Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer

  • Review
  • Intervention




Hormone therapy for early prostate cancer has demonstrated an improvement in clinical and pathological variables, but not always an improvement in overall survival. We performed a systematic review of both adjuvant and neo-adjuvant hormone therapy combined with surgery or radiotherapy in localised or locally advanced prostate cancer.


The objective of this review was to undertake a systematic review and, if possible, a meta-analysis of neo-adjuvant and adjuvant hormone therapy in localised or locally advanced prostate cancer.

Search methods

We searched MEDLINE (1966 to 2006), EMBASE, The Cochrane Library, Science Citation Index, LILACS, and SIGLE for relevant randomised trials. Handsearching of appropriate publications was also undertaken.

Selection criteria

Randomised or quasi-randomised controlled trials of patients with localised or locally advanced prostate cancer, that is, stages T1 to T4, any N, M0, comparing neo-adjuvant or adjuvant hormonal deprivation in combination with primary therapy (radical radiotherapy or radical prostatectomy) versus primary therapy alone were included in this review.

Data collection and analysis

Data were extracted from eligible studies and assessed for quality, and included information on study design, participants, interventions, and outcomes. Comparable data were pooled together for meta-analysis with intention-to treat principle.

Main results

Men with prostate cancer have different clinical outcomes based on their risk (T1 to T2, T3 to T4, PSA levels and Gleason score). However, the majority of studies included in this review did not report results by risk groups; therefore, it was not possible to perform sub-group analysis.

Neo-adjuvant hormonal therapy prior to prostatectomy did not improve overall survival (OR 1.11, 95% CI 0.67 to 1.85, P = 0.69). However, there was a significant reduction in the positive surgical margin rate (OR 0.34, 95% CI 0.27 to 0.42, P < 0.00001) and a significant improvement in other pathological variables such as lymph node involvement, pathological staging and organ confined rates. There was a borderline significant reduction of disease recurrence rates (OR 0.74, 95% CI 0.55 to 1.0, P = 0.05), in favour of treatment. The use of longer duration of neo-adjuvant hormones, that is either 6 or 8 months prior to prostatectomy, was associated with a significant reduction in positive surgical margins (OR 0.56, 95% CI 0.39 to 0.80, P = 0.002).

In one study, neo-adjuvant hormones prior to radiotherapy significantly improved overall survival for Gleason 2 to 6 patients; although, in two studies, there was no improvement in disease-specific survival (OR 0.99, 95% CI 0.75 to 1.32, P = 0.97). However, there was a significant improvement in both clinical disease-free survival (OR 1.86, 95% CI 1.93 to 2.40, P < 0.00001) and biochemical disease-free survival (OR 1.93, 95% CI 1.45 to 2.56, P < 0.00001).

Adjuvant androgen deprivation following prostatectomy did not significantly improve overall survival at 5 years (OR 1.50, 95% CI 0.79 to 2.85, P = 0.2); although one study reported a significant disease-specific survival advantage with adjuvant therapy (P = 0.001). In addition, there was a significant improvement in disease-free survival at both 5 years (OR 3.73, 95%CI 2.30 to 6.03, P < 0.00001) and 10 years (OR 2.06, 95% CI 1.34 to 3.15, P = 0.0009).

Adjuvant therapy following radiotherapy resulted in a significant overall survival gain apparent at 5 (OR 1.46, 95% CI 1.17 to 1.83, P = 0.0009) and 10 years (OR 1.44, 95% CI 1.13 to 1.84, P = 0.003); although there was significant heterogeneity (P = 0.09 and P = 0.07, respectively). There was also a significant improvement in disease-specific survival (OR 2.10, 95% CI 1.53 to 2.88, P = 0.00001) and disease-free survival (OR 2.53, 95% CI 2.05 to 3.12, P < 0.00001) at 5 years.

Authors' conclusions

Hormone therapy combined with either prostatectomy or radiotherapy is associated with significant clinical benefits in patients with local or locally advanced prostate cancer. Significant local control may be achieved when given prior to prostatectomy or radiotherapy, which may improve patient's quality of life. When given adjuvant to these primary therapies, hormone therapy, not only provides a method for local control, but there is also evidence for a significant survival advantage. However, hormone therapy is associated with significant side effects, such as hot flushes and gynaecomastia, as well as cost implications. The decision to use hormone therapy should, therefore, be taken at a local level, between the patient, clinician and policy maker, taking into account the clinical benefits, toxicity and cost. More research is needed to guide the choice, the duration, and the schedule of hormonal deprivation therapy, and the impact of long-term hormone therapy with regard to toxicity and the patient's quality of life.








