The bladder is a hollow organ located in the pelvis. Its primary function is to store urine. The bladder has a muscular wall that allows it to get larger and smaller as urine is stored or emptied. Bladder cancer is diagnosed in roughly 50,000 men and 17,000 women annually in the United States.

Patients with T2-T4 bladder cancer have cancer that is considered non-metastatic but that has invaded the muscle wall. Historically, these cancers have been treated with radical cystectomy, which refers to complete surgical removal of the bladder. More recently, however, several studies have supported the bladder preservation measures offered by treatment with combined modality therapy (CMT), which consists of transurethral resection bladder tumor (TURBT), radiation therapy, and chemotherapy.

Researchers from Massachusetts General Hospital presented 15-year outcomes from a study that involved 348 patients with cT2-T4aNxMO bladder cancer who were treated with TURBT, radiation, and chemotherapy. Seventy-two percent of patients had a complete response to induction therapy. Rates of disease-free survival were 64% at five years, 59% at 10 years, and 57% at 15 years. Overall survival rates were 52% at five years, 35% at 10 years, and 22% at 15 years. The survival rates were slightly higher among the subset of patients who had Stage T2 cancer than they were among those with T3-T4 disease. Neoadjuvant therapy did not appear to improve outcomes.

The researchers concluded that approximately 70% of patients treated with CMT achieved complete response and that long-term survival rates were comparable to those achieved with more radical surgery.

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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.

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.

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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Current treatment options for prostate cancer include watchful waiting, surgery, chemotherapy, radiation, or hormonal therapy. Hormonal therapy is designed to block testosterone from stimulating the growth of hormone-dependent types of prostate cancer. Some hormonal therapies (such as surgical removal of the testes or use of medications such as leuteinizing hormone releasing hormone [LHRH] analogues) inhibit production of testosterone by the testes. Other therapies, such as the antiandrogen drugs, block the activity of testosterone.

Some prostate cancers become resistant to standard hormonal therapy and require a different treatment approach; this condition is known as hormone refractory prostate cancer. Because hormone refractory prostate cancer can be difficult to treat, new agents and treatment approaches continue to be evaluated.

Abiraterone is an experimental drug that is taken orally. It blocks the production of androgens (male hormones such as testosterone) not only by the testes but also by the adrenal glands.

To evaluate the safety and effectiveness of abiraterone in the treatment of men with hormone refractory prostate cancer, researchers have conducted Phase II clinical trials.

One of the studies enrolled 47 men with hormone refractory prostate cancer that had previously been treated with Taxotere® (docetaxel)-based chemotherapy.[1] All were treated with abiraterone.

• PSA declines of 30% or more were observed in 68% of patients.
• PSA declines of 50% or more were observed in 51% of patients.
• PSA declines of 90% or more were observed in 15% of patients.
• The median time to PSA progression was 169 days.
• 41% of 27 patients with circulating tumor cells had a significant decline following treatment with abiraterone.

The other study enrolled 58 men with progressive, metastatic, hormone refractory prostate cancer that had previously been treated with Taxotere.[2] Study participants were treated with abiraterone plus prednisone.

• 36% of patients experienced a greater than 50% decline in PSA levels.
• A partial reduction in detectable cancer occurred in 18% of patients.
• Median time to disease progression was 169 days.
• Treatment reduced circulating tumor cells.

The results of these studies suggest that abiraterone is active against advanced, hormone-refractory prostate cancer. Phase III clinical trials of abiraterone are underway.

References:

[2] Danila DC, Morris MJ, de Bone JS. Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. Journal of Clinical Oncology [early online publication]. February 16, 2010.

Prostatectomy for localized prostate cancer can be performed by retropubic radical prostatectomy, laparoscopic prostatectomy, and more recently, by laparoscopic robotic techniques. In all of these procedures there is a learning curve; rates of cancer recurrence tend to decrease as a surgeon gains more experience.  It’s possible, however, that other factors may also contribute to variability in surgical outcomes.

Researchers involved in the current study looked at the outcomes of 7,725 men with clinically localized prostate cancer treated with open radical prostatectomy in four major U.S. medical centers between 1987 and 2003. Patients were treated by one of 54 surgeons.

Outcomes varied even among surgeons with a similar degree of experience:

• Among experienced surgeons, seven had a five-year prostate cancer recurrence rate of less than 10% and five had a prostate cancer recurrence rate of more than 25%.
• Variability in outcomes among surgeons with similar levels of experience persisted even after accounting for possible differences in patient populations.

These results suggest that in addition to surgeon experience, other factors also influence prostatectomy outcomes. The researchers who conducted the current study note that it will be important to determine and characterize these other factors that affect surgical outcomes.

Reference: Bianco FJ, Vickers AJ, Cronin AM, et al. Variations among experienced surgeons in cancer control after open radical prostatectomy. Journal of Urology. 2010;183:977-983.

Previous research has indicated that Chinese herbal products containing aristolochic acid (such as Guan Mu Tong) have been linked to renal failure and urinary tract cancer.[2] In 2003, Taiwan banned products that contained the herb.

Researchers conducted a population-based, case-control study in Taiwan in order to examine the association between the herb and subsequent development of urinary tract cancer. The study included 4,594 patients with urinary tract cancer (newly diagnosed between 2001 and 2002) and 174,701 control subjects selected from the National Health Insurance reimbursement database.

The results of the study indicated that there is a linear dose-response relationship between consumption of the herb and risk for urinary tract cancer. A prescription of more than 60 grams of the herb was associated with an increased risk and the risk continued to increase with increased dosage. The risk was independent of arsenic exposure, which has also been linked to urinary cancer.

The researchers concluded that consumption of herbs containing aristolochic acid placed patients at risk of developing urinary tract cancer. Ingestion of the herb accounted for 3% of all urinary tract cancers diagnosed between 2001 and 2002 in Taiwan.

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Metastatic cancer refers to cancer that has spread to distant sites in the body. Several types of cancer—including prostate cancer—have a tendency to spread to the bone. Bone metastases can lead to serious problems such as fracture and spinal cord compression, and may require treatment with surgery or radiation therapy.

Bisphosphonate drugs such as Zometa are commonly used to reduce the risk of complications from bone metastases. Researchers continue, however, to explore new approaches to treatment.

Denosumab is an investigational drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab has shown promising results in the management of patients with bone metastases as well as the management of bone loss due to cancer treatment.

To directly compare denosumab to Zometa among prostate cancer patients with bone metastases, researchers conducted a Phase III clinical trial. The study enrolled 1,901 patients with metastatic, hormone-refractory prostate cancer. Study participants were assigned to receive either denosumab or Zometa.

The objective of the study was to determine whether the occurrence of bone complications (“skeletal related events”) differed between the two study groups. The bone complications that were evaluated were fracture, radiation to the bone, surgery to the bone, and spinal cord compression.

• Patients treated with denosumab remained free of bone complications longer than patients treated with Zometa. Denosumab also reduced the rate of multiple bone complications.
• Overall survival and time to cancer progression were similar among patients treated with Zometa and patients treated with denosumab.
• Rates of adverse events were generally similar in the two study groups. Osteonecrosis of the jaw (an uncommon but serious side effect) occurred in 22 patients treated with denosumab and 12 patients treated with Zometa.

The results of this study suggest that denosumab may be more effective than Zometa at delaying or preventing skeletal complications in prostate cancer patients with bone metastases. Full results from this study will be submitted for presentation at an upcoming medical meeting.

Reference:

Amgen News Release. Denosumab demonstrated superiority over Zometa in pivotal phase 3 head-to-head trial in prostate cancer patients with bone metastases. Available at: http://www.amgen.com/media/media_pr_detail.jsp?releaseID=1385163 Accessed February 9, 2010.