American Society of Clinical Oncology – Genitourinary Cancers Symposium, Orlando, Florida, 17-19 February 2011

New studies on the screening and treatment of genitourinary cancers were highlighted at the 4^th annual GU Cancers meeting sponsored by ASCO. This brief report looks at three of those studies. 

Screening reduces risk of prostate cancer death for men with low initial PSA values

A landmark prostate cancer screening study of middle-aged and elderly men that included repeat visits showed that an initial prostate-specific antigen (PSA) score of 3.0ng/ml appears to be an appropriate minimum cut-off level to determine the need for biopsy.

Few men in the study with low first-time PSAs below 3.0 developed prostate cancer and died from the disease.

Researchers also found that within this group of low-risk men, the higher the initial PSA, the greater the risk of developing prostate cancer and more aggressive disease, and of dying from prostate cancer.

“Our results strengthen the justification of the use of PSA in risk stratification for screening purposes,” said lead author Dr Meelan Bul (Department of Urology, Erasmus University Medical Centre, Rotterdam, The Netherlands).

“This means that we can possibly avoid unnecessary testing, diagnosis and treatment of less aggressive disease, with the accompanying side-effects, by focusing biopsies and other follow-up in men with higher initial PSAs above 3.0.”

This investigation was part of the larger European Randomised Study of Screening for Prostate Cancer. Researchers analysed both incidence of and deaths from prostate cancer among 42,376 men between ages 55 and 74, randomised to either screening or a control arm.

They found 15,758 (79%) of the men had an initial PSA under 3.0. Between 1993 and 2008, 915 of those men were diagnosed with prostate cancer – with a median follow up of 11 years – with only 23 deaths.

Of the 915 diagnosed, 182 were detected between screenings, often indicating a faster-moving disease, and overall, 169 (1.1%) were determined to be aggressive prostate cancers.

Overall, prostate cancer incidence and deaths increased significantly with higher PSA levels:

-         only 129 men (1.8%) of 7,126 men with PSA scores below 1.0 were eventually diagnosed with prostate cancer, with only three deaths (0.04%)

-         of the 6,156 men with PSA scores between 1.0 and 1.9, 415 (6.7%) developed prostate cancer, with 11 deaths (0.18%)

-         The researchers found 2,476 men with PSA levels between 2.0 and 2.9, with 371 cases of prostate cancer (15.7%) and nine deaths (0.36%).

Dr Bul commented: “The 3.0 score appears to be an appropriate threshold for the study because approximately 80% of the men ages 55 to 74 years had a PSA under 3.0, with few deaths from prostate cancer. At the same time, we still found a group of men with aggressive prostate cancer and we need improved methods of detecting aggressive disease.”

The investigators suggested that future research focus on improving the detection of aggressive prostate cancers, including better risk stratification methods and new molecular and genetic markers.

Only the most experienced surgeons should be allowed to perform robot-assisted prostate repairs

Because the learning curve for robotic-assisted laparoscopic radical prostatectomy (RALP) operations is so protracted, it’s a procedure that should only be performed by surgeons who see large volumes of patients.

That was the main conclusion reached by New York investigators who found in a retrospective analysis of the results of nearly 3,800 procedures showed that it took more than 1,600 prostate cancer surgeries for surgeons to become proficient at the RALP procedure and be able to remove the cancerous prostate consistently with its edges clear of cancer.

RALP is a relatively new technology that has several advantages over typical laparoscopic surgery, which uses awkward “chopstick-like” instruments. RALP provides surgeons with 3-dimensional vision, improved magnification, hand tremor filtering, and a range of motion similar to the human wrist.

“The robotic platform has been shown to take less training time to learn to safely perform prostate cancer surgery compared to its open and laparoscopic surgery counterparts, but we see that becoming expert at the robotic operation takes much longer than just simply developing a base level of competence,” said

Lead author Dr Prasanna Sooriakumaran (Visiting Fellow in Urology, Weill Cornell Medical College, New York) commented: “This research shows that optimising patient outcomes in terms of positive margin rates takes much more experience. In this regard the operation is more difficult than previously thought.”

He and his colleagues reviewed the surgical results of 3,794 patients who underwent RALP over a six-year period between 2003 and 2009 in procedures performed by three surgeons from the University of Pennsylvania, Karolinska Institute and Cornell University.

The researchers determined mean overall positive surgical margin rates (PSM) rates and operation lengths for each surgeon at intervals of every 50 operations. The investigators found that the PSM rates for all patients continued to improve with increasing surgeon experience. It took more than 1,600 cases to achieve a PSM rate of less than 10%, which is considered a standard goal for such surgeries.

“Even for those who do hundreds of cases per year, it takes a long time to get to the stage where they are getting the best possible cancer control results,” Dr. Sooriakumaran said. “Our results show that it is possible to get good cancer cure rates and low surgical margins with this operation, but it takes a significant amount of experience.”

Intermittent versus continuous androgen suppression after radical therapy – survival just as good, quality of life may be better

New data suggest that intermittent androgen suppression (IAS) is equivalent to continuous androgen deprivation (CAD) in terms of overall survival (OS) in men with prostate-specific antigen (PSA) recurrence after radical radiotherapy (RRT) – raising the hope that IAS will offer a new therapeutic option with improved quality of life (QoL).

Details of this Intergroup randomised phase III trial, which included many patients from the UK, were presented by Dr Lawrence Klotz (Sunnybrook Medical Sciences Centre, Toronto, Canada).

Eligible men had rising PSA >3.0ng/ml >1 year post RRT for localised prostate cancer. IAS was delivered for eight months in each cycle, restarting when PSA reached >10ng/ml off-treatment.

An independent adjudicator recommended halting the trial after a planned interim analysis demonstrated that a pre-specified threshold for non-inferiority was reached.

A total of 1,386 patients were randomised to IAS or CAD arms, with a median follow-up of 6.9 years. IAS patients completed a median of 2 x 8 month cycles.

A total of 524 deaths were recorded (268 on IAS vs 256 on CAD). The IAS arm had more disease related (122 vs 97) and fewer unrelated (134 vs 146) deaths.

Median OS was 8.8 vs 9.1 years on IAS and CAD arms, respectively (hazard ratio [HR] 1.02, p=0.009). Time to hazard ratio was statistically significantly improved in the IAS arm (HR 0.80, p=0.024).

IAS patients had reduced hot flashes, but otherwise there was no evidence of differences in adverse events (AEs), including myocardial events or osteoporotic fractures.