Oncotype DX is a genomic test that has been shown to predict the likelihood of distant cancer recurrence and the likelihood of chemotherapy benefit in women with early-stage, estrogen receptor-positive breast cancer that is treated with tamoxifen. The test evaluates the activity of 21 genes from a sample of the patient’s cancer to determine the patient’s Recurrence Score. The higher the Recurrence Score, the higher the risk of cancer recurrence. Oncotype DX has been added to U.S. medical guidelines for early-stage breast cancer.

The current analysis assessed how the Recurrence Score performed among women treated with the aromatase inhibitor drug Arimidex and among those with node-positive breast cancer.

The researchers collected information from 1,231 women who participated in the ATAC (Arimidex, Tamoxifen, Alone or in Combination) study. The study enrolled postmenopausal women with early, hormone receptor-positive breast cancer. Study participants received hormonal therapy with either tamoxifen or Arimidex.

The Recurrence Score (RS) predicted the risk of distant cancer recurrence among women with node-negative and node-positive breast cancer:

• Among women with node-negative breast cancer, nine-year risk of distant cancer recurrence was 4% among women with a low Recurrence Score, 12% among women with an intermediate Recurrence Score, and 25% among women with a high Recurrence Score.
• Among women with node-positive breast cancer, nine-year risk of distant cancer recurrence was 17% among women with a low Recurrence Score, 28% among women with an intermediate Recurrence Score, and 49% among women with a high Recurrence Score.

The relationship between Recurrence Score and risk of distant cancer recurrence was similar regardless of the type of hormonal therapy that the women received.

This study suggests that the Oncotype DX test provides information about risk of distant cancer recurrence in both node-negative and node-positive, hormone-receptor positive breast cancer. Furthermore, Oncotype DX was predictive of distant recurrence risk among women treated with tamoxifen as well as women treated with Arimidex.

Reference: Dowsett M, Cuzick J, Wales C et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. Journal of Clinical Oncology [early online publication]. March 8, 2010.

Early-stage prostate cancer refers to Stage I or II prostate cancer that is limited to the prostate and nearby lymph nodes and has not spread from the prostate to distant sites in the body. Men who have intermediate-risk, early-stage prostate cancer have disease that is likely to recur.

Standard therapy for early-stage prostate cancer may include surgery, radiation therapy, watchful waiting (no treatment until disease progression), and hormone therapy. Optimal treatment for early prostate cancer is still under debate, though it appears that individualized approaches may provide the best outcomes.

Though hormone therapy is often used to slow the growth of advanced prostate cancer, its use in early-stage cancer is still being evaluated. A large Phase III Radiation Therapy Oncology Group (RTOG) study involved 1,979 men with early-stage prostate cancer who had a PSA of 20 or less; 987 men received four months of hormone therapy (HRT), starting two months prior to radiation therapy, and 992 men received the standard treatment of radiation therapy alone.

After a median follow-up of 8.4 years in the HRT group and 8.1 years in the radiation-only group, 51% of patients who received HRT were still alive at 12 years compared with 46% of those who received radiation alone. The survival benefit appeared to be greatest for men with intermediate-risk disease; men with low-risk disease did not benefit from the addition of HRT. Furthermore, two years following treatment, 843 men underwent prostate biopsies. Seventy-eight percent of biopsies in the HRT group showed no cancer compared with 60% in the radiation-only group. The hormone therapy was well tolerated.

The researchers concluded that men with intermediate-risk, early-stage prostate cancer may benefit from the addition of HRT to radiation. Research will be ongoing to evaluate the risks and benefits of this treatment strategy.

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Bladder cancer is common; approximately 55,000 new cases are diagnosed in the U.S. each year. Superficial bladder cancer refers to cancer that has not spread to muscles of the bladder or nearby lymph nodes. Patients treated for superficial, or early-stage, bladder cancer have a high risk of recurrence and typically undergo routine screening with cystoscopy every three to six months. (During a cystoscopy, a physician places a lighted tube into the bladder to search for abnormal areas of tissue that indicate cancer.)

Because cystoscopy can miss some cancers, some physicians have begun to test the urine for certain cancer biomarkers in the hopes of increasing the likelihood of detecting a cancer recurrence early. However, it has been unclear whether these tests improve cancer detection.

