Context: Focal targeted therapy of early stage prostate cancer (PCa) can ideally facilitate
the concept of personalized medicine in contemporary surgical oncology.
Objective: To present indications and outcomes of subtotal glandular ablation. This
treatment approach aims at the elimination of the cancer with preservation of
uninvolved tissue in an attempt to maintain a patient’s quality of life (QoL), including
undisturbed erectile function as well as urinary and bowel control.
Evidence acquisition: In 2002, the idea of a ‘‘lumpectomy’’ using an organ-sparing
approach for very localized PCa was proposed in parallel with organ-sparing breast
cancer treatment in women. Since then, a few pilot clinical studies have demonstrated
an acceptable short-term cancer control while minimizing the complication
rate. At the same time, progress in PCa screening has led to a significant stage and
tumor volumemigration toward early stage disease. In the past fewyears, a collection
of accumulated data has created a scientific background for further development of
this concept toward a wider implementation into clinical practice. In this paper, we
review all available literature from PubMed of the past 15 yr—from 1994 to 2008—
including the terms localized prostate cancer, focal therapy, organ preservation, and
morbidity.
Evidence synthesis: Several factors were identified that need to be taken into account to
further develop an organ-sparing treatment approach for early stage localized PCa and
turn this concept into clinical practice. First, novel thermoablative techniques such as
third-generation cryosurgery, high-intensity focused ultrasound (HIFU), vascular
photodynamic therapy and, electroporation can precisely target a tumor lesion within
the prostate while maintaining the integrity of the surrounding tissues. Second, new
ultrasound, magnetic resonance imaging (MRI) and molecular imaging techniques
may provide new means to detect small PCa lesions. Third, extended image-guided
biopsy protocols using a transperineal rather than a transrectal approach can provide a
more exact spatial distribution of PCa lesions within the prostate. Fourth, careful
patient selection using an individualized approach is a prerequisite for optimal preoperative
planning and a successful treatment outcome.
Conclusions: For patients with early stage localized PCa limited to one focus or lobe and
who express a great desire not to jeopardize their QoL, targeted focal therapy will likely
play a more significant role in the future as a tangible treatment option. Moreover,
focal therapy may fill the gap between active surveillance for low-risk PCa and radical
treatment for higher-risk forms.
The face of prostate cancer has been dramatically changed since the late 1980s when PSA was
introduced as a clinical screening tool. More men are diagnosed with small foci of cancers instead
of the advanced disease evident prior to PSA screening. Treatment options for these smaller
tumors consist of expectant management, radiation therapy (brachytherapy and external beam
radiotherapy) and surgery (cryosurgical ablation and radical prostatectomy). In the highly select
patient, cancer specific survival employing any of these treatment options is excellent, however
morbidity from these interventions are significant. Thus, the idea of treating only the cancer within
the prostate and sparing the non-cancerous tissue in the prostate is quite appealing, yet
controversial. Moving forward if we are to embrace the focal treatment of prostate cancer we
must: be able to accurately identify index lesions within the prostate, image cancers within the
prostate and methodically study the litany of focal therapeutic options available.
BACKGROUND: The application of focal therapy for low-risk prostate cancer (PCa) depended on appropriatepatient selection. No definitive criteria existed to characterize patients who may potentially benefitfrom an organ-sparing approach.We evaluated pretreatment clinical parameters that may predict unilateralPCa amenable to hemigland thermoablation.
METHODS: In total, 538 patients with complete data from the
Duke Prostate Center (DPC) Outcomes database with low- to low-intermediate–risk PCa (prostate-specificantigen <10 ng/mL, biopsy Gleason score 7, and clinical stage T1c-T2b) treated with radical prostatectomy(RP) were included in the dataset. Patients underwent diagnostic prostate biopsy (PBx) at Duke orcommunity hospitals from 1996 to 2006. Clinical and biopsy parameters were assessed as to the ability to
predict PCa unilaterality verified by RP pathology.
RESULTS: The strongest predictor of pathologic unilaterality
was PBx unilaterality. The sensitivity and specificity for biopsy unilaterality to predict pathologic unilateralitywas 88.4% and 34%, with a positive predictive value of 28% and a negative predictive value of 91%.PBx unilaterality (odds ratio [OR] ¼ 3.88; 95% confidence interval [CI], 2.14-7.05; P < .0005) and negativefamily history of PCa (OR ¼ 1.83; 95% CI, 1.09-3.05; P ¼ .21) was associated with a higher probability of unilateraldisease by multivariate regression.
CONCLUSIONS: Two pretreatment clinical variables were significantly
predictive of unilateral PCa: negative family history of PCa and PBx unilaterality. These variables maybe used to select men with low- to low-moderate–risk PCa for hemiablation. Further work is necessary todecrease the false-negative and false-positive rates associated with PBx to improve predictability for PCa laterality.
高密度焦点式超音波療法(high intensity focused ultrasound，
以下， HIFU)は， 強力な超音波エネルギー
を生体内の焦点領域に収束させ， 熱効果および， cav卜
tationと呼ばれる物理的効果により， 標的組織を熱i疑
問および組織破壊し， 治療効果を得るものである1)
前立腺癌に対するHIFUは， これまでに， 世界中で
30，000症例以トーに対して施行されており円治療機器と
してSonablate I! (SonaCar e Medical， Indianapolis，
USA) 3)および， Ablatherm"" (EDAP TMS， Vaulx-enVelin.
France)引の2機種が使用されてきた(本邦では，
Sonablate""が使用されている).
要旨近年， 前立腺癌のうち， 臨床的に予後に影響するとされる癌病巣の局在診断が可能であると考えられるように
なったことで， 局所治療が注目されている. 局所治療は，根治的治療とActive Surveillanceの中間に位置する治療概
念であり， 患者の予後に影響すると考えられる癌病巣を治療する一方， 正常組織を可能な限り温存し癌治療と患者
の機能温存を両立することを目的とするものである. このため， 局所治療が限局性前立腺癌の選択肢に加わること
で， それぞれの患者に対して， 従来よりも個別化された治療戦略を立てることが可能になると思われる. しかし， 今
後解決すべき課題もあり， 実施にあたっては， 患者の理解を十分に得ることは当然のこと， 厳格な患者選択， 正確な
癌局在診断に基づいた治療計画， 安全で正確な治療方法，そして効果判定方法を示した上で， 治療は行われることが重要である. また， 今後， 局所治療を限局性前立腺癌に対する治療選択肢のーっとするためには， 多くの症例の長期成績を集積する必要がある.
要旨 局所療法は，根治的治療とActive Surveillanceの中間に位置する治療概念と考えられ，患者の予後に影響する
と考えられる癌病巣を治療する一方，正常組織を可能な限り温存し，癌治療と患者の機能温存を両立することを目的
とするものである．高密度焦点式超音波療法（high intensity focused ultrasound，以下HIFU）は，治療領域を自
由な形に設定できること，数ミリ単位で治療領域，非治療 領域の組織変化の違いを鮮明にして治療することができる
ことから，前立腺癌に対する局所療法に適した治療法として期待される．しかし，これまでに報告された局所療法の
臨床成績は，その目的の一つである機能温存については，有用性が示されている一方，治療効果判定方法が施設間で異なり，経過観察期間も短期間である研究が多いため，その治療効果の有用性については，明らかではない．現在，
われわれは，HIFUを用いた局所療法のプロトコールを作成するため，“前立腺癌の局在診断”，“正確な治療の実
施”，そして“治療効果判定および再発評価”の方法について，基礎的，臨床的研究を行っている．今後，国際的な
コンセンサスや，これらの研究結果を考慮して作成されたプロトコールのもとで治療が行われ，さらに多施設共同研
究，他治療とのランダム化比較試験により，HIFUを用いた局所療法の有効性について，評価が行われることが望ま
れる．
