BCa is the most common cancer in the urinary system followed the prostate cancer in males[1]. According to a population-based retrospective study, the mortality rate fluctuated slightly after the diagnosis of metastatic BCa without amelioration over the past few years [8]. From 1993 to 2000, the 5-year relative survival of AJCC stage IV BCa was only 17.4% based on the National Cancer DataBase [13]. Consequently, it is necessary to analyze the relationship between different metastatic pattern and overall survival in AJCC stage IV BCa patients
In our study, we found that: (1) bone and lung were the most common metastatic sites; (2) male patients outnumber females in stage IV; (3) squamous cell carcinoma was the poorest prognostic histological types; (4) T3 had better survival outcomes than any T stage; (5) on multivariate analysis, the primary tumor surgery, tumor size and histology were independent prognostic factors impacting the patients with distant metastasis.
The results of our study were aligned with previous research, bone and lung were the most common site of distant metastasis for BCa [9]. As for bone metastasis, the coexistence of both osteolytic and osteoblastic lesions can be observed [14]. If the bone metastatic lesions do not be treated properly, some skeletal-related events (SREs) would be occurred, which can make people debilitative [15, 16]. Those events include pathologic fractures, spinal cord compression, radiation therapy to bone, surgery to bone, and hypercalcemia of malignancy [17]. Kinnane et al. also concluded that the great mass of patients with bone metastasis would suffer one SRE at least without bone-targeted therapies [18]. From these above, bone-targeted treatments are inevitable in case of the occurrence of SREs. For lung, there are numerous studies revealed the association between lung metastasis and survival. Interestingly, no survival advantages were presented in metastasectomy [9]. Meanwhile, Luzzi et al. discovered that diameter of the metastatic lesions < 3 cm was an independent prognostic factor that possessed higher 5-year survival in lung metastasis [19].
On multivariate analysis, primary tumor site was an independent prognostic factor of OS (P < 0.05), with patients who suffered from tumor in ureteric orifice obtaining the shortest overall survival. This conclusion is consistent with the outcomes of Eric et al, which discovered that the patients with primary tumors involving the ureteral orifice had 12.9% recurrence rate of upper urinary tract. [20]. This phenomenon might be caused by the loss of the anti-reflux mechanism after resected the orifice, and thus the tumor cells seeded to the upper urinary tract [21]. However, Mano et al reported their outcomes in 65 patients, which revealed only one patient was diagnosed with recurrent tumor in the upper urinary tract after transurethral resection of bladder tumor from ureteral orifice, and their conclusion suggested that ureteral orifice resection was not very relevant with an increased risk of tumor recurrence in the upper urinary tract [22]. These outcomes disagree with the results of Eric et al. and us, which might be caused by the small number of patients.
Consistent with the results of other studies, primary surgery was a benefit for the survival of patients with locally advanced disease [23]. Nevertheless, only surgery does not curative enough for locally advanced and metastatic BCa patients [24]. As a chemosensitive tumor, adjuvant therapy as chemotherapy always be proceeded within the perioperative period. Herr et al. reported 80 underwent radicalcystectomy after chemotherapy, 24 of the 80 cases (30%) presented no active cancer [25]. Currently, open radical cystectomy (ORC) plus pelvic lymphadenectomy is the gold standard for high-grade invasive BCa and benefits local cancer control [26]. Meanwhile, laparoscopic radical cystectomy (LRC) is an alternative treatment for those patients, which can reduce morbidity in the perioperative period [27]. Robot-assisted radical cystectomy (RARC) has many considerable advantages, but there are some studies revealed that LRC and RARC have no obvious advantages on ORC in controlling postoperative complications [28, 29].
Notably, urachus is the rarest site of BCa in our study, which is consistent with what we now know from early literature [30, 31]. Adenocarcinomas is the most common pathological type of urachus malignancy [32]. In some earlier reports, because of the lack of effective treatment protocol, the 5-year survival rate of locally advanced urachus cancers was 43% [31]. With the progress in surgical techniques and adjuvant therapies in recent years, the 5-year survival rate has risen to 50% [33, 34]. Even so, urachal cancer exhibited a better prognosis than other types of bladder cancer whatever the order of initiation of tumor formation [35, 36].
To our knowledge, this is the first study focusing on the hematogenous metastatic pattern of BCa patients based on SEER database. Inevitably, there are obvious limitations due to the limited information of SEER database and the retrospective nature of this kind of study. First of all, the metastatic data to above 4 sites were provided since 2010 and follow-up time is not very long. Secondly, comparing to those patients with synchronous metastasis, metachronous metastasis may possess larger quantity. Besides, information on other metastatic sites is bland, such as upper urinary tract and adrenal gland. Moreover, laboratory parameters including alkali phosphatase, alanine transaminase could not acquire from SEER for assessing the influence of metastatic sites.