Researchers at the University of Texas M. D. Anderson Cancer Center performed an analysis comparing the accuracy and costs of bladder cancer surveillance strategies in 200 patients with a history of bladder cancer. They compared the use of cystoscopy alone with the use of cystoscopy and several urine tests (NMP22, FISH, cytology, and NMP22 plus FISH to confirm abnormal NMP22).

They found that cystoscopy alone was the least expensive test ($7,692) and was also associated with the fewest false-positive results (two). Cystoscopy plus the urine biomarker tests grew increasingly more expensive. Cystoscopy plus FISH was the most expensive screening method ($19,111) and also resulted in the highest number of false-positive results (30). Notably, the urine tests did not appear to improve tumor detection.

The researchers concluded that cystoscopy alone is the most cost-effective method for monitoring for bladder cancer recurrence and also results in the fewest false-positive tests.

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Since the late 1980s, the primary screening tool for early detection of prostate cancer has been the prostate specific antigen (PSA) test. While this test is widely used, it remains controversial, due to both false positive and false negative test results. Produced by cells in the prostate, PSA levels in the blood tend to be elevated in men who have prostate cancer. However, not all men with prostate cancer have elevated PSA, and not all men with elevated PSA have prostate cancer. PSA levels can also become elevated as a result of noncancerous conditions of the prostate.

Men who have elevated levels of PSA are often referred for a prostate biopsy in order to determine whether prostate cancer is present. Men who have a negative first biopsy, however, are often likely to remain uncertain about their risk of prostate cancer. This is because a biopsy only samples small areas of the prostate, and it’s not uncommon for a repeat biopsy to detect cancer that was missed by the first biopsy.

PCA3 is a test that could potentially help guide decisions about the need for repeat prostate biopsy in men suspected of having prostate cancer. PCA3 (prostate cancer gene 3) is overexpressed in men with prostate cancer but not in men with noncancerous prostate problems. The PCA3 test measures PCA3 expression in a sample of urine.

In the study presented at the Genitourinary Cancers Symposium, the PCA3 test was evaluated in 1,072 men who had PSA levels between 2.5 and 10 ng/mL and a negative initial biopsy. Repeat biopsies were performed after the second and fourth year of the study.

• A higher PCA3 result indicated a greater likelihood of finding prostate cancer on a repeat prostate biopsy. Prostate cancer was diagnosed in only 6% of men with a low PCA3 score but in 57% of men with a high PCA3 score.
• PCA3 results were correlated with cancer aggressiveness: men with high-grade cancers tended to have higher PCA3 results than men with low-grade cancer.
• PCA3 results also provided information about the likelihood of a future positive biopsy: men who had high PCA3 but a negative prostate biopsy at the two-year mark were more than twice as likely to have prostate cancer detected at the four-year mark than men with low PCA3.

These results suggest that the PCA3 test provides useful information about the need for repeat prostate biopsy in men with elevated PSA.

Reference: Groskopf J, Aubin SM, Reid J et al. Validation of the PCA3 molecular urine test for predicting repeat prostate biopsy outcome in the placebo arm of the dutasteride REDUCE trial. Presented at the ASCO 2010 Genitourinary Cancers Symposium. March 5-7, 2010. San Francisco, CA. Abstract 5.

Bisphosphonates are a class of drugs used to prevent and treat osteoporosis and to reduce the risk of bone complications from bone metastases or multiple myeloma. Studies have suggested that in addition to their effects on bone, bisphosphonates may also have certain anticancer effects.

To assess whether bisphosphonates used for osteoporosis influence the risk of breast cancer, researchers conducted a study among 2,936 women with breast cancer and 2,975 women without breast cancer. All women were under the age of 70 years.

Bisphosphonates that may be used to treat osteoporosis include Fosamax® (alendronate), Actonel® (risedronate), Boniva® (ibandronate), and Reclast® (zoledronic acid).

• Compared with women who had never used bisphosphonates, women who currently used bisphosphonates were 33% less likely to develop breast cancer.
• Longer duration of bisphosphonate use was associated with a greater reduction in risk of breast cancer.
• The reduction in risk of breast cancer among bisphosphonate users appeared to be limited to women who were not obese.

The researchers concluded that bisphosphonates may be linked with a potentially important reduction in breast cancer risk.

Like most drugs, bisphosphonates carry a risk of side effects. Women who are considering bisphosphonate use to manage osteoporosis are advised to talk with their doctor about the risks and benefits.

