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Pros and cons of adjuvant chemo after radical cystectomy debated

Naomi Rodrig
10 Aug 2017
Dr Ken-Siang Png (left), Dr Cheng-Kuang Yang (right)
Optimizing perioperative chemotherapy in bladder cancer (BC) presents a clinical challenge, as reflected in a debate at the 15th Urological Association of Asia Congress held in Hong Kong, which focused on the benefits and drawbacks of adjuvant chemotherapy (AC) after radical cystectomy (RC).

International guidelines recommend cisplatin-based neoadjuvant chemotherapy (NAC) before RC, which has demonstrated a 5–10 percent improvement in 5-year overall survival (OS). [N Engl J Med 2003;349:859-866; J Clin Oncol 2011;29:2171-2177; Eur Urol 2005;48:202-205] However, the evidence is inconclusive in the adjuvant setting.

“Unfortunately, NAC remains largely underutilized,” said Dr Ken-Siang Png from the Tan Tock Seng Hospital in Singapore, who argued in favour of AC. “For those who did not receive NAC, there is a significant OS benefit in selected patients who received AC after RC.”

A number of randomized trials and meta-analyses of muscle-invasive BC (MIBC) data have demonstrated OS benefits with AC, although the majority failed to reach statistical significance. [J Clin Oncol 2010;28(suppl):abstract LBA4518; Ann Oncol 2012;23:695-700; Eur Urol 2014;66:42-54] One meta-analysis indicated that cisplatin-based combinations were more effective in this setting than cisplatin monotherapy, and provided a stronger benefit among patients with pN+ disease. [Eur Urol 2014;66:42-54]

The phase III European Organisation for Research and Treatment of Cancer (EORTC) 30994 study found a 22 percent improvement in OS with adjuvant cisplatin-based chemotherapy, but failed to reach statistical significance.  Immediate treatment significantly prolonged progression-free survival (PFS) vs deferred treatment (hazard ratio [HR], 0.54; p<0.0001), with 5-year PFS rates of 47.6 vs 31.8 percent. However, no significant improvement in OS was noted with immediate vs deferred treatment (HR, 0.78; p=0.13). The study, which included pT3/4 or pN1-3 non-metastatic (M0) patients who underwent RC, had limited power, having accrued only 284 out of 1,344 patients as planned. [Lancet Oncol 2015;16:76-86]

“Nevertheless, the study investigators suggest that immediate AC might benefit some subgroups of patients,” said Png. “Consequently, the European Association of Urology and the US Cancer Network now recommend adjuvant cisplatin-based combination therapy to patients with pT3/4 and/or pN+ disease who did not receive NAC.”

Dr Cheng-Kuang Yang from the Taichung General Hospital in Taiwan presented an opposing view, arguing that post-RC morbidity may delay the initiation of AC. “After RC, pathology upstaging from clinical and imaging tumour staging is common, as there is a high false negative rate for lymph nodes [LN]. Hence, guidelines suggest NAC due to the high possibility of LN metastases in MIBC,” he said.

Furthermore, studies indicate that MIBC patients are more likely to receive and complete NAC than AC. [Indian J Urol 2012;28:424-426]

“Current evidence with regard to OS, feasibility and safety supports the use of NAC when possible. Despite indications of a favourable effect of cisplatin-based AC, trials have failed to produce conclusive evidence as yet,” he claimed. “In the future, we need to find methods to identify individuals who are more likely to benefit from NAC and AC and those who should receive upfront RC.” 

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