18 juli 2020: Bron: The . 2020 Apr 18; 395(10232): 1268–1277.

Chemotherapie met een combinatie van gemcitabine met cisplatin of carboplatin die binnen 90 dagen na een nieroperatie - nefrodetectomie werd gestart, verbeterde de ziektevrije overleving op drie jaars meting met 25 procent in vergelijking met een wait-and-see programma bij patiënten met lokaal gevorderde UTUC - kanker van de bovenste urinewegen (Urotheel carcinoom). Kanker van de bovenste urinewegen is een vorm van kanker die overigens zelden voorkomt, gemiddeld bij 2 op de 100.000 mensen. Het is wel bijzonder dat na een nieroperatie er toch chemotherapie wordt gebruikt. Want voor nierkanker werkt chemotherapie niet. 

Uit het studierapport: 

Urotheliale carcinomen van de bovenste urinewegen (UTUC's) zijn zeldzaam, met een slechtere prognose voor elk stadium dan urotheelcarcinomen van de urineblaas. Er bestaat geen internationale consensus over het voordeel van adjuvante chemotherapie voor patiënten met UTUC's na nefureterectomie met curatieve intentie.

De Engelse onderzoekers hebben POUT - een fase III, open-label, gerandomiseerde gecontroleerde studie uitgevoerd bij  291 patiënten gehaald uit maar liefst 71 ziekenhuizen in het VK.

Zij kozen patiënten met UTUC nadat een robot gestuurde kijkoperatie van een nier - nefrodetectomie was uitgevoerd. De deelnemers werden gerandomiseerd (1: 1) toegewezen aan een surveillancegroep - wait-and-see (N = 129) en aan een groep (N = 132) die vier kuren van 21 dagen met chemotherapie kregen. Chemotherapie was ofwel cisplatin (70 mg / m2) of carboplatin intraveneus toegediend op dag 1 en gemcitabine (1000 mg / m2) intraveneus toegediend op dag 1 en 8; chemotherapie werd gestart binnen 90 dagen na de nieroperatie - nefrodetectomie.

Aanvullende chemotherapie verbeterde significant de ziektevrije overleving (hazard ratio 0,45, 95% BI 0,30 - 0,68; p = 0 0001) bij een mediane follow-up van 30-3 maanden (IQR 18 · 0–47 · 5). De ziektevrije percentages voor drie jaar zonder recidief waren respectievelijk 71% voor de chemotherapiegroep (95% BI 61–78) en 46% (36–56) voor de surveillancegroep.
55 (44 %) van de 126 deelnemers die chemotherapie hadden gehad hadden bijwerkingen van acute graad 3 of erger tijdens de behandeling. Deze bijwerkingen kwamen overeenkwamen met vaak gerapporteerde bijwerkingen voor dit chemotherapieschema. Vijf (4%) van de 129 patiënten uit de surveillancegroep, hadden acute graad 3 of erger optredende bijwerkingen. Er zijn geen behandelingsgerelateerde sterfgevallen gemeld.

Het volledige studierapport, gepubliceerd in The Lancet: Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial is gratis in te zien.

Hier het abstract van de studie:

. 2020 Apr 18; 395(10232): 1268–1277.
PMCID: PMC7181180
PMID: 32145825

Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial

Alison Birtle, MD,a,b,* Mark Johnson, MD,c John Chester, Prof, PhD,d Robert Jones, Prof, PhD,e David Dolling, PhD,f Richard T Bryan, PhD,g Christopher Harris,h, Andrew Winterbottom,i, Anthony Blacker, MBChB,j James W F Catto, Prof, PhD,k Prabir Chakraborti, MD,l Jenny L Donovan, Prof, PhD,m Paul Anthony Elliott, PhD,n Ann French, MSc,o Satinder Jagdev, MDRB,p Benjamin Jenkins, MSc,f Francis Xavier Keeley, Jr, MD,q Roger Kockelbergh, MBChB,r Thomas Powles, Prof, PhD,s John Wagstaff, Prof, MD,t Caroline Wilson, PhD,m Rachel Todd, MSc,f Rebecca Lewis, BSc,f and Emma Hall, Prof, PhDf

Summary

Background

Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs.

Methods

We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2–T4 pN0–N3 M0 or pTany N1–3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve 4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.govNCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants.

Findings

Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30–0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0–47·5). 3-year event-free estimates were 71% (95% CI 61–78) and 46% (36–56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported.

Interpretation

Gemcitabine–platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population.

Funding

Cancer Research UK.

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