This case demonstrates the advantage of adequate surgical extirpation (with appropriate margins) in addition to adjuvant chemotherapy as a means for oncologic control of MIBC with SV histological changes. Historically, evidence has supported the sarcomatoid variant urothelial carcinoma of the bladder (SV-UCB) to be a negative prognostic indicator. A cohort study of 46,515 patients with urothelial carcinoma (UC) through the Surveillance, Epidemiology, and End Results (SEER) database program in 2007 was reviewed to demonstrate patients with sarcomatoid carcinoma of the bladder presented at a more advanced disease stage as well as have a greater risk for death after adjusting for tumor stage on presentation [5]. Confirmed again in 2010, the SEER program was analyzed to identify a cohort of 221 patients specifically with SV-UCB, results demonstrating that SV-UCB presents as high grade, advanced disease with poor prognosis. The 1-, 5-, and 10-year cancer specific survival rates were 53.9%, 28.4%, and 25.8% respectively [11]. This is a stark contrast to outcomes of radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) with reported 5- and 10- year cancer free survival rates at 66% and 68% respectively [12]. However more recent data from 1,067 and 624 patient samples with MIBC cancer treated by single tertiary care centers failed to associate the sarcomatoid variant with a negative effect on survival after RC [13, 14]. These cohort studies represented data that included 21 and 15 cases of SV-UCB respectively between the tertiary care centers, corroborating the paucity of this variant histology. Hence, the current body of data is limited and inconsistent, precluding full understanding of the disease with relevant randomized controlled trials (RCTs) to establish a gold standard of care.
Previous evidence has recommended forgoing intravesical therapy in patients with SV T1 disease and proceeding directly to RC [15]. However, the morbidity of RC compared to bladder preserving approaches may be prohibitive for certain patients, such as the elderly population [16]. We are therefore motivated to investigate partial cystectomy (PC) as an additional option to manage variant histology urothelial carcinoma while preserving adequate bladder and sexual function [17]. For patients with a solitary lesion amenable to resection, PC allows the surgeon to assess tumor margins completely as well as perform a pelvic lymph node dissection (PLND) as needed. Published data from the SEER program registry for stage T1-T2 tumors with variant histology demonstrated no difference in cancer specific or overall mortality on cox regression modeling between PC and RC for the treatment of variant histology UC [18]. Though one limitation regarding partial cystectomy, as highlighted in this case, is the need for frequent surveillance cystoscopy due to the higher rate of recurrence within native urothelium. Our patient had one recurrence of a small low grade Ta UCB 21 months after PC.
Another consideration is the role of pelvic lymph node dissection (PLND) at the time of PC, as performed in this case. A SEER program query published in 2020 on patients with nonmetastatic pT2-T3 UC of the bladder treated by partial cystectomy discovered only 50% of patients treated by PC concomitantly received PLND. However, the results noted a 5-year case specific mortality of 30% for patients who received PLND compared to 41% for those who did not (p < 0.01) [19]. Though this corroborates the utility of PLND for nonmetastatic MIBC, the data is scarce regarding the utility of PLND for variant histology, particularly sarcomatoid variant UC.
Endoscopic management as a bladder preserving option for sarcomatoid variant UC has demonstrated inferior overall survival compared to RC [20]. However, Trimodal therapy (TMT) with maximal TURBT, sensitizing chemotherapy, and radiation therapy has been validated as a bladder preserving solution for MIBC in appropriate patient populations [21, 22]. However, no randomized comparison exists to compare radical cystectomy to TMT in the management of UC with variant histology. A recent review of 303 patients with MIBC treated by TMT demonstrated the 5 year survival of pure urothelial carcinoma at 75%, yet with a small sample size of SV-MIBC (n = 8), no statistically significant difference was found on subgroup analysis compared to the reported 5 year survival rate of 56% in the sarcomatoid variant pathology (p = 0.7) [23].
The presented patient was not considered for neoadjuvant chemotherapy as the transurethral resection of bladder tumor (TURBT) specimen demonstrated no evidence of muscle invasion and no published data exists to validate a survival benefit with neoadjuvant chemotherapy for treatment of T1 bladder cancer with SV histology, a contrast from evidence for muscle invasive or metastatic disease. A National Cancer Database study published on patients with non-metastatic MIBC (T2a-T4) demonstrated neoadjuvant chemotherapy improved overall survival and pathological downstaging compared to radical cystectomy alone for patients with SV UC (n = 501, p = 0.014) [24]. Another SEER registry review of 110 patients with metastatic SV UC reported an overall survival of 8 months with chemotherapy treatment and 2 months without (p = 0.016) [25]. Thus. the role of chemotherapy continues to be investigated for the management of SV UCB.
Current American Urological Association (AUA) expert opinion guidelines for non-metastatic MIBC with variant histology recommend for a divergence from standard evaluation and management [26]. There is currently no evidence-based consensus for a single appropriate chemotherapy regimen for SV histology. A meta-analysis involving 10 RCTs in patients treated with adjuvant chemotherapy after RC for MIBC (n = 1,183) demonstrated an absolute 11% improvement in recurrence free survival (p < .001) compared to RC alone [27]. In the presented case, four doses of adjuvant doxorubicin were administered after confirmation of muscle invasive disease on final pathology. A study by Sui et al. compared RC alone (n = 106), RC and either chemo- or radiotherapy (n = 71), TURBT alone (n = 146), and TURBT with chemo- or radiotherapy (n = 71) for the treatment of SV UC. Findings validated patients with radical cystectomy and some form of multimodal therapy demonstrated the best overall survival [20]. In addition to the mounting evidence within the literature, this case serves as an anecdotal example to justify the utility for chemotherapy in the treatment of SV-MIBC.
A limitation of this study is the presented utility for partial cystectomy as a potential management solution for sarcomatoid variant pT2 urothelial carcinoma is garnered from a single case report. Cohort studies are necessary to delineate oncologic and functional long-term outcomes. Future research endeavors ought to also assess the role of immunotherapy as the sarcomatoid transformation is associated with high PD-L1 expression [28], and a recent retrospective review of 755 patients with advanced or metastatic disease noted an improved complete response rate for patients with Sarcomatoid UC (52.6%) compared to pure UC (21.1%) after treatment with pembrolizumab (p = 0.032) [29].