Reference: Newcomb PA, Trentham-Dietz A, Hamptom JM. Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk. British Journal of Cancer. 2010;102:799-802.

Prostate cancer is a hormonally sensitive disease that can be controlled for long periods with androgen deprivation therapy (ADT) or castration. When prostate cancer stops responding to this treatment is it referred to as hormone refractory prostate cancer. Because hormone refractory prostate cancer can be difficult to treat, new agents and treatment approaches continue to be evaluated.

Cabazitaxel is an investigational chemotherapy drug. To evaluate cabazitaxel in the treatment of metastatic, hormone refractory prostate cancer, researchers conducted a Phase III clinical trial (the TROPIC study) among 755 men in 26 countries. All of the study participants had experienced cancer progression in spite of Taxotere-based chemotherapy.

Study participants were assigned to receive treatment with either cabazitaxal plus prednisone or mitoxantrone plus prednisone.

• Median survival was 15.1 months among men treated with cabazitaxel compared with 12.7 months among men treated with mitoxantrone.
• Men treated with cabazitaxel also fared better in terms of progression-free survival and tumor response rates.
• Men treated with cabazitaxel were more likely than men treated with mitoxantrone to develop febrile neutropenia (low white blood cell count accompanied by fever).

In a prepared statement, the lead investigator on the study noted: “There are no effective treatments available to help men with metastatic castration-resistant prostate cancer whose disease continues to grow despite standard chemotherapy, and this large study shows an unequivocal survival benefit for patients who received cabazitaxel.”

Cabazitaxel has not yet been approved by the U.S. Food and Drug Administration (FDA). The results of this study will form the basis for a submission for FDA review.

Reference: Sartor AO, Oudard S, Ozguroglu M et al. Cabazitaxel or mitoxantrone with prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: final results of a multinational phase III trial (TROPIC). Presented at the ASCO 2010 Genitourinary Cancers Symposium. March 5-7, 2010. San Francisco, CA. Abstract 9.

Multiple myeloma is a cancer of plasma cells. Plasma cells are a special type of white blood cell that are part of the body’s immune system. Plasma cells normally live in the bone marrow and make proteins, called antibodies, which circulate in the blood and help fight certain types of infections. Plasma cells also play a role in the maintenance of bone by secretion of a hormone called osteoclast activating factor, which causes the breakdown of bone. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine. These abnormal antibodies are referred to as paraproteins or monoclonal proteins in the blood (M proteins) or urine (Bence Jones protein).

Velcade is the first in a new class of anticancer agents known as proteasome inhibitors. It’s been shown to provide benefits in the treatment of multiple myeloma and mantle cell lymphoma.

The VISTA study is an international Phase III clinical trial. The study enrolled 682 newly diagnosed multiple myeloma patients who were ineligible for stem cell transplantation. Patients were assigned to receive treatment with melphalan and prednisone (MP) alone or in combination with Velcade. Patients have now been followed for a median of 36.7 months.

Compared with patients treated with MP alone, patients treated with MP plus Velcade had a 35% reduction in risk of death. The addition of Velcade to MP also delayed cancer progression and improved treatment response rate.

The sustained overall survival benefit provided by Velcade has now been added to the Velcade label. Information has also been added to the label about dosing recommendations for patients with liver impairment.

Reference: Millennium: The Takeda Oncology Company. FDA Approves Addition of Sustained Overall Survival Benefit to Label for Velcade® (Bortezomib) for Injection for Patients with Previously Untreated Multiple Myeloma. Accessed March 4, 2010.

Human papillomaviruses consist of more than 100 different viruses. Some types of HPV cause warts on the hands or feet; others cause genital warts; and some have been linked with cancer, most notably cervical cancer. The types of HPV most commonly linked with cervical cancer are HPV16 and HPV18, but several other high-risk types contribute to cancer as well.

The types of HPV that cause cervical cancer or genital warts are transmitted sexually. HPV infection is extremely common and generally occurs soon after an individual becomes sexually active. Although most infections resolve on their own, some persist and can lead to precancerous or cancerous changes to the cervix, vulva, vagina, penis, and anus. HPV infection has also been linked to certain cancers of the head and neck.

Recognition of the link between HPV and cervical cancer led to the development of vaccines designed to prevent infection with certain high-risk types of HPV.

