前列腺癌出现骨转移的治疗方案 – Treatment options for bone metastases in prostate cancer

（前言）
前列腺癌是一种男性癌症，也是新加坡男性的第三大常见癌症，占2008年至2018年所有男性癌症病例的12%。在过去几十年里，其发病率不断上升。
前列腺癌主要发生在老年男性身上，尤其是在50岁以上人群中显著增加。

问：
我67岁，被诊断患有前列腺癌，癌症已经扩散至骨骼。请问我有什么治疗方法可以选择？

答：
对于前列腺癌，医学界采用系统性抗癌治疗，包括：使用抗雄激素药物（anti-androgen agents）的内分泌疗法，或是动手术以降低睾酮水平，并防止癌细胞激素刺激；这些疗法将有助于减轻疼痛等症状，并从一开始就控制癌症状况。
前列腺癌若受到良好控制可以维持数年；病情受控制的时间长短取决于几个肿瘤的因素，其中包括肿瘤的分级（格里森分级系统Gleason score，是一种前列腺癌细胞侵略性的目测等级）。一般来说，格里森分级越高（大于7级），癌细胞越具有侵袭性，越难控制病变速度。

阻断雄激素产生的途径

一旦癌症对内分泌治疗产生耐药性，下一个治疗方向可能就要使用药物来阻断雄激素产生，这些药物包括：阿比特龙（abiraterone ）、泼尼松（　prednisolone）、恩扎鲁胺（enzalutamide）、镭-223（Radium-223）和化疗药物例如：多西紫杉醇（docetaxel）、卡巴他赛（cabazitaxel）和米托蒽醌（mitoxantrone）。这些药物的使用顺序需要医生临床判断，并依个人情况而异。

手术有助修复脊柱塌陷

如果上述系统性治疗无法控制癌症，那么就应该考虑对特别疼痛的骨转移部位进行局部外照射治疗（focal ultrasound waves therapy）。专科治疗中心采用局部超声波，治疗疼痛性骨转移。有的时侯，也需要手术来缓解脊椎转移（vertebral metastases）引起的脊髓压迫，并稳定脊柱。为了缓解疼痛，或需进行椎体成形术（vertebroplasty）或后凸成形术（kyphoplasty），这两项手术能够修复受到转移性疾病影响的骨折以及塌陷的椎体之高度。

可助预防骨折的药物

双膦酸盐（bisphosphonates）和地诺沙单抗（denosumab）这两种药物，已被证明可预防骨骼被侵袭的症状，如骨转移性激素抗性前列腺癌引起的骨折。地诺沙单抗在预防这类骨折事件方面，比双膦酸盐更有效，但其并发症概率也较高，包括：颌骨骨坏死（2.3%对1.3%）、低钙水平（13%对6%）。地诺沙单抗也可用来预防激素敏感型前列腺癌患者在接受抗雄激素治疗时的骨骼流失（bone loss）。
此外，对于那些钙质和维生素D水平较低的人，应补充钙质和维生素D。

问：
我感觉骨痛。医生说我现在骨骼很脆弱，容易骨折。有什么能帮助我减轻疼痛，提高骨骼强度，过着正常的生活？

答：
这种情况，医生会对症治疗。如果出现疼痛，阿片类镇痛药、非甾体抗炎药、破骨细胞抑制剂（如地诺沙单抗）和双膦酸盐，都可能帮助缓解疼痛。

(English version)

I am 67 year old and have been diagnosed with prostate cancer that has spread to my bone. What are my treatment options?

I also experience bone pain and my doctor says I am now prone to fractures because of my brittle bones. What can help reduce pain and improve bone strength so I can lead a normal life?

Symptomatic treatment – if there is pain, analgesia in the form of opioids, non-steroidal anti-inflammatory medications, osteoclast inhibitors such as denosumab, and bisphosphonates may be helpful in relieving the pain.

Systemic anti-cancer treatment in the form of hormonal therapy using anti-androgen agents or surgical means to reduce testosterone levels and prevent further cancer cells hormonal stimulation will be helpful in reducing symptoms such as pain and control cancer condition in the beginning. Good control of prostate cancer may be maintained for years; the duration of control depends on several tumour factors including what grade (Gleason score) of tumour it is, the higher the grade (> Gleason 7), the more aggressive it is with reduced progression free survival.

Once the cancer becomes hormone therapy resistant, the next line of treatment may involve the use of drugs to reduce alternative ways of androgen production such as abiraterone/prednisolone, enzalutamide, Radium-223, and chemotherapy agents – docetaxel, cabazitaxel, and mitoxantrone. The sequence of use of these agents require clinical judgement and differs from case to case.

Focal external beam therapy to a particularly painful bony metastatic site should be considered if above systemic treatment fails to control disease anymore. Focal ultrasound waves therapy may be available in specialty centres to treat painful bony metastases. Occasionally surgery may be needed to relieve spinal cord compression from vertebral metastases and stabilise the spine. Vertebroplasty or kyphoplasty involving restoration of the height of the fractured and collapsed vertebral bodies affected by metastatic disease may be needed for pain relief.

Both bisphosphonates (zoledronic acid) and denosumab have been proven to prevent skeletal related events such as fractures in bony metastases in hormone therapy resistant prostate cancer. Denosumab is more effective in preventing these events than zoledronic acid but has slightly higher complication of osteonecrosis of the jaw (2.3 versus 1.3%) and low calcium levels (13 versus 6%). Denosumab may also be used to prevent bone loss in patients with hormone sensitive prostate cancer while on anti-androgen therapy.

Calcium and vitamin D supplements should be given to those with low baseline levels of calcium and vitamin D.