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'Biochemical recurrence' can be problematic

By Dr. V. Upender Rao
Published February 19, 2007

An increase in PSA values after radical surgery or primary radiation therapy for prostate cancer, without any overt signs and symptoms or evidence of recurrent cancer on imaging studies, is called "biochemical recurrence."

If the primary treatment was surgery, salvage radiation is offered; if radiation was the primary treatment, further radiation or surgical intervention can be problematic. The likelihood of a successful treatment outcome after "biochemical recurrence" is small and dependent on several tumor-related factors, some of which are listed below.

Charles R. Pound and Stephen J. Freedland found the following risk factors for increased rates of metastasis and death from prostate cancer in men who experience "biochemical recurrence" after radical prostatectomy:

-PSA elevation within three years of surgery.

-Doubling of the PSA value in less than 10 months.

-Gleeson score of 8 to 10.

-Others found positive lymph nodes and seminal vesicle involvement at initial surgery to negate any benefit from salvage radiation therapy.

An estimated 50,000 new cases of "biochemical recurrences" are diagnosed annually in the United States alone. Given the paucity of reliable treatments for this condition, new therapeutic options are urgently required.

In the February issue of the Mayo Clinic Proceedings, Janet R. Waczak, RN, and Michael A. Carducci, MD, of the Sidney Kimmel Cancer Center at Johns Hopkins University discussed the role of targeted biological agents in the management of patients with "biochemical recurrence" after radical surgery or primary radiation therapy.

They mentioned the following biological agents, which are in various phases of testing, and commented on their reported mechanisms of action:

-Revlamid acts by direct anti tumor effect and by rendering the microenvironment inhospitable for the cancer cells. It also disrupts the blood supply to the tumor (antiangeogenesis) and modulates and directs the immune system against the cancer.

-Lapatinib inhibits the Epidermal Growth Factor Receptor and ErbB2 tyrosine kinase activity. Both these provide pro growth signals to the tumor. Lapatnib interferes with these signals and curtails tumor growth.

-ATN-224 inhibits tumor progression, disrupts blood supply to the tumor (antiangeogenesis) and induces apoptosis (programmed tumor cell death) by interfering with the copper-zinc metabolism and lowering systemic copper levels.

-Bevacizumab (Avastin) is a monoclonal antibody that retards tumor growth by inhibiting the vascular endothelial growth factor. Avastin is already approved by the FDA and is being used in oncology clinics across the country for the treatment of breast, lung and colon cancers.

-Other immune modulating strategies such as tumor vaccines are also being tested against "biochemical recurrence" of prostate cancer.

In 2006, there were 234,460 new cases of prostate cancer and 27,350 deaths attributed to it. It is the most frequently diagnosed malignancy in U.S. men, accounting for 33 percent of all newly diagnosed cancers and for 9 percent of all cancer-related deaths.

Since the introduction of PSA screening and aggressive multiple directed biopsy techniques, the number of new cases of prostate cancer has increased dramatically. Additionally, alteration in the biopsy criteria for cancer grading has shifted more patients into the higher Gleeson scores and into the confines of eligibility of radical surgery and radiation.

When primary surgery and/or radiation fail, surgical or chemical castration is undertaken and continued until failure. Subsequently, taxotere-based chemotherapy, which is known to improve survival, is administered. Such aggressive treatments are justified in symptomatic patients but not for "biochemical recurrence" only.

The uncertainty and anxiety surrounding the diagnosis of "biochemical recurrence" and a lack of standard, structured care plan is a cause of concern for both the physician and patient alike. The various biologicals discussed above could offer a reasonably well tolerated and a brand new way of treating prostate cancer. Of course, they have to be validated in prospective randomized clinical trials before they are incorporated into routine practice.

V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified February 18, 2007, 21:22:10]