SIU 2017: Neoadjuvant Chemo - When, What and Why?

Lisbon, Portugal (UroToday.com) Dr. Konety focused his talk on the current status of neoadjuvant chemotherapy for the treatment of MIBC. He focused on the when, what and why?

Why Neoadjuvant or Perioperative chemotherapy?

There were 5 clinical trials that assessed the role of NAC prior to cystectomy, of which only two had significant benefit demonstrated favoring NAC

o The EORTC was the only with significant two-tailed p-value; at 8-year time frame mark, demonstrated 16% HR reduction (p=0.03)
o The SWOG study did not demonstrate a two-tailed p-value

ABC Meta-analysis demonstrated clear benefit to NAC with cisplatin based chemotherapy

o HR 0.89, p=0.02 – NNT was 20
o But, comes with toxicity with it (and even very small mortality in EORTC trial)

As a result, almost all the guidelines consider this Level 1 Evidence and recommend NAC to eligible patients prior to radical cystectomy

o Must be cisplatin based chemotherapy – do not offer it if not cisplatin based!
o Consolidation with RC is critical

Patients with complete response (pT0) do very well

o But patients with any response (pTa, pTIS, pT1) still do better than those with no response
o Even patients with stable pT2 disease do better than those who progress

NAC utilization is increasing worldwide – up to 41% in the United States

o Adjuvant chemo is stable ~21%

What is the best chemotherapy regimen?

NAC appears to be better than adjuvant – many patients after RC are no longer eligible for chemotherapy, so the window is lost for effective systemic therapy
ddMVAC (dose dense MVAC) is better than MVAC and Gem-Cis – as its shorter duration, similar response rates, better tolerated. Needs GM-CSF support.

o   Gem-Cis is non-inferior to MVAC
o   ddMVAC has pT0 rates ~30%
o   90% of patients complete the regimen – which is very important

If Cisplatin cannot be given, then no chemotherapy is better than carboplatin!

o Response rates are so low, that risks outweigh benefit

Who is not fit for chemotherapy?

Current ineligibility criteria for clinical trials: (consensus opinion by medical oncologists)

o   Poor performance status – ECOG 2 or KPS of 60-70%
o   Creatinine Clearance < 60 mL/min
o   >= Grade 2 hearing loss
o   >= Grade peripheral neuropathy
o   NYHA Class III heart failure

What about adjuvant chemo?

o   Any patient that went to RC without NAC
o   pT3/4 disease
o   pN+ disease

Common risk factors for node-positive disease? 30% if they have the following risk factors?

o   Hydronephrosis
o   LVI
o   Variant histology
o   Prior intravesicle therapy
o   cT3 disease

Many Urologists have begun to consider risk stratification for receipt of NAC based on the risk of having node positive disease. However, there is not yet good enough evidence that we can discriminate based on clinical factors alone.

Other predictors of chemotherapy response:

Genotypic markers of response – ie basal type molecular
p53-like luminal cells – not associated with chemotherapy response
Test for ERCC mutation – may be chemo resistant
ERBB2 – high expression associated with good response

What happens if NAC does not work? Persistent disease or even progression?

Mayo clinic – patients who NAC without response had worse response (RFS) to patients who just had RC without NAC!

o Similar findings for Minnesota group

Perhaps NAC is good for those who respond – but not good for those who don’t response
Risk stratification is going to be important! Particularly with genomic markers

Presented by: Badrinath Konety

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal

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