Focal or tissue preserving therapy has become a topic of considerable interest among urologists and in recent years has been called a new paradigm in the treatment of prostate cancer, offering another treatment option designed to balance treatment effectiveness and quality of life.

Today, prostate cancer is recognized as the second leading cause of cancer death in men in Western Europe and the United States. More than 670,000 men are diagnosed with prostate cancer worldwide every year. It is the second most common cancer in men after lung cancer.

In Europe, nearly 225,000 cases are diagnosed each year. In the United States, each year 240,000 cases are reported. Arround the world, the highest incidence rates are in the United States and Sweden and the lowest rates are observed in China and India. The extremely high rate in the United States (125 per 100,000) is more than twice the reported rate in the United Kingdom (52 per 100,000).

Results of a roundtable of international prostate cancer experts reviewing focal technologies and the latest research evaluating focal lesion diagnosis and treatment were published in the current issue of the Winter 2012 issue of theEuropean Urological Review.

Focal therapy
Building on the success of tissue preserving therapy to treat other cancers (breast, renal, bladder and rectal), focal therapy has been proposed as a means of bridging the gap between radical prostatectomy and active surveillance for treatment of prostate cancer. Results of large-scale studies, including the European Randomized Study of Screening for Prostate Cancer (ERSPC) and Prostate Cancer Intervention Versus Observation Trial (PIVOT), suggest that prostate cancer has been over diagnosed and over treated with minimal impact on overall prostate cancer mortality across all risk groups. According to several panelists, clinicians must reconsider treatment strategies and whether focal therapy can help reduce the side effects of treatment while treating those cancer lesions that are likely to cause prostate cancer-specific mortality if left untreated.

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Patient selection and the use of advanced diagnostics were called out as critical to the evolving treatment paradigm and the ability for focal therapy to be established as a suitable alternative to whole gland prostate cancer treatment. According to the Panel, results on recent studies investigating the use of pre-biopsy mpMRI and MRI-Ultrasound registration have shown promise to better localize and characterize lesions. This not only has potential for improved accuracy of focal treatments, but may also improve diagnostic sampling strategies for prostate cancer. Fewer, and better, biopsies could be performed on suspicious lesions, with potentially increased diagnostic rates of clinically significant cancer, and reduced rates for over-diagnosis of clinically insignificant disease.

The roundtable was moderated by Mark Schoenberg, MD, of the James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Maryland.

“The field of prostate cancer treatment is undergoing dramatic change as physicians scrutinize the impact of historical practice patterns, particularly those related to whole gland therapy, disease-specific survival and quality of life. As research on individual patient risk stratification and the use of advanced imaging and modern prostate biopsy techniques progresses, focal therapy for prostate cancer has emerged as an important topic for discussion and research,” Schoenberg noted. “I’m pleased that this Roundtable was able to spark a lively discussion among leading experts and investigators in focal therapy to explore how new diagnostic and therapeutic technologies may be integrated into the broader field of prostate cancer care.”

Surgery or radiotherapy
The majority of men treated for prostate cancer are treated with surgery or radiotherapy, which involve treating the whole prostate. Both cause damage to the surrounding non-cancerous tissue and can lead to substantial side effects such as urinary incontinence and impotence. The goal of focal therapy is to offer an alternative to men who value genito-urinary function and quality of life, allowing each patient and their physician to balance the risk and clinical benefit of individual treatment options.

Rapid heat
High intensity focused ultrasound (HIFU) is a therapy that destroys targeted tissue with rapid heat elevation. HIFU concentrates high frequency ultrasound waves (similar to a magnifying glass) into an area the size of a grain of rice. At that location, or focal point, the temperature rapidly rises to almost 90 degrees Celsius (195 degrees Fahrenheit). Tissue at the focal point, including cancerous tissue, is destroyed. HIFU uses non-ionizing energy, so the procedure can be repeated, if necessary. HIFU is being studied around the world to treat a wide variety of cancers and soft tissue diseases.

The Sonablate? 500 is approved for investigational use within the U.S. and is being studied for the treatment of prostate cancer in clinical trials in the U.S. The FDA has made no decision as to the safety or efficacy of the Sonablate? 500 for the treatment of prostate cancer. Currently, the device is available for the treatment of prostate cancer outside the U.S. in more than 30 countries.

Other trials
In an unrelated study, researchers showed that focal therapy for a highly selected population with prostate canceris feasible and had an acceptable morbidity with <2% major complications.

This study included 106 patients, median age 66.5 yr (interquartile range [IQR]): 61-73), who had a prostate hemiablation; 50 patients (47%) had cryotherapy, 23 patients (22%) had VTP, 21 patients (20%) received HIFU, and 12 patients (11%) had brachytherapy.

The median prostate-specific antigen (PSA) level was 6.1 ng/ml (IQR: 5-8.1), all the patients had a biopsy Gleason score of 6, and the median prostate weight was 43g (IQR: 33-55). The median International Prostate Symptom Score was 6 (IQR: 3-10), and the median International Index of Erectile Function score was 20 (IQR: 15-23). After treatment, the median PSA at 3, 6, and 12 mo was 3.1 2.9, and 2.7 ng/ml (IQR: 2-5.1, 1.1-4.7, and 1-4.4), respectively. Thirteen percent of the patients experienced treatment-related complications. There were 11 minor medical complications (10 grade 1 complications and 1 grade 2 complication), 2 grade 3 complications, and no grade 4 or higher complications.

For more information:
– Bomers J, Dickinson L, F?tterer JJ, Barentsz J, Katz A, Klotz L, Schoenberg M,Ukimura O, et al. Roundtable Discussion ? Focal Therapy for Prostate Cancer. European Urological Review, 2012;7(2):101-5
– Barret E, Ahallal Y, Sanchez-Salas R, Galiano M, Cosset JM, Validire P, et al. Morbidity of Focal Therapy in the Treatment of Localized Prostate Cancer. Eur Urol. 2012Dec 13. doi:pii: S0302-2838(12)01473-X. 10.1016/j.eururo.2012.11.057. [Epub ahead of print]

Clinical trials
NCT00007644 – Prostate Cancer Intervention Versus Observation Trial (PIVOT):A Randomized Trial Comparing Radical Prostatectomy Versus Palliative Expectant Management for the Treatment of Clinically Loca
lized Prostate Cancer.

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