NSGCT stage I 非精原睾丸癌1期

6.3    NSGCT stage I 非精原睾丸癌1期
Up to 30% of NSGCT patients with clinical stage I (CS1) disease have subclinical metastases and will relapse if
surveillance alone is applied after orchidectomy.
如果在睾丸根除手术后只进行监视治疗，非精原睾丸癌临床1期的患者有高达30%的人群发生亚临床转移，随后复发。

6.3.1   Surveillance  监视治疗
Improvements in clinical staging and follow-up methods, and the availability of effective salvage treatment with
cisplatin-based chemotherapy and post-chemotherapy surgery, have led to studies of only close surveillance
after orchidectomy in CS1 NSGCT patients. The largest reports of the surveillance strategy indicate a
cumulative relapse rate of about 30%, with 80% of relapses occurring during the first 12 months of follow-up,
12% during the second year and 6% during the third year, decreasing to 1% during the fourth and fifth years,
and occasionally even later (122-126). About 35% of relapsing patients have normal levels of serum tumour
markers at relapse. About 60% of relapses are in the retroperitoneum. Despite very close follow-up, 11% of
relapsing patients presented with large-volume recurrent disease.
临床分期和后续方法的进步；拯救性治疗（以顺铂为基础的化疗）以及化疗后手术有效性的提高。这2方面因素引导人们针对睾丸根除手术后临床I期的病人，开展只进行监视治疗的研究。大多数监控策略报告表明，累积复发率大约为30％；其中：80%的复发发生在12月内，12%的复发发生在2年内，6%的复发发生在3年内，1%的复发发生在4-5年内，更长时间的复发也偶然发生。大约35%的复发病人在复发时瘤标指示正常。60%的复发发生在腹膜后。尽管进行了严密的监视，依然有11%的病人发生了大面积的经常性的复发。

The somewhat lower relapse rates reported from surveillance studies compared with some series of patients
staged by RPLND (127) can be explained by the fact that some patients (presumably at risk) are excluded once
surveillance is advised. Based on the overall cancer-specific survival data, surveillance within an experienced
surveillance programme may be offered to patients with non-risk stratified clinical stage I non-seminoma as
long as they are compliant and informed about the expected recurrence rate as well as the salvage treatment
(128,129).
有一些监控研究报告了，比采用清扫手术治疗的患者，还要低的复发率；可以解释为：这些研究排除了高复发风险的患者，只对低风险患者实施了监控。基于整体的癌症生存数据，监控治疗也可以用于不满足风险要求的患者，这就要求医生具有丰富的监控经验，并且保证病人积极配合，而且要通告病人预期的复发机率和拯救性治疗的方法。

6.3.2   Primary chemotherapy 基础化疗
Several studies involving two courses of chemotherapy with cisplatin, etoposide and bleomycin (PEB) as
primary treatment for high-risk patients (having about 50% risk of relapse) have been reported (130-135). In
these series, involving more than 200 patients, some with a median follow-up of nearly 8 years (130), a relapse
rate of only 2.7% was reported, with very little long-term toxicity. Two cycles of cisplatin-based adjuvant
chemotherapy do not seem to adversely affect fertility or sexual activity (136). However, the very-long term
(> 20 years) side effects of adjuvant chemotherapy in this setting are currently unknown, and this should be
taken in consideration for decision-making; especially the long-term cardio-vascular effects of chemotherapy in
GCT survivors (137).
有几个研究报告了研究成果，这些研究是以两个疗程的顺铂、依托泊苷和博莱霉素（PEB）作为基本化疗，针对高风险的患者（大约50%的复发率）的。这一系列的研究中，涉及到超过200名患者，其中部分患者进行了接近8年的中度随访跟踪，得到了复发率仅为2.7%，并且长期毒性很低的报告。两个疗程以顺铂为基础的化疗似乎对生育或性活动并没有产生不利影响。然而，这种化疗的长期（>20年）副作用现在依然不知道，在做决定时，需要考虑这一点，特别是要考虑化疗对心血管长期影响。

It is important to be aware of the slow-growing retroperitoneal teratomas after primary chemotherapy (138).
The results of cost analyses comparing surveillance, RPLND and primary chemotherapy show different
results among the reported studies, possibly because of differences in intensity and costs related to follow-up
procedures (139). With a low frequency of follow-up CTs (such as has been proven effective for the surveillance
strategy in non-seminoma CS1), the costs of follow-up can be considerably reduced (140).
化疗后腹膜后畸胎瘤缓慢的生长需要重点关注。在这些公开的研究中，监控、腹膜后淋巴清扫和基础化疗的成本分析的结果各不相同，可能是因为相关的后续治疗的强度和成本各不相同。后续CT检查（已经被证实对于非精原临床1期监控策略行之有效）频率越低，后续的成本也越低。