Currently, there are two vaccines approved for the prevention of HPV 16 and 18: Gardasil® and Cervarix®. Gardasil also protects against HPV 6 and 11, which are associated with most types of genital warts. The vaccines are recommended for girls as young as age 9 and up to age 26. Little data exists, however, to determine whether older women will benefit from the vaccines.

A study of more than 9,000 Costa Rican women ages 19 to 97 evaluated the patterns of HPV infection as women age. The researchers found that the rate of newly detected infections declined with age—from 35% in women ages 18-25 to 13.5% in women over the age of 42. In both younger and older women, new infections typically cleared up without treatment within two years. They found that new infections typically did not progress to worse disease in older women.

Based on their findings, the researchers concluded that HPV vaccination was not likely to be beneficial for older women. The vaccinations are used to prevent new infections, and older women are not getting many new infections.

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The kidneys are each filled with tiny tubules that clean and filter the blood; this process removes waste and makes urine. Renal cell cancer (RCC) is a malignancy involving these tubules of the kidney. Surgery is the mainstay of treatment for kidney cancer, as the cancer is typically resistant to radiation and chemotherapy. Historically, surgical treatment of RCC consisted of a radical nephrectomy, which involves removal of the entire kidney, local lymph nodes, and any cancer in the area surrounding the kidney. The trend in the surgical management of RCC, however, is to perform less aggressive surgery when possible.

Cryoablation is a minimally invasive technique that uses extremely cold temperatures to “freeze” small cancers. In patients with cancer that is less than or equal to 5.0 cm in diameter, cryoablation appears to be a promising approach for removing the cancer. Two recent studies evaluated two different methods of cryoablation.

Researchers from the Cleveland Clinic evaluated CT-Nav®, a stereotactic surgical navigation system that delivers cryoablation and radiation to a tumor via a cryoprobe. This reduces the radiation exposure compared with conventional radiation treatment. This was a prospective pilot study designed to evaluate the feasibility, safety, and accuracy of the system. The system was used to cryoablate 13 tumors in 10 patients. The mean tumor size was 2.2 cm; mean operation time was 155 minutes; and mean length of hospital stay was 9.5 hours. There were no complications. The researchers concluded that this method offers potential for patients with kidney cancer.

Researchers from the University of Southern California evaluated laparoscopic renal cryoablation in 80 patients with renal tumors; the mean tumor size was 2.3 cm. All patients were treated by a single surgeon and then followed for a minimum of five years. At five years overall survival was 84%, and progression-free survival was 81%. At ten years overall survival was 51%, and progression-free survival was 78%. The researchers concluded that this as an effective treatment for select patients.

The results of these two studies indicate that cryoablation may start to play a larger role in the surgical treatment of kidney cancer.

References:

2 Aron M, KAmoi K, Remer E, et al. Laparoscopic renal cryoablation: 8-year, single-surgeon outcomes. Journal of Urology. 2010; 183: 889-895.

Radical prostatectomy refers to the surgical removal of the entire prostate and some surrounding tissue. Prostatectomy may be performed using traditional open surgery, in which the surgeon makes a single, long incision; or through a laparoscopic procedure (sometimes called minimally invasive surgery), in which several small incisions are made. During laparoscopy, the surgeon inserts a small video camera through one of the incisions in order to see inside the abdomen. In a variant of laparoscopic surgery known as robotic-assisted laparoscopic surgery, the surgeon sits at a console near the operating table and performs the surgery by controlling robotic arms that hold the surgical instruments.

Laparoscopic surgery has been perceived as a less invasive procedure that may preserve erectile function; however, there has been little research and no data to substantiate this claim.

A population-based study included 5,923 men aged 66 or older with localized prostate cancer. All of the men underwent radical prostatectomy between 2003 and 2005; 18% of these procedures were performed laparoscopically. After adjusting for patient and tumor characteristics, the researchers found that there were no differences in the rate of complications between the two surgeries nor were there differences in postoperative treatment with radiation or hormone therapy.

The laparoscopic procedure was associated with a 35% shorter hospital stay and a 26% lower rate of bladder neck and urethral obstruction. Patients who underwent surgery from surgeons who performed a higher volume of laparoscopic procedures tended to have shorter hospital stays and reduced chance of genitourinary and bowel complications.

The researchers concluded that laparoscopic and open prostatectomy produce similar results and similar rates of complications. Therefore, men considering prostatectomy must weigh the risks and benefits of each procedure to make an informed, personal decision.

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