Nomogram for customized recurrence prediction in primary non-muscle-invasive bladder cancer based on routine blood and urine parameters

In this study, we evaluated the ability of the routine blood and urine parameters in predicating the recurrence of primary NMIBC. Specifically, higher age, blood platelet count, urinary leucocyte counts and lower urinary mucus filament showed significant associations with rapid NMIBC recurrence. Furthermore, we established a nomogram model, which comprised the parameters above and performed well in the customized prediction of NMIBC recurrence at 6th, 12th, 24th and 36th month, hypothesized that its predictive value would assist doctors in identifying high-risk NMIBC patients and providing suitable follow-up alternatives.

The current gold standards for BC follow-up are urine cytology and cystoscopy with biopsy. However, cystoscopy is intrusive, expensive, has an accuracy rate of 85–90%, and has a risk of urinary tract infection, hematuria, and inadequate adherence to care guidelines. Additionally, it can be challenging to schedule repeated postoperative cystoscopic follow-ups for patients with NMIBC.

An extensive effort has been made in recent years to find biomarkers in blood and urine that can be used to diagnose BC and predict how well patients will respond to treatment. Lower urine pH and greater levels of urine protein, urine glucose, and pee occult blood have been linked to an increased risk of BC, according to research by Zeng et al. [9]. When compared to healthy controls, patients with bladder cancer have greater levels of urine- and plasma-soluble proteins such as VEGF, endostatin, stress proteins, and cytokines, which aid in the detection and staging of the disease [10]. After BCG injection, leukocyte cell presence in urine appears to be a replacement urine biomarker of immune system activity [11]. Additionally, a worse response to neoadjuvant chemotherapy has been associated to an increased neutrophil to lymphocyte ratio in MIBC patients’ blood [12]. However, few studies have looked into the use of non-invasive markers in blood or urine to predict the prognosis of NMIBC patients. Elsawy et al. reported that urinary IL-10 and serum tumor necrosis factor-α (TNF-α) can significantly predict the initial complete response after BCG treatment in high-risk NMIBC [14]. Li et al. observed that the presence of ferrous protoporphyrin(+)/reactive oxygen species(+) in urine is associated with an increased risk of recurrence in newly diagnosed NMIBC patients [15].

The HALP score has been identified as a significant predictive factor in patients with various malignancies and is thought to be an easily computed index of systemic inflammation and nutritional status [8, 9]. It was clear from these observations that platelets might be an unfavorable risk factor, but hemoglobin, albumin, and lymphocytes may be favorable risk factors. For patients with MIBC undergoing radical cystectomy, HALP score was indicated as an independent predictive predictor [16, 17]. However, it is unknown whether the HALP can predict recurrence of NMIBC patients. In addition, platelets have been shown to interact with cancer cells and aid their survival and metastasis through different mechanisms. By accumulating platelets, tumor cells can escape from the human immune system. And platelets could protect tumors from TNF-α mediated cytotoxicity and the high shear forces which could potentially damage them in flowing blood [18, 19]. According to our findings, though HALP score has no significant correlation with the prognosis of NMIBC, blood platelet count was the independent predictive factors for disease recurrence.

Numerous epidemiological investigations have looked into the link between Urinary tract infections (UTIs) and the risk of BC. The majority of these investigations supported the idea that recurring UTIs increase the risk of BC in the future [20, 21]. Jhamb et al. [22] and Jiang et al. [23] indicate, in contrast to these results, a decreased risk of BC with an increase in kidney and bladder infections. Uncertainty still exists regarding the prognosis of NMIBC and UTIs. In this study, we measured whether infection associated urine parameters were related to the prognosis of BC, including urinary leucocyte counts, nitrite, protein, bacterium and mucus filament. The results demonstrated that lower urinary mucus filament were related to rapid NMIBC recurrence. Interestingly, those with higher urine leucocyte levels had a higher recurrence risk. Similarly, Wong et al. found that a greater lymphocyte count in MIBC patients’ urine was substantially linked with illness recurrence [24].

Due to its user-friendly interface and numerical probability, the nomogram has been frequently employed to generate prognostic information for the specific patient [25]. With the aid of multivariate Cox regression analysis, an unique nomogram was created in this work by combining age, blood platelet count, urinary leucocyte counts and lower urinary mucus filament. The combined nomogram worked well as an all-encompassing scoring system for predicting the recurrence of NMIBC, which was supported by the ROC curve, calibration curve and C-index. DCA curve also demonstrated positive net benefits in guiding clinical decisions. Anymore, after dividing the patients into groups with low- and high-risk score according to the nomogram, the group with a high-risk score recurred rapidly and had a bad prognosis.

Although newer methods like fluid biopsy and genetic testing seem to increase the accuracy of BC prognosis predictions, they have drawbacks including a hefty price tag and labor-intensive analysis [26,27,28]. The majority of them are also still through clinical studies. Age, blood platelet count, urine leucocyte counts, and lower urinary mucus filament are routinely evaluated and reported for hospitalized patients in clinical practice, therefore there was no added cost or patient annoyance. This study is limited by a small sample size, which must be increased for future validation.

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