high-intensity focused ultrasound (HIFU) for prostate tissue ablation, there are ongoing clinical trials attempting to determine how effective the technology can be for the treatment of patients with prostate cancer, explains Jonathan Warner, MD.

“Are there ways that we can optimize the cure rates with HIFU? When are people recurring? What are we missing when they recur? What are the true rates of complications? We do not know the answer to most of these questions,” Warner adds.

There is currently an ongoing phase II/III European trial (NCT022651590) attempting to evaluate cancer control and general overall health-related quality-of-life outcomes and effectiveness of HIFU for patients with localized prostate cancer. This trial, which is expected to be completed in 2020, is evaluating the proportion of men who are free of clinically significant prostate cancer 36 months after focal therapy with HIFU.

Researchers are exploring novel approaches with cryotherapy and focal therapy. In addition, with the implementation of the active surveillance and novel agents for more aggressive disease, the roles of surgery and radiation therapy could be changing.

OncLive: What are some of the side effects of local definitive therapies for prostate cancer?

In an interview during the 2017 OncLive^® State of the Science Summit on Genitourinary Cancers^TM, Warner, an assistant professor in the Division of Urology and Urologic Oncology, Department of Surgery, City of Hope, discussed the evolving role of surgery and radiation therapy in the treatment landscape for patients with prostate cancer.Warner: If we look at the 2 curative therapies for prostate cancer, radiation and surgery have been the long-term options available for patients. The primary side effects that come with surgery are erectile dysfunction and urinary incontinence. When a patient has surgery and they suffer from one of those consequences, the outcomes and the treatments are very predictable.

When you have radiation for prostate cancer, whether that is in the salvage setting or as a primary modality, unfortunately, the nature of the radiation creates a lot of unpredictability as far as the treatment options go.

For example, for urinary incontinence, if a patient has had an operation and the prostate is removed, many patients can be cured or improved with a male sling procedure, which is a non-manipulated device that helps them restore their continence. However, in the radiated patients, the slings are just not as successful. Only about 50% of men will have some improvement.

Another big part of my practice is with strictures after radiation therapy. Again, this can be either from a patient who has had a prostatectomy and then had to undergo salvage radiation therapy or a patient who had primary radiation therapy. This comprises about 25% of my practice. It can be a devastating problem, since sometimes we must remove the whole bladder when these complications occur. Again, the treatment options are there but they are unpredictable as far as the success rates go.

Some people are doing focal therapies for prostate cancer either with HIFU or focal cryotherapy, which is when they freeze the lesion that is found on the MRI. We are stepping into new realm of treatments that are going to develop into new complications. Firstly, with HIFU, the cure rates are not quite as good as the first 2 therapies that I mentioned. We are seeing a lot of recurrences and those patients need to face a decision about what to go through, whether that is removing the prostate or radiation therapy. Most of these patients are surgery averse, so they often go to radiation therapy. We compound the effects and the patients often have worse complications.

Are there ongoing trials with focal therapy looking to further explore the treatment?

With cryotherapy, we see a lot of fistula formations, which are holes between the rectum and the prostate that develop after cryotherapy. Those can be devastating complications with significant risks that are difficult to repair. There are trials actively ongoing. The biggest change that has happened with focal therapy is the advent of MRI. MRIs have been around for a long time, but the new protocols that are utilized have allowed us to isolate significant lesions found on prostate cancers.

What questions are the HIFU trials trying to answer?

With the introduction of active surveillance, what will be the role of surgery moving forward?

There are trials attempting to localize steam therapy to the region of prostate cancer. They are looking at focal therapy with cryotherapy, so they will freeze the area where the lesions are identified. We can use those MRIs to focus on the areas where the lesions are seen. Again, we are probably going to miss some of the cancer, but the MRI will show us the most aggressive cancers. It might not show us all of the low-grade cancers, but the low-grade cancers are not usually the ones that cause the problems. There are active trials in those areas, as well as with HIFU, since it has achieved FDA approval status.Now that it has reached FDA approval, people are trying to see how useful it will be. We do not know the answer to most of these questions. Many patients left the United States to get their treatments and have come back. We do not know what the long-term complications will be.My hope is that we will see less prostate cancer surgery and radiation. MRIs have helped us identify whether the cancer is significant, which has been useful. Genomic markers are groundbreaking. Analyzing prostate biopsy tissue and analyzing patients’ blood are ways that we are going to detect those genes that are more or less aggressive.

How do you determine when a patient should receive surgery or radiation therapy?

Is there anything else you would like to add regarding surgery for prostate cancer?

Prostate cancer, at baseline, is a slow-growing process. There is obviously the collection of patients who have an aggressive cancer and we need to figure out how to find those that need treatment versus those that can be observed. We are making headway and we have made improvements over the last several years, but there is still a long way to go. Half of my practice is devoted to radiation complications. I am clearly biased against radiation. Patients need to make this decision, but they should be well educated. The complications of radiation tend to develop years down the road. Many people do not realize that 5 or 10 years [after therapy] is when we are starting to see the complications of radiation. We need to prepare patients for that and help the younger patients understand that, if they receive radiation, there are going to be issues down the road. We need to focus our efforts on younger patients to move away from radiation. Hopefully, through education, we can make sure people understand what the consequences are.There are side effects from radiation and surgery for prostate cancer treatment, but it is important to recognize that we can treat those side effects. The first goal is curing cancer and then we can deal with any of the complications. I do not think patients should let the worry of urinary incontinence or erectile dysfunction guide their decision. We can fix those problems. It is important to focus on whether the patient needs treatment and, if they do, then we will help with the complications.