6.3.3   Risk-adapted treatment 风险适应的治疗
Risk-adapted treatment is based on the risk factor vascular invasion. Stratifying patients with CS1 NSGCT
according to their presumed risk of relapse is a rational option, as several studies have reported similar survival
rates and a final cure rate close to 100% with all available treatment options using the risk-stratifying approach
(130-135,141-144). Risk-adapted treatment is therefore an equally effective alternative treatment of choice in
CS1 NSGCT.
风险适应的治疗基于风险因素-血管侵犯。对临床1期的患者依照推算的风险进行分类对待是一个合理的选择，一些研究表明使用风险分类的方法采用适用的治疗选择可以获得100%的生存率和最终治愈率。因此，风险适应的治疗同样是一个有效的替代治疗选择。

If the risk-adapted policy is applied, patients with vascular invasion are recommended to undergo adjuvant
chemotherapy with two cycles of PEB, and patients without vascular invasion are recommended to undergo
surveillance. Only if patients or doctors are not willing to accept the consequent risk-adapted treatment,
or if there are circumstances that militate against the risk-adapted treatment option, should the remaining
treatments be considered.
如果采用风险适应的治疗，建议有血管入侵的病人进行2个疗程的PEB化疗，建议没有有血管入侵的病人进行监视治疗。只有当病人或者医生不愿意接受风险适应的治疗的后果，或者在不允许风险适应治疗的情形下，才可以考虑其它的治疗方法。

  Thus, the decision about treatment should be based on a thorough discussion with the patients,
taking into account the described advantages and disadvantages, as well as the individual situation of the
patient and/or the treatment centre. The Swedish-Norwegian Testicular Cancer Project (SWENOTECA) recently
showed that in a large population-based study with a risk-adapted approach within a management programme
and a median follow-up of 4.7 years, the relapse rate was 3.2% for patients with vascular invasion treated
with only one adjuvant PEB (145). Taken together, about 300 patients with high risk CS I have been adjuvantly
treated with 1 x PEB with a follow-up of more than 5 yrs. Still, a randomised trial between 1 and 2 courses of
PEB is accruing patients. As long as 1 x PEB has not been proven superior or at least equivalent to 2 courses
PEB, this adjuvant treatment cannot be recommended outside of a clinical trial or a prospective registry.
治疗方法的决定应该与病人深入讨论，考虑到治疗的优点和缺点，同时考虑到病人和医疗机构的个体情况差异。瑞典 - 挪威睾丸癌项目（SWENOTECA）最近公布了一项大量人数参与的风险适应治疗项目的研究结果，这项研究使用了一套管理程序，进行了4.7年的中度随访，对有血管入侵的病人只进行1个疗程的PEB化疗，得到复发率为3.2%的结果。概况来说，有300名临床1期的高风险病人接受了1个疗程的PEB化疗和5年的随访。然而，1个疗程和2个疗程的随机对比实验正在积累病人数量。只要1个疗程的化疗还没有被证明比2个疗程的更好或者效果相同，就不推荐这种不是临床实验和prospective registry的治疗方法。

6.3.4   Retroperitoneal lymph node dissection 腹膜后淋巴清扫
If RPLND is performed, about 30% of patients are found to have retroperitoneal lymph node metastases, which
corresponds to pathological stage II (PS2) disease (146-148). If no retroperitoneal metastases are found at
RPLND (PS1), approximately 10% of the PS1 patients relapse at distant sites (92,128,149-151).
如果进行了腹膜后淋巴清扫，大约有30%的病人被发现腹膜后淋巴有癌症转移，这时定义为病理II期 (PS2) 。如果没有发现腹膜后淋巴的癌症转移，定义为病理I期(PS1)，大约有10%的病理I期患者会在远端位置发生复发。

The main predictor of relapse in CS1 NSGCT managed by surveillance, for having PS2 disease and for relapse
in PS1 after RPLND, is histopathological evidence of vascular invasion by tumour cells in, or near, the primary
tumour in the testis (92,123,128,151,152). The presence of vascular invasion seems to be a very robust
parameter, and is clinically usable even without centralised review by an expert panel (142,151). Vascular
invasion was the most predictive of stage in a multifactorial analysis. The absence of vascular invasion has a
negative predictive value of 77%, thus allowing for surveillance in low-risk compliant patients (92).
对于腹膜后淋巴清扫手术后的病理II期和病理I期复发的监测环节中发现：是否复发的主要预测依据是血管侵入的病理现象，血管侵入是指睾丸肿瘤里面或者附近癌细胞是否侵入血管。血管侵入的存在是一个非常可靠的参数，即使没有专家团队会诊，也具有临床价值。在多因素分析阶段血管侵入最主要预测因素。没有血管侵入将有77%的阴性预测结果，因而对于这部分低风险患者可以采用监测治疗。

