Table of Contents  

Schatzl: Focal ablation of prostate cancer

Introduction

Prostate cancer (PCa) is the second most common form of cancer in men worldwide.1 With the increasing incidence of localized disease, minimally invasive treatment options for those deemed unsuitable for open surgery have become a focus of research and innovation. The current approaches to treatment (surgery, external irradiation treatment and brachytherapy) are the gold standard but are associated with important side-effects.2 Schröder et al.3 report that 1410 men have to be screened and 48 men have to be diagnosed to prevent one PCa-related death over an period of 9 years.2 The effects of ovvertreatment are also not negligible, with a survival benefit at 15 years of only 1% among a prostate-specific antigen (PSA)-screened population.3

In the last 15 years, these minimally invasive treatment options for localized PCa have been studied not only in men deemed unfit for surgical treatment but also in those who may be wary of the potential side-effects of radical prostatectomy, such as erectile dysfunction and incontinence.2,4 Potential alternative treatments include cryoablation, three-dimensional conformal radiotherapy and brachytherapy.2 Furthermore, active surveillance has been accepted as an alternative to active treatment, although Cooperberg et al.5 reported that only 10% of patients who are considered appropriate for active surveillance actually opt for this management.

Treatment options

There are few focal treatment options for PCa, with only high-intensity focused ultrasonography (HIFU) or cryoablation described in the literature; however, research has been limited by the relatively small number of patients.68 In comparison, treatment of the whole prostate gland has been well documented. Chapelon et al.9 reported that HIFU induced coagulation necrosis and can destroy Dunning R3327 PCa cells in rats. In 1995, Madersbacher et al.10,11 described the effects of HIFU in 10 cases of localized PCa and reported the effectiveness of coagulation necrosis through histological examination. Moreover, HIFU treatment of other tissues, such as benign prostate tissue, testicular tumours and kidney tumours, resulted in coagulation necrosis. Recently, Uchida et al.12 examined 181 men suffering from PCa who were treated by HIFU with the Sonoblate 500 device™ (Focus Surgery, Indianapolis, IN, USA). However, long-term studies of focal ablation are rare.68

The European Association of Urology (EAU) Guidelines describe HIFU of the prostate as an experimental treatment.2 Critics of focal ablation argue that, since 80% of prostate tumours are multifocal,13 the utility of HIFU for diagnosis and treatment is limited. Ahmed et al.8 reported that 23% of patients showed evidence of cancer after focal ablation and 8% were found to have clinically significant disease according to the Epstein criteria. In contrast, we treated all patients with a recurrent form of the disease with repeat HIFU of the entire prostate gland. Bahn et al.14 reported that, in a study of 70 men, 17% had a recurrent form of the disease 1 year after focal cryoablation: 1.4% at an ipsilateral site and 16% at a contralateral site.14 However, in that study, 31% of treated men refused a rebiopsy, which limits the authors’ conclusions.14

Ahmed et al.8 suggest two different strategies for HIFU: disease control and cancer cure. Whereas the disease control strategies treat only clinically significant lesions, cancer cures strategies treat all cancerous lesions.13 The authors recommend controlling the PSA levels for 3 months, obtaining a biopsy of the untreated area after 2–3 years and using multiparametric magnetic resonance imaging (MRI).15 However, these hypotheses are limited by the lack of valid criteria for follow-up. The American Society for Radiation Oncology (ASTRO) criteria are valid for radiation therapy, but are not approved for HIFU or cryoablation.

Many new HIFU devices have recently been developed; however, there are few studies with sufficient long-term follow-up. Thuroff et al.16 reported 1.47 HIFU sessions per patient, or a retreatment rate of nearly 50%, in a European long-term multicentre study employing the Ablatherm system (EDAP TMS, Lyon, France). Blana et al.17 described 1.17 sessions per patient in a study of 146 patients, with 21 patients receiving two treatments and two patients receiving three treatments. Uchida et al.18 reported a retreatment rate of 34% in men without neoadjuvant androgen suppression and of 31% in men with androgen suppression treated with the Sonoblate 500 system.18

The increasing number of cryoablation and HIFU treatments in the last 10 years confirms the considerable demand for minimally invasive treatment for localized PCa.19 Data are available for follow-up for an average of 5–7 years for cryotherapy. The most recently developed devices are associated with lower complication rates than earlier technologies, with the exception of an observed rise in erectile dysfunction. Aus et al.19 reported an incontinence rate of 4.4% following cryoablation using the most recent generation of cryomachines, compared with 2–27% using older technology.19 However, the rate of erectile dysfunction is very high, at 80–87%, using new technology compared with using the older equipment, for which there are limited data.

