Focal Therapy in the Management of Localized Prostate Cancer BJUIBJU INTERNATIONAL Carvell T

2010 THE AUTHORS; BJU INTERNATIONAL 2010 BJU INTERNATIONAL Mini Reviews FOCAL THERAPY IN LOCALIZED PROSTATE CANCER NGUYEN and JONES Focal therapy in the management of localized prostate cancer BJUIBJU INTERNATIONAL Carvell T. Nguyen and J. Stephen Jones Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA Accepted for publication 1 October 2010 OBJECTIVES What’s known on the subject? and What does the study add? Focal therapy, which includes cryotherapy and high-intensity focused ultrasound,is a • To assess the rationale, efficacy, and nascent and somewhat controversial field in the management of prostate cancer. The morbidity of various methods of achieving current review presents the rationale, indications and potential role for focal therapy in focal prostatic ablation. patients withlocalized prostate cancer. • To determine the current role of focal therapy in the management of localized prostate cancer. RESULTS AND CONCLUSIONS • Until we have the ability to identify patients reliably with truly focal disease and METHODS • Focal ablative methods allow targeted predict their natural history, focal therapy destruction of prostatic tissue while limiting cannot be considered to be the definitive • We performed a literature review of focal the morbidity associated with whole-gland therapy for localized prostate cancer. therapy in prostate cancer, with an emphasis therapy. on more established methods such as • Local cancer control after focal therapy KEYWORDS cryoablation and high-intensity focused appears promising but does not approach ultrasound. that of established whole-gland therapies. focal therapy, cryoablation, prostate cancer INTRODUCTION Investigators of the Prostate, Lung, As such, there has been recent interest in Colorectal and Ovarian screening trial found organ-sparing therapy for controlling local The advent of PSA testing more than two no significant difference in prostate cancer cancer that eschews the invasiveness, decades ago has improved the early death rates between men who were screened morbidity and costs of traditional detection of prostate cancer, leading to and those who were not [2], while the intervention with RP or RT. Limiting treatment more men being diagnosed and treated. A European Randomized Study of Screening effect to only the portion of the gland with stage migration has also been observed, for Prostate Cancer reported a 20% disease is a capability unique to thermal such that the majority of men are now reduction in the mortality rate of screened ablative technologies such as cryoablation diagnosed with organ-confined disease [1]. men [3]. Indeed, given that the majority of and high-intensity focused ultrasound (HIFU). Such patients can be managed with men diagnosed with prostate cancer will not These therapies are still novel (and even definitive therapy, in the form of whole- die of their disease [4], there is concern that considered experimental by some) when gland treatment represented by radical screening has led to overdetection and compared with RP and RT in the management prostatectomy (RP) and radiation therapy overtreatment. According to recent estimates of prostate cancer. This review will assess (RT), or active surveillance (with deferred in the literature, approximately 1 million the potential of focal cryotherapy and HIFU treatment). However, defining the optimal men have been subjected to overdiagnosis in the management of clinically localized management of this patient population and overtreatment during the PSA era, prostate cancer by offering a critical review of remains difficult, largely because of the lack unnecessarily exposing them to treatment- the indications, efficacy and limitations of of randomized trials directly comparing the related side effects and financial costs [5]. each. efficacy and morbidity of the various Unfortunately, current screening methods treatment options. lack the ability to predict tumour biology and the natural history of a given patient’s DEFINING FOCAL THERAPY Interestingly, there is some controversy cancer. Because we cannot distinguish the regarding whether the increased detection tumours that will progress and cause Interestingly, current modes of delivering and treatment of prostate cancer have mortality from those that will likely not energy-based focal therapy have up until now translated into a definitive survival or cause any harm (i.e. clinically insignificant), been used as minimally invasive ways of mortality benefit for men with screen- rational application of treatment or treating the whole gland in prostate cancer. detected cancer. Interim data from two long- surveillance can be quite difficult, often Only in the last several years has the term screening studies were published in leading to an