Page 9 - Canadian Urological Association/Genitourinary Medical Oncologists of Canada consensus statement: Management of unresectable locally advanced and metastatic urothelial carcinoma

CUAJ – Consensus Statement Warren et al
Unresectable locally advanced and metastatic urothelial carcinoma

In UC of the bladder, clinical T4b disease is defined as a tumour which invades the pelvic
wall, abdominal wall or adjacent bowel / rectum and is unresectable unless significant
downstaging can be achieved. Clinical N1-2 disease consists of lymph node involvement in the
true pelvis, whereas N3 consists of common iliac lymph node involvement. Not all patients with
regional node involvement will have distant metastases, particularly with cN1-2 stage disease.
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th
The definition of nodal metastases changed in 2010 with the 7 edition of the AJCC. In prior
editions, common iliac lymph node involvement was considered to be metastatic and N1-3
defined nodes of varying number and size in the true pelvis.
Evidence defining the optimum treatment of cT4b and cN1-3 disease is limited to
retrospective series. These patients have been routinely excluded from neoadjuvant
chemotherapy trials, and in the Advanced Bladder Cancer meta-analysis of neo-adjuvant
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chemotherapy, represented only 1% and 4% of cases, respectively. Likewise, these patients
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have generally been excluded from chemoradiotherapy studies. Consequently the optimum
management of this subgroup of patients is not well defined.
A commonly used treatment paradigm in published series has consisted of induction
chemotherapy (IC) followed by RC or HDRT in select patients. 58–67 Several studies utilizing
this approach are outlined in table 3. Only the study by Nieuwenhuijzen required histological
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confirmation of involved lymph nodes. Radical cystectomy / PLND was the most commonly
used consolidation treatment with HDRT only utilized in a subset of patients in two studies. The
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study by Urakami included 29 patients with upper tract UC out of 60 patients. All other studies
were restricted to UC of the bladder. Most studies did not define specific selection criteria for
RC or HDRT, however the study by Nieuwenhuijzen required a response to induction
chemotherapy in order to proceed to RC and the study by Urakami selected patients with
responsive or stable disease. The study by Als had a unique design whereby patients who
obtained a CR based on both CT imaging and cystoscopy and biopsy underwent close
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surveillance whereas patients who had a partial response received either RC or HDRT.
Although the study by Herr did not define criteria for RC, 80 patients out of an initial 207 pts
receiving chemotherapy proceeded to RC, implying that patients were carefully selected for
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surgery. The study by Black evaluated cT4b patients who had achieved sufficient downstaging
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from IC to become resectable. Most studies administered 4 cycles of chemotherapy.
Results from the above studies demonstrate the potential for cure with reported 5 year cancer
specific survival (CSS) / OS ranging from 23 – 60%. On this basis, GUMOC considered it
reasonable to endorse the above treatment strategy for this group of patients. A further argument
for a curative treatment approach is the potential for inaccurate clinical staging of lymph nodes.
In studies of patients with cN1-3 who have proceeded directly to surgery a proportion have had
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pN0 disease implying false positive clinical staging. A benefit of commencing treatment with
IC is to spare patients who have significant disease progression the morbidity of surgery and / or
HDRT.