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EAU 2018

EAU 2018: Who Benefits from Neoadjuvant Chemotherapy and Who Needs Immediate Radical Treatment?

Copenhagen, Denmark (UroToday.com) Dr. Peter Black from Vancouver, Canada discussed neoadjuvant chemotherapy versus those who need immediate treatment. Dr. Black started by stating that we have level 1 evidence supporting the use of neoadjuvant chemotherapy for MIBC [1], in addition to several large retrospective studies and meta-analyses. Furthermore, EAU guidelines tell us that neoadjuvant cisplatin-containing combination chemotherapy improves overall survival (OS) by 5-8% at 5 years. Additionally, the NICE guidelines in the UK state that we should offer neoadjuvant chemotherapy using a cisplatin combination regimen before radical cystectomy or radical radiotherapy to people with newly diagnosed MIBC for whom cisplatin-based chemotherapy is suitable. Finally, the AUA/ASCO/ASTRO/SUO guidelines suggest utilizing a multidisciplinary approach and clinicians should offer cisplatin-based neoadjuvant chemotherapy to eligible radical cystectomy patients prior to cystectomy. 

Indications for no neoadjuvant chemotherapy include:

  • WHO or ECOG PS of 2 or Karnofsky PS of 60-70%
  • Creatinine clearance (calculated or measured) < 60 ml/min
  • CTCAE v4 grade ≥2 audiometric hearing loss
  • CTCAE v4 grade ≥2 peripheral neuropathy
  • NYHA class III heart failure
Dr. Black subsequently made two important points that even though each of these above criteria is more likely in the elderly, age is not one of the criteria. Secondly, there should be consideration for cisplatin-based neoadjuvant chemotherapy in patients with eGFR as low as 40 ml/min. Dr. Black cautions however, that we should not compromise with the use of carboplatin. Instead, we should head directly to cystectomy, which is supported by the AUA guidelines. 

Patients that are cN+ should all be treated with upfront chemotherapy. Dr. Black notes that this is induction chemotherapy and not neoadjuvant chemotherapy and should be for 4 and sometimes 6 cycles. Surgery may play a role in this setting in two cases (i) consolidative surgery (or radiotherapy) if there is an appropriate response, and (ii) if platinum-ineligible, consider surgery if there is lower volume nodal disease, since not all of these patients are pN+. The MD Anderson Cancer Center clinical risk stratification has been used and validated in a USC cohort:

ClinicalRiskStratification

Variant histology includes most commonly micropapillary, sarcomatoid and plasmacytoid. These entities have a high risk of micrometastasis and upstaging, however there is uncertainty whether chemotherapy is effective. Dr. Black considers it reasonable to proceed with cystectomy without neoadjuvant chemotherapy if the patient is cT2-cTaN0M0 with variant histology. With regards to molecular markers to predict response to neoadjuvant chemotherapy, the EAU guidelines state that currently there are no tools available to select patients who have a higher probability of benefiting from neoadjuvant chemotherapy. 

Dr. Black concluded with several take-home messages: (i) cisplatin-ineligible patients should not receive neoadjuvant chemotherapy, (ii) otherwise cisplatin-based neoadjuvant chemotherapy is default for all non-metastatic MIBC, (iii) clinical risk stratification is imperfect, but neoadjuvant chemotherapy is less important in lowest risk patients, and (iv) molecular markers will soon guide the use of neoadjuvant chemotherapy.


References:

1. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003;349(9):859-866.

Presented by: Peter C. Black, Vancouver Prostate Centre, Vancouver, BC, Canada

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, twitter: @zklaassen_md at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark