"LUMPECTOMY" FOR PROSTATE CANCER?

October 23, 2009 — A new finding has given fresh impetuous to the idea of focal therapy for prostate cancer, which focuses ablation on the index malignant lesion, not — as is the current standard — the whole gland.

The subject is discussed in a paper on the clinical implications of basic research in the October 22 issue of the New England Journal of Medicine.

"There is a lot of interest in this focal approach to treatment, because it reduces side effects," says author Hashim Uddin Ahmed, MRCS, BM, BCh, from University College Hospital in London, United Kingdom.

"It is based on the idea that management of localized prostate cancer can follow the organ preservation approach taken in the treatment of almost all other solid tumors," he writes. "In other words, ablation of only the malignant areas within the prostate, along with a margin of normal tissue, and preservation of normal prostate and surrounding structures will help reduce side effects."

Although the data are early, the focal approach appears to be comparable to the standard radical approach in terms of cancer control, and it greatly reduces the risk for "collateral damage" to tissues surrounding the prostate gland, Dr. Ahmed told Medscape Oncology in an interview.

The radical approach of ablating the whole prostate — with surgery, radiation, or cryotherapy — carries with it about a 70% risk for impotence and a 10% risk for incontinence, Dr. Ahmed pointed out.

Four trials have now been carried out in the United States with a focal approach, using cryotherapy, and the retrospective data from these suggest a 20% risk for impotence and risk for incontinence of less than 5% — in some series, no cases of incontinence were reported.

Both approaches show a cancer control of around 80% to 90%, he noted.

Data for the focal approach are still short term, with a follow-up of around 2 to 4 years after the procedure, whereas the radical approaches have been in use for much longer, so there are far more data; results for surgery go out 20 to 30 years. Also, because prostate cancer tends to progress slowly, it can take years before there is a relapse, so cancer control is measured by biopsies (with negative biopsies suggesting no cancer present) and biochemically (by prostate-specific antigen [PSA] screening), he added.

But the data so far suggest that the focal approach to prostate cancer therapy looks "very encouraging," Dr. Ahmed noted.

"It's like the difference between a mastectomy and a lumpectomy in breast cancer," he continued. "In prostate cancer, we are about 20 years behind, but the focal approach has been made possible only in the past few years; it's only now that we have the technology that can pinpoint lesions with millimeter accuracy."

Now that such technology is available, there is a growing interest in this focal approach to therapy, he said: "This is taking prostate cancer clinical researchers by storm."

Dr. Ahmed previously discussed the focal approach to therapy for prostate cancer in Nature Clinical Practice Oncology (2007;4:632-642).

The new finding that caused him to revisit the idea was published recently in Nature Medicine (2009;15:559-565). That study, conducted by Wennuan Liu, PhD, from Wake Forest University of Medicine, in Winston-Salem, North Carolina, and colleagues, under the leadership of Steve Bova, MD, from Johns Hopkins University, in Baltimore, Maryland, suggests that a single precursor cell is responsible for generating metastatic disease.

Those researchers analyzed tissue samples taken from men with prostate cancer who had died of disseminated disease and who had donated their bodies to science.

The team obtained 94 samples of malignant tissue from various metastatic sites taken from 30 men, and analyzed them with a high-resolution genome-wide survey of single-nucleotide and copy-number polymorphisms. They found that within each patient, metastases at various anatomically distinct sites originated from a single precursor cell.

"All of the metastases came from a single cancer cell in the prostate," Dr. Ahmed explained.

Unfortunately, Dr. Ahmed notes, the researchers were unable to determine where this single precursor cell came from, and if it was situated in the index lesion. These men had died from disseminated disease, and had undergone many different treatments for the prostate cancer, including androgen-deprivation therapy, which shrinks the gland and causes morphologic and histologic changes, he explained.

It is highly likely that this single precursor cell is found in the index lesion, Dr. Ahmed explained. There is accumulating evidence, including some new research from the Memorial Sloan-Kettering Center in New York City, which shows that the majority of aggressive cancer cells (more than 90%) are located in the index lesion. This is usually an aggressive high-grade tumor with a tendency to extend into the capsule, he said.

In contrast, there might be other "spots" of cancer within the prostate gland that are low grade. More than half of all men who are older than 60 years of age have these small low-grade tumors in their prostate, which might never grow to a point where they threaten health, he pointed out, so "it makes sense that small lesions don't need to be treated."

Focal therapy focuses on ablating just the index lesion, leaving the low-grade tumor spots and the rest of the prostate gland intact. At University College Hospital, Dr. Ahmed is involved in a clinical trial program, headed by Mark Emberton, FRCS, which is investigating focal therapy with high-intensity focused ultrasound. This is used to ablate the index lesion, and the men are followed closely with active surveillance and PSA tests every 3 months. A similar trial is ongoing at the University of Texas MD Anderson Cancer Center in Houston, but there, ablation of the index lesion is carried out with cryosurgery.

Currently, the main aim of focal therapy is to reduce the adverse effects of treatment, Dr. Ahmed said. But the hope is that by focusing on the index lesion, this approach will destroy the aggressive clone that goes on to metastasize and ultimately kill the patient, he added.

Dr. Ahmed has disclosed no relevant financial relationships.

N Engl J Med. 2009;361:1704-1706. Abstract