Review articleEndocavitary treatment for upper tract urothelial carcinoma: A meta-analysis of the current literature
Introduction
Upper tract urothelial carcinoma (UTUC) accounts for 5% of all urothelial cancers, with an estimated annual incidence of 1 to 2 cases per 100,000 [1]. UTUC exhibits aggressive clinical behavior with 5-year cancer-specific survival (CSS) rates varying from 10% to 70%, mainly depending on tumor stage and lymph-nodal status at diagnosis [2], [3], [4], [5]. To date, the standard treatment for nonmetastatic UTUC remains radical nephro-ureterectomy with bladder cuff excision. At some centers, perioperative cisplatin-based combination chemotherapy is administered followed by surgery with lymphadenectomy [6]. In recent years, a kidney-sparing approach to UTUC patients has become more acceptable with the aim of preserving renal function and preventing the long-term complications associated with chronic kidney disease, without compromising oncologic outcomes and surgical safety [7], [8]. To date, kidney-sparing surgery (KSS) is indicated in patients harboring a tumor size ≤2 cm, unifocal disease, low-grade cytology, low-grade cancer on ureteroscopic biopsy, and no evidence of invasion or extra-organ spread on computer tomography [6], [9], [10], [11], [12], [13].
In patients treated with KSS, recurrence in the upper and lower urinary tract is quite common, affecting 15% to 90% of patients, depending on the case mix and follow-up [14], [15]. Therefore, similar to the management of nonmuscle invasive bladder cancer (NMIBC), adjuvant endocavitary instillations have been proposed in patients treated with KSS, with the aim of reducing recurrence and progression rates in low risk papillary UTUCs and to treat upper tract (UT) carcinoma in situ (CIS); however, adjuvant endocavitary treatment is not routinely recommended by any national or international guidelines [6]. The evidence supporting the use of endocavitary instillations is scarce and mainly consists of small, single-center series, characterized by a relatively short follow-up, retrospective study design and the problems associated with reporting bias [16]. The widespread use of adjuvant instillations after KSS has been limited by concerns regarding the method of administration and the unsatisfactory oncologic results. The major challenge of adjuvant endocavitary treatment resides in specific anatomic and physiologic characteristics of the upper urinary tract which has no storage capacity and is bathes continuously by the downward flow of urine produced by the kidneys [14].
To overcome these limitations, novel methods such as slow-release formulations including stents and hydrogel polymers with reverse-thermal gelation properties (liquid at cold temperature and soft, adherent gel at body temperature) and mitomycin C (MMC) have been developed and tested in preclinical models [17], [18], [19]. The aim of this review and meta-analysis was to investigate the oncologic efficacy of endocavitary therapies for the treatment of UTUC to create an up-to-date reference point for comparison to these new methods of drug delivery. The primary endpoints of our study were endocavitary recurrence, progression, and mortality. Bladder recurrence was not assessed in this study.
Section snippets
Study eligibility
This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement [20]. The literature search was performed nonsystematically by 2 authors to identify studies investigating UT instillation therapies in UTUC patients. We searched PubMed and MEDLINE in June 2018 using the following string terms: (“UTUC” OR “urothelial carcinoma” OR “upper tract” OR “upper urinary tract”) AND (“instillation” OR “instillation therapy” OR “intracavitary
Results
We identified 27 eligible reports and included 18 studies for quantitative analyses. All included reports were nonrandomized observational analyses or case series with sample sizes ranging from 5 to 50 patients. All selected studies comprised a total of 438 participants who received UT instillation therapy for Ta, T1, or Tis UTUC. Among studies that reported on UT recurrence, 154 (35%) patients developed UT recurrence during a median follow-up of 30 months.
Discussion
In this pooled analysis, we investigated the oncologic outcomes (excluded bladder recurrence) of patients with papillary UTUC or CIS of the UT treated with KSS and adjuvant endocavitary treatment. We separately analyzed the therapeutic effect of adjuvant therapies (i.e., chemotherapeutic agents and/or immunotherapy with BCG) after KSS for papillary noninvasive (Ta-T1) UTUCs and of adjuvant BCG for the treatment of UT CIS.
We found no difference between the way of drug administration (antegrade
Conclusions
In this meta-analysis, we investigated the oncological outcomes of patients with noninvasive UTUC treated with endocavitary instillations. We found no differences between the type of drug used (MMC vs. BCG) for the adjuvant treatment of patients with Ta-T1 UTUC in terms of RFS, CSS, and OS. Moreover, both in patients with Ta-T1 UTUC and in those treated with BCG for UT CIS, no differences were found with regards to the type of approach used for instillations (antegrade vs. retrograde). Finally,
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