Patients without vascular invasion constitute about 50-70% of the CS1 population, and these patients have
only a 15-20% risk of relapse on surveillance, compared with a 50% relapse rate in patients with vascular
invasion. The risk of relapse for PS1 patients is less than 10% for those without vascular invasion and about
30% for those with vascular invasion (142,151,153,154).
临床1期的患者中有50%-70%没有血管侵入的现象，这些病人采用监测治疗只有15-20%的复发几率，而有血管侵入的患者将有50%的复发几率。没有血管侵入的病理1期患者复发率小于10%，有血管侵入的病理1期患者复发率大约为30%。

If CS1 patients with PS2 are followed up only after RPLND, about 30% relapse, mainly at sites outside the
abdomen and pelvis. The risk of relapse depends upon the amount of retroperitoneal disease resected (155-
157). If two (or more) courses of cisplatin-based chemotherapy are given adjuvant to RPLND in PS2 cases, the
relapse rate is reduced to less than 2%, including teratoma relapse (128,152,158). The risk of retroperitoneal
relapse after a properly performed nerve-sparing RPLND is very low (less than 2%), as is the risk of ejaculatory
disturbance or other significant side-effects (152,155,156).
临床1期（CS1）被确诊为病理2期的患者，如果只进行清扫手术，那么复发大概为30%，而且主要发生在腹部、盆腔以外。复发的风险依赖于腹膜后切除的病灶数量。如果给病理2期（PS2）的病人实施以顺铂为基础的2个（或更多）疗程的化疗，复发概率（包括畸胎瘤）将减少到2%。进行恰当的保留性神经的清扫手术，腹膜后复发的风险是非常低的（小于2%），同时射精干扰或其他重大副作用的风险也很小。

The follow-up after RPLND is much simpler and less costly than that carried out during post-orchidectomy
surveillance because of the reduced need for abdominal CT scans (152). If there is a rare indication to perform
a staging RPLND, a laparoscopic or robot-assisted RPLND is feasible in expert hands. This minimal-invasive
approach cannot be recommended as standard approach outside of a specialized laparoscopic centre (159-
162). In a randomised comparison of RPLND with one course of PEB chemotherapy, adjuvant chemotherapy
significantly increased the 2-year recurrence-free survival to 99.41% (confidence interval [CI] 95.87%, 99.92%)
as opposed to surgery, which had a 2-year recurrence-free survival of 92.37% (CI 87.21%, 95.50%). The
difference was 7.04%, CI 2.52%, 11.56%. The hazard ratio to experience a tumour recurrence with surgery as
opposed to chemotherapy was 7.937, CI 1.808, 34.48. Therefore, one course of adjuvant PEB is superior to
RPLND with regard to recurrence rates in patients unstratified for risk factors (163). In the SWENOTECA data
mentioned in section 7.3.3 it was also found that one adjuvant PEB reduced the number of recurrences to
3.2% of the high risk and to 1.4% of the low risk patients (145).
清扫手术的后续治疗比直接化疗的后续治疗会更简单、更低廉，因为不需要进行腹膜后CT检查了。由专家使用腹腔镜或机器人辅助的用于做病理分级的淋巴清扫微创手术是可行的，但是比较少见。所以除非在特定腹腔镜中心做手术，否则腹腔镜和机器人辅助不作为标准治疗方法。随机对比清扫手术与一个疗程的PEB化疗，辅助化疗可以显著的增加2年无瘤存活率，为99.41%；清扫手术的2年无瘤存活率，为92.37%；差异为7.04%。清扫手术对比辅助化疗的风险比是7.937。所以，考虑到复发风险，没有进行风险分类的患者（估计是指没有进行pN1-pN4的病理分级）应该优先选择一个疗程的辅助化疗，而不是清扫手术。瑞典 - 挪威睾丸癌项目提到（7.3.3节）一个疗程的辅助PEB化疗可以将高风险患者的复发率降低到3.2%，低风险患者的复发率降低到1.4%。


译者注：
recurrence-free survival： 无瘤存活率（!=100%-复发率）
hazard ratio：风险比（专业的概率词汇）
adjuvant chemotherapy ： 睾丸切除手术后的辅助化疗（参考 http://www.ncbi.nlm.nih.gov/pubmed/18458040可以联系上下文来确认这个含义）