Following treatment of the whole gland, rates of erectile dysfunction range from 25% to 61%12,1719 and Poissonier et al.20 noted an impotence rate of 39% without the nerve-sparing procedure.20 Uchida et al.18 observed an erectile dysfunction rate of 9%,12 whereas Ahmed et al.15 reported no changes in the 15-question International Index of Erectile Function score at 6 and 12 months following hemiablation.8

Ahmed and Emberton15 found that the International Prostate Symptom score decreased from 22 to 12 after 1 year. It has been reported that control biopsy is preferable to MRI, after 6 or 12 months, since the sensitivity of T2-weighted sequences for PCa ranges from 37% to 96% and the sensitivity ranges from 21% to 67%.2123 Nogueira et al.23 reported that the sensitivity of PCa detection with transrectal MRI was between 2% and 20% and the sensitivity ranged from 91% to 95%, which suggested that transrectal MRI is not sufficient to identify small tumours for local treatment.23 Trivedi et al.24 detailed the limitations for MRI, such as detection rate and costs, in a cost–benefit analysis.24

Using the ASTRO criteria, in which three consecutive rises of PSA above the PSA nadir suggests treatment failure, nearly 90% of patients were disease free 7 years after treatment; however, using a fixed cut-off level of > 0.5 ng/ml, the rate decreased to nearly 65%.12 Therefore, a definition for the biochemical disease-free survival following minimally invasive treatment is required.

Other focal ablations include focal laser ablation and focal photodynamic therapy. The number of treatments currently available is very low and the follow-up period very short.25 Focal ablation of PCa is a interesting treatment option for low-risk PCa, but there are not many opportunities for focal ablation and the patient experience is often negative. In addition, a definition of biochemical disease-free survival following minimally invasive treatment is required for the future.

References

1. 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC. CancerBase No10. Lyon, France: International Agency of Research on Cancer; 2010.

2. 

Heidenreich A, Bellmunt J, Bolla M, et al. European Association of Urology. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol 2011; 59:61–71. http://dx.doi.org/10.1016/j.eururo.2010.10.039

3. 

Schröder FH, Hugosson J, Roobol MJ et al. Screening and prostate cancer mortality in a randomized European study. N Engl J Med 2009; 360:1320–8. http://dx.doi.org/10.1056/NEJMoa0810084

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Parker C, Muston D, Melia J, Moss S, Dearnaley D. A model of the natural history of screen-dedected prostate cancer and the effect of radical treatment on the overall survival. Br J Cancer 2006; 94:1361–8. http://dx.doi.org/10.1038/sj.bjc.6603105

5. 

Cooperberg MR, Broering JM, Kantoff PW, Caroll PR. Contemporary trends in low risk prostate cancer: risk assessment and treatment. J Urol 2007; 178:14–19. http://dx.doi.org/10.1016/j.juro.2007.03.135

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Muto S, Yoshii T, Saito K, Kamiyama Y, Ide H, Horie S. Focal therapy with high-intensity-focused ultrasound in the treatment of localized prostate cancer. Jpn J Clin Oncol 2008; 38:192–9.

7. 

Truesdale MD, Cheetham PJ, Hruby GW, et al. An evaluation of patient selection criteria on predicting progression-free survival after primary focal unilateral nerve-sparing cryoablation for prostate cancer: recommendations for follow up. Cancer J 2010; 16:544–9. http://dx.doi.org/10.1097/PPO.0b013e3181f84639

8. 

Ahmed HU, Freman A, Kirkham A, et al. Focal ablation for localised prostate cancer: a phase I/II Trial. J Urol 2011; 185:1246–55. http://dx.doi.org/10.1016/j.juro.2010.11.079

9. 

Chapelon JY, Ribault M, Vernier F, Souchon R, Gelet A. Treatment of localised prostate cancer with transrectal high intensity focused ultrasound. Eur J Ultrasound 1999; 9:31–8. http://dx.doi.org/10.1016/S0929-8266(99)00005-1

10. 

Madersbacher S, Pedevilla M, Vingers L, Susani M, Marberger M. Effect of high-intensity focused ultrasound on human prostate cancer in vivo. Cancer Res 1995; 55:3346–51.

11. 

Madersbacher S, Schatzl G, Djavan B, Stulnig T, Marberger M. Long-term outcome of transrectal high-intensity focused ultrasound therapy for benign prostatic hyperplasia. Eur Urol 2000; 37:687–94. http://dx.doi.org/10.1159/000020219

12. 

Uchida T, Ohkusa H, Nagata Y, Hyodo T, Satoh T, Irie A. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int 2006; 97:56–61. http://dx.doi.org/10.1111/j.1464-410X.2006.05864.x

13. 

Stamey TA, Freiha FS, McNeal JE, Redwine EA, Whittemore AS, Schmid HP. Locallised prostate cancer: relationship of tumor volume to clinical significance for treatment prostate cancer. Cancer 1993; 71:933–8. http://dx.doi.org/10.1002/1097-0142(19930201)71:3+<933::AID-CNCR2820711408>3.0.CO;2-L

14. 

Bahn D, de Castro Abreu AL, Gill I, et al. Focal cryotherapy for clinically unilateral, low-intermediate risk prostate cancer in 73 men with a median follow up of 3.7 years. Eur Urol 2012; 62:55–63. http://dx.doi.org/10.1016/j.eururo.2012.03.006

15. 

Ahmed HU, Emberton M. Benchmarks for success in focal ablation of prostate cancer: cure or control? World J Urol 2010; 28:577–82. http://dx.doi.org/10.1007/s00345-010-0590-y

16. 

Thuroff S, Chaussy C, Vallancien G, et al. High- intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol 2003; 17:673–7. http://dx.doi.org/10.1089/089277903322518699

17. 

Blana A, Rogenhofer S, Ganzer R, Wild PJ, Wieland WF, Walter B. Morbidity associated with repeated transrectal high-intensity focused ultrasound treatment of localized prostate cancer. World J Urol 2006; 24:585–90. http://dx.doi.org/10.1007/s00345-006-0107-x

18. 

Uchida T, Ohkusa H, Yamashita H, et al. Five years experience of transrectal high intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Int J Urol 2006; 13:228–33. http://dx.doi.org/10.1111/j.1442-2042.2006.01272.x

19. 

Aus G. Current status of HIFU and cryotherapy in prostate cancer – a review. Eur Urol 2006; 50:927–34. http://dx.doi.org/10.1016/j.eururo.2006.07.011

20. 

Poissonnier L, Chapelon JY, Rouviere O, et al. Control of prostate cancer by transrectal HIFU in 227 patients. Eur Urol 2007; 51:381–7. http://dx.doi.org/10.1016/j.eururo.2006.04.012

21. 

Kirham AP, Emberton M, Allen C. How good is MRI at dedecting and chracterising cancer within the prostate? Eur Urol 2006; 50:1163–74. http://dx.doi.org/10.1016/j.eururo.2006.06.025

22. 

Wu J, Gonzalgo ML. Use of magnetic resonance imaging to accurately detect and stage prostate cancer: the hype and the hope. J Urol 2011; 186:1756–7.

23. 

Nogueira L, Wang L, Fine S, et al. Focal treatment or observation of prostate cancer: pretreamtent accuracy of transrectal ultrasound biopsy and T2 weighted MRI. Urology 2010; 75:472–7. http://dx.doi.org/10.1016/j.urology.2009.04.061

24. 

Trivedi H, Turbey B, Rastinehad AR, et al. Use of patient specific MRI based prostate mold for validation of multiparametric MRI in localisation of prostate cancer. Urology 2012; 79:233–9. http://dx.doi.org/10.1016/j.urology.2011.10.002

25. 

Zaak D, Stroka R. Höppner M et al. Photodynamic therapy by means of 5 ALA induced protoporphyrin IX in human prostate cancer: preliminary results. Med Laser Appl 2003; 18:91–5. http://dx.doi.org/10.1078/1615-1615-00092





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