In United States, more than 80,500 cases were diagnosed as bladder cancer in 2019 year, which accounted for 4.6% of all cancer diagnoses [12]. Simultaneously, although women are at lower risk of bladder cancer than men, they should be taken seriously. At present, most studies focus on the overall prognosis after diagnosis of bladder cancer, however, reports on the prognosis and cause of death of patients who have undergone different surgical treatment were limited. There are significant differences between radical cystectomy and local tumor excision, including operative area and operative procedures [13]. For radical cystectomy, three options are available, including open radical cystectomy, traditional and robotic laparoscopy. Open radical cystectomy is considered to be the gold standard because of the stably long-term oncological outcomes, however, the characteristics of long time consuming, more blood loss, greater trauma, slow postoperative recovery and high complication rate make people strive for a more minimally invasive surgical method. Traditional laparoscopy can effectively decrease these perioperative risks because of minimally invasive approaches, nevertheless, four degrees of freedom of movement and poor ergonomics caused problems for surgeons. Compared with traditional laparoscopy, robotic surgery is characterized by the wider and clearer vision and more accurate and flexible control capability, but the high surgical cost and long learning curve make it controversial. The long-term oncological outcomes of the minimally invasive surgical methods are still under study [14,15,16,17]. A previous study [16] that involved 60 patients suggested that minimally invasive approaches could reach similar oncological outcomes to the open radical cystectomy by comparing the five-year recurrence-free survival, cancer-specific survival and overall survival of patients with bladder cancer who underwent different surgical methods. Moreover, the pathological types of bladder cancer are complex. These factors directly affect the economic burden, spiritual stress, quality of life and prognosis of patients. Hence, this emphasizes the requirements to optimize the selection of surgical methods and health management during survivorship. In our study, we assessed the cause of death after two surgical treatments of bladder cancer stratified by patient and tumor characteristics using representative population-based data from the United States. In female patients undergoing local tumor excision, approximately 50% death from non-tumor causes and 13.8% death from other malignant cancers, however, these women were overall less likely to die of most non-bladder cancer causes in comparison with the general population. In women undergoing radical cystectomy, nearly 82.2% of deaths occurred in 5 years after surgery, and compared with general population, the death of risk caused by non-bladder cancer significantly increased.
Patients with cancer usually have various comorbidities, and the status can directly affect the treatment decision-making, prognosis, and survival outcomes. It is reported that the severity of comorbidity status has a strong impact on the survival of patients in a dose-dependent fashion independent of cancer stage. Coexisting diseases can significantly increase the risk of the mortality of bladder cancer, and the influence degree of individual comorbidities and combined comorbidity is different. Simultaneously, the frequency and severity of perioperative complications increase with comorbidity rates increasing [18,19,20]. In our study, although the risk of death from heart diseases in all female patients who underwent surgery was slightly higher than that in the general population, it was the most common cause of death. Simultaneously, the ratio of cardiac death was continuously higher than the general population over all follow-up years after the surgery. According to the National Vital Statistics System statistics, 23.4% of the total United States population died of heart diseases in 2015 [21]. Considering these results, death caused by cardiovascular events should be concerned and relative risk factors should be monitored early, such as hyperlipidemia, cigarette smoking, and diabetes mellitus [22]. In patients who underwent radical cystectomy, the risk of death from septicemia was significantly increased in comparison with general population over all follow-up years. Nearly 2/3 of patients occur complications within 90 days after radical cystectomy, and the mortality rate ranges between 1.5% and 2% at 30 days postoperatively [20, 23]. Approximately 25% of the complications are infection, and obstruction caused by ureteral mesenteric anastomosis stenosis and urinary retention can lead to hydronephrosis, renal insufficiency and recurrent urinary tract infection [20]. Therefore, in the management of patients undergoing cystectomy, many long-term sequelae of urinary diversion should be considered, and the nursing of fistula, electrolyte balance and vitamin B12 should be monitored regularly [13]. The choice of the type of urinary diversion is crucial to the quality of life and prognosis of patients undergoing radical cystectomy. Failure of the urinary diversion may lead to the above-mentioned multiple complications and ultimately threaten the life of patients. The ideal urinary diversion should optimally maintain renal function, control urinary outflow, and minimize the incidence rate of patients. Among three types of urinary diversion, including orthotopic neobladders, cutaneous diversions and Ileal conduits, ileal conduits are considered to be the fastest, easiest, least complication-prone urinary diversion [24].
For patients with bladder cancer, age is considered to be an important prognostic factor. Compared with young patients, the mortality rate of elderly patients is higher because of poor histologies, higher recurrence rate, long-term accumulation of the molecular and genetic aberrations, accompanied by comorbidities and decreased immunity [25]. However, for patients undergoing radical cystectomy, it is reported that age is an important prognostic factor but is not irreplaceable, and tumor stage, grade and comorbidity status play decisive roles [26]. Our study showed that the risk of postoperative death in the 15–54 and 55–64 age groups, especially in the 15–54 age group, was significantly higher than that both in the other age groups and in the general population. This result seems different from previous studies, which believe that in contrast to those that occur in older patients, individuals under the age of 40 tend to express well-differentiated histologies and behave in a more indolent fashion [27, 28]. However, previous studies have not updated, and conducted detailed studies on patients after bladder cancer surgery. Young women who underwent surgical treatment, especially cystectomy, have high aggressive and rare pathological types and poor prognosis. However, further research is needed. Simultaneously, the risk of postoperative death in all races was higher than that in the general population, however, the risk of death in non-white patients was obviously higher. Previous study [25] suggested that compared to white females, fewer disease of African Americans with bladder cancer confine to the bladder, and present highly invasive, which may result from socioeconomic status, occupational exposures, smoking, and differences in metabolism of toxic substances. Moreover, in addition to the primary bladder cancer, the death caused by other malignant cancers should also raise concern. The change of hormone level in female patients after operation, or the subsequent treatment, including chemotherapy and immunotherapy, will make the patients in a low immune status, and the combination of other malignant cancers will significantly increase the mortality of patients, especially those who have undergone radical cystectomy [29,30,31].
The prognosis of patients with bladder cancer is relatively poor, especially women. Female patients are usually diagnosed with more advanced tumors at presentation and have less satisfactory outcomes after treatment with higher cancer-specific mortality. Therefore, multimodal management strategies play important roles in the survival and prognosis of bladder cancer patients, which require the cooperation of multidisciplinary teamwork to take charge of the whole process management of bladder cancer patients, including urology, radiotherapy, oncology, pathology, imaging, nuclear medicine, intervention, anesthesia, nursing and psychotherapy. In addition, personalized treatment and follow-up strategies for different individuals also play an irreplaceable role in multimodal management, including the selection of surgical approaches, the choice of radiotherapy, chemotherapy and immunotherapy at different stages, the improvement of perioperative surgical management, molecular-based systemic treatment strategies, accurate tumor burden assessment, and optimized follow-up policies. Moreover, the progress of molecular tumor biology, the modern research of tumor metastasis, and the development of different approaches has the potential to improve substantially the oncological outcomes [32, 33].
Despite the useful findings of our study, several limitations in our study are as follows: first, some important data lost due to lack of collection in SEER, such as smoking, which has been proved to be a risk factor for bladder cancer prognosis [34]. In addition, this study was based on the classification of surgical methods, which enables us to understand the role of surgical modality in the long-term survival of bladder cancer. However, the non-surgical treatment of bladder cancer is also important for the prognosis of patients. Moreover, different surgeons may have respective treatment strategies for bladder tumors of the same grade. The option of treatment and follow-up methods based on the surgeon's judgment of the final results and the choice of the type of technique proposed will directly affect the prognosis of patients. Finally, the retrospective nature of the SEER database used in the study may have, to an extent, weaken the conclusion.
In summary, this study provides contemporary and comprehensive evaluation of causes of death for female patients of bladder cancer who have underwent radical cystectomy or local tumor excision. We found that the overall risk of death significantly increased for female patients undergoing radical cystectomy or local tumor excision in comparison to the general population, and especially in patients undergoing radical cystectomy. Simultaneously, bladder cancer remains the leading cause of death after surgery, but the death caused by heart diseases could not be ignored, and for patients undergoing radical cystectomy, the death of risk caused by non-bladder cancer significantly increased compared with patients undergoing local tumor excision, such as septicemia. These data highlight the need for general primary care for these female patients during postoperative cancer survivorship.