all-or-nothing approach that is technology of thermal ablation been applied 2009 and revealed conflicting results. not suited to every patient. in a focal or subtotal manner in an attempt to © 2011 THE AUTHORS 1362 BJU INTERNATIONAL © 2011 BJU INTERNATIONAL | 107, 1362–1368 | doi:10.1111/j.1464-410X.2010.09975.x FOCAL THERAPY IN LOCALIZED PROSTATE CANCER control localized disease and limit morbidity. spurred increased interest in organ-sparing IDENTIFYING PATIENTS WITH Based on the current literature, there is no approaches to treating prostate cancer, which FOCAL DISEASE consensus on what ‘focal’ means. Some are particularly suited to cases of unifocal advocates have attempted to treat only areas or unilateral disease. Advocacy of focal The multifocal nature of prostate cancer was of known cancer. Others have administered therapy in prostate cancer is attributable known even before the PSA era, with hemispheric treatment of the involved side, to its lower morbidity and more rapid approximately 80% of prostate cancer while others have treated the entire gland convalescence compared with RP or RT and to showing multiple lesions and/or bilateral with the exception of the contralateral the fact that it still offers a proactive cancer [11,12]. Because it remains difficult to neurovascular bundle. Because of the approach for patients and clinicians who do discern cases of clinically insignificant relatively novel status of focal therapy in not favour the inaction of surveillance. multifocal disease, appropriate use of focal prostate cancer, data on these options However, in order for focal therapy to be therapy requires the ability to identify those are limited but will be considered in this accepted as a viable treatment alternative, it men with unifocal or unilateral disease. review. should not compromise local cancer control Contemporary data from modern biopsy and by failing to eradicate secondary lesions of imaging techniques are analysed in the Techniques of focal therapy in prostate cancer unknown malignant potential elsewhere in present paper to see if any of these generally involve thermal ablation of the the gland. techniques can facilitate this task. tumour. Established ablative technologies include cryoablation and HIFU and achieve Predicting preoperatively whether a patient Tumours are more likely to be multifocal when tumour destruction by inducing extremes of has unifocal cancer, unilateral cancer or biopsies are diagonally positive or horizontally temperature within the targeted tissue. clinically insignificant multifocal prostate positive than in those that are vertically Cryoablation supercools lesions to cancer remains a challenge, even with positive (relative to the transverse plane), temperatures <−40 °C using liquid nitrogen- today’s improved imaging and biopsy which is logical because such findings based probes (generally applied techniques. Indeed, a critical point in indicate cancer in disparate portions of the percutaneously via a perineal approach), assessing the potential efficacy of focal gland [13]. However, the false-negative rate inducing intracellular ice formation and therapy is the determination of the clinical for prostate biopsy is substantial and may be microvascular damage, and eventually significance (e.g. biological aggressiveness) as high as 50% [14]. The traditional sextant leading to tissue ischaemia and necrosis. A of synchronous multifocal tumours. Hall prostate biopsy is unlikely to identify satellite significant advantage of cryosurgery is the et al. [6] reported that pathological lesions in multifocal prostate cancer. ability to visualize the ice ball in real time evaluation of the index tumour accurately Unfortunately, the sampling error associated using ultrasonography, allowing the surgeon predicted the clinical behaviour of the entire with prostate biopsy is not fully corrected to assess the adequacy of the ‘kill’ zone as gland, regardless of synchronous tumours in even with the use of extended biopsy well as to minimize injury to adjacent >90% of patients, suggesting that secondary schemes. Additional sampling of the lateral structures (e.g. the rectum or external urinary tumours in the majority of contemporary and apical peripheral zone increases accuracy, sphincter). patients may indeed be clinically [15] but still misses many tumours with insignificant. Furthermore, it has been extended 10–12 core biopsy schemes [13]. High-intensity focused ultrasound uses demonstrated that 80% of secondary Using office-based saturation biopsy, Walz intersecting, precision-focused ultrasound tumours are <0.5 mL, a common criterion for et al. [16] identified cancer in 41% of 161 waves to induce hyperthermia (up to 90 °C) the determination of clinical insignificance. patients who had previously undergone

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