我們在MEDLINE (1966至2006年)、EMBASE、The Cochrane Library、Science Citation Index、LILACS和SIGLE等資料庫搜尋隨機試驗,也個別搜尋合適的文獻。


這篇回顧分析所收錄的隨機或半隨機對照試驗,主要是衡量局部及局部侵犯性前列腺癌 (期別T1T4,任何N及M0),運用新輔助和輔助性荷爾蒙治療,合併主要治療 (根除性前列腺切除術或放射治療),與未合併荷爾蒙治療做比較。


我們對於所擷取的資料進行品質評估,其中包含了試驗的設計、受試者、治療及預後的資訊。以治療意向 (intentiontotreat) 將相對應的同類資料合併,以做統合分析(metaanalysis)。


前列腺癌患者根據不同的風險 (T1  T2,T3  T4,前列腺特異抗原高低,及Gleason 分數),有不同的臨床預後。然而,大部分收錄在本文的各項研究,並不是根據病患的風險來報告臨床結果,所以無法根據不同風險來做分析。前列腺根除手術前之新輔助荷爾蒙治療,無法延長整體存活 (OR 1.11,95% CI 0.67 至 1.85,P = 0.69),但是卻顯著地減少了前列腺根除手術後標本的切緣陽性率 (OR 0.34,95% CI 0.27 至 0.42,P < 0.00001),並對其他病理結果如淋巴節侵犯、病理分期和器官局限率 (organconfined rates) 皆有改善的作用。而對於疾病復發率的降低,僅達邊緣性顯著 (borderline significant) 的效果 (OR 0.74,95% CI 0.55 至 1.0,P = 0.05)。手術前更長期的使用新輔助性荷爾蒙治療 (手術前給予6或8個月),可有效地減少邊緣陽性率 (OR 0.56,95% CI 0.39 至 0.80,P = 0.002)。 在某一研究中,放射治療前接受新輔助性治療,可以改善Gleason 2至6分病人之整體存活率。但是在另外2個研究,接受長期新輔助性荷爾蒙治療病患之疾病相關存活率,無明顯的改進 (OR 0.99,95% CI 0.75 至 1.32,P = 0.97),然而,病患之臨床無病存活 (OR 1.86,95% CI 1.93 至 2.40,P < 0.00001) 和PSA無復發存活 (OR 1.93,95% CI 1.45 至 2.56,P < 0.00001) 則有顯著的改善。根除性前列腺切除後之輔助性荷爾蒙治療,無法改善5年整體存活率 (OR 1.50,95% CI 0.79 至 2.85,P = 0.2);但是有一研究報告輔助性荷爾蒙治療,顯著地延長疾病相關存活 (P = 0.001)。除此之外,輔助性荷爾蒙治療對於手術後病患之5年 (OR 3.73,95%CI 2.30 至 6.03,P < 0.00001) 及10年 (OR 2.06,95% CI 1.34 至 3.15,P = 0.0009) 之無病存活率,有明顯地改善。放射治療後之輔助性荷爾蒙治療能有意義地改善病患之5年 (OR 1.46,95% CI 1.17 至 1.83,P = 0.0009) 及10年整體存活率 (OR 1.44,95% CI 1.13 至 1.84,P = 0.003),然而以上研究有顯著的差異性 (P = 0.09 and P = 0.07,respectively)。輔助性荷爾蒙治療同時對於5年疾病相關存活率 (OR 2.10,95% CI 1.53 至 2.88,P = 0.00001) 及無病存活率 (OR 2.53,95% CI 2.05 至 3.12,P < 0.00001) 皆達有效的改善。





此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。


早期前列腺癌的治療在腫瘤醫學領域是最具爭議性的,因為其初步治療包括了手術治療、放射治療、荷爾蒙治療 (藥物或外科去勢�睪丸切除) 及密切追蹤法。治療計畫之進行,須取決於病患及醫師考量治療之風險、益處及疾病進程來決定。因為前列腺癌與男性荷爾蒙有關,因此使用荷爾蒙藥物來降低血液循環中的男性荷爾蒙,是治療各種期別前列腺癌的好方法。最近越來越多有關於荷爾蒙合併手術及放射治療的研究被發表。本篇系統性回顧,主要在探討荷爾蒙合併手術及放射治療,在局部及局部侵犯性前列腺癌所扮演的角色。 本篇回顧分析之結果表示,在主要治癒療法 (前列腺根除術) 前給予3至6個月之新輔助荷爾蒙治療,並不會顯著地改善整體或疾病相關存活。但是若在放射治療前進行荷爾蒙治療,則可明顯地改善無病存活 (將近90%)。根除性前列腺切除術之前給予新輔助荷爾蒙治療,可有效地改進與預後不佳有關之病理結果,如邊緣陽性率和淋巴結陽性的比例。與單純接受手術治療比較,手術治療後合併輔助性荷爾蒙治療,無法改變整體及疾病相關存活。然而,放射治療後之輔助性荷爾蒙治療,卻可改善病患之10年整體、疾病相關及無病存活。但是荷爾蒙治療本身也存在著許多副作用,如臉潮紅及男性女乳症。是否使用荷爾蒙治療必須由病患和醫師來共同討論,同時考量到治療的益處及副作用,再做出決定。








MEDL1NE(1966年~2006年)、EMBASE、コクラン・ライブラリ、Science Citation Index、LILACSおよびSIGLEから関連したランダム化試験を検索した。適切な出版物のハンドサーチも行った。






前立腺癌男性は、そのリスク(T1~T2、T3~T4、PSAレベルおよびGleasonスコア)に基づいて臨床アウトカムが異なる。しかしながら、本レビューに含めた研究のほとんどはリスクグループ別の結果を報告していないので、サブグループ解析を行うことはできなかった。前立腺切除術前の術前補助ホルモン療法は、全生存率を改善しなかった(OR 1.11、95%CI 0.67~1.85、P=0.69)。しかしながら、手術切除断端の陽性率に有意な低下がみられ(OR 0.34、95%CI 0.27~0.42、P<0.00001)、リンパ節転移、病理学的ステージ分類、臓器限局性の割合などのその他の病理学的変数に有意な改善があった。疾患再発率に、治療を支持するボーダーラインの有意な低下があった(OR 0.74、95%CI 0.55~1.0、P=0.05)。術前補助ホルモンの使用が長いと、すなわち前立腺切除術前に6ヶ月または8ヶ月使用すると、手術切除断端の陽性率が有意に減少した(OR 0.56、95%CI 0.39~0.80、P=0.002)。1件の研究で、放射線療法前の術前補助ホルモン療法はGleasonスコア2~6の患者の全生存率を有意に改善したが、2件の研究では疾患特異的生存率に改善はみられなかった(OR 0.99、95%CI 0.75~1.32、P=0.97)。しかしながら、臨床的無病生存率に有意な改善があり(OR 1.86、95%CI 1.93~2.40、P<0.00001)、生化学的無病生存率にも有意な改善があった(OR 1.93、95%CI 1.45~2.56、P<0.00001)。前立腺切除術後の補助アンドロゲン除去療法は5年目の全生存率を有意に改善しなかったが(OR1.50、95%CI0.79~2.85、P=0.2)、1件の研究は補助療法による疾患特異的生存率の有意な利益を報告していた(P=0.001)。さらに、5年目の無病生存率に有意な改善がみられ(OR 3.73、95%CI 2.30~6.03、P<0.00001)、また10年目の無病生存率にも有意な改善があった(OR 2.06、95%CI 1.34~3.15、P=0.0009)。放射線療法後の補助療法の結果、有意な全生存率の利益が5年目に明らかで(OR 1.46、95%CI 1.17~1.83、P=0.0009)、10年目にも明らかであったが(OR 1.44、95%CI 1.13~1.84、P=0.003)、有意な異質性があった(それぞれP=0.09とP=0.07)。5年目の疾患特異的生存率にも有意な改善があり(OR 2.10、95%CI 1.53~2.88、P=0.00001)、無病生存率にも有意な改善があった(OR 2.53、95%CI 2.05~3.12、P<0.00001)。




監  訳: 2006.12.27

実施組織: 厚生労働省委託事業によりMindsが実施した。

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Plain language summary

Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer

The management of early prostate cancer is one of the most controversial areas in the field of cancer medicine with surgery, radiotherapy, primary hormonal therapy (achieved either by medication or by the surgical removal of the testes - orchidectomy) and watchful waiting, all being acceptable forms of initial treatment. Treatment decision making is often based on patient and provider preferences taking into account the risks and benefits of therapies and disease progression. Since prostate cancer is driven, in part by male sex hormones, the use of hormonal treatment to reduce the level of circulating male hormones is a potentially very useful method of treating all stages of this disease. Recently, research on the use of such hormonal therapy in combination with both surgery and radiotherapy has increased. This systematic review combines the results of all the important trials looking at the role of hormones in combination with surgery and radiotherapy for localised and locally advanced prostate cancer.

The results of this review indicate that neo-adjuvant hormone therapy administered three to six months before the primary curative therapy (radical prostatectomy radical radiotherapy) did not, as yet, result in a detectable improvement in overall survival or disease-specific survival. There was, however, a significant improvement in disease-free survival (approximately 90%) when given before radiotherapy. Neo-adjuvant hormone therapy prior to radical prostatectomy also significantly improved pathological variables associated with poor prognosis, such as the positive surgical margin rate and the proportion of patients with positive lymph nodes. Adjuvant hormone therapy following prostatectomy did not change overall or disease-specific survival compared to prostatectomy alone. However, adjuvant therapy following radiotherapy significantly improved overall survival and disease-specific survival up to 10 years post-treatment. Disease-free survival was also significantly improved at 10 years. Hormone therapy is associated with a number of side effects including hot flushes and gynaecomastia. The decision to use these agents has to be made after a full discussion between the patient and the physician regarding the disease risk of the patient, the benefits from the use of additional hormones and the side effects of hormonal therapy.