Predictive ability of the geriatric 8 screening tool for treatment completion of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin therapy in patients with urothelial carcinoma

Abstract

Background

Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) therapy is expected to provide superior therapeutic efficacy compared to gemcitabine and cisplatin therapy as systemic chemotherapy for urothelial carcinoma. However, its high incidence of adverse events raises concerns about tolerability, particularly in older patients. This study evaluated the utility of the Geriatric 8 (G8) screening tool in patients undergoing dd-MVAC therapy and assessed its association with treatment progress.

Methods

A retrospective analysis was conducted on 65 patients with urothelial carcinoma who received dd-MVAC therapy between August 2018 and May 2023, with the goal of completing six treatment cycles. The G8 score was evaluated before treatment initiation, and its association with treatment completion and adverse events was examined.

Results

The median age of patients was 71 years (range, 43–84 years), with 65% male and 35% female. The median pretreatment G8 score was 13 (range, 7–17). Patients with a G8 score ≥14 demonstrated a significantly higher six-cycle treatment completion rate than those with a G8 score <14 (87% vs. 60%, P = 0.026). The incidence of adverse events did not differ between the groups. Furthermore, among various clinicopathological factors, the G8 score was identified as an independent predictor of six-cycle treatment completion (odds ratio: 0.17, P = 0.021), along with Eastern Cooperative Oncology Group Performance Status.

Conclusion

Pretreatment G8 scores were associated with the treatment completion rates of dd-MVAC therapy.

The pretreatment G8 score predicts the completion of dd-MVAC therapy in patients with urothelial carcinoma and may assist in identifying those likely to tolerate this intensive chemotherapy.

Introduction

The proportion of older patients with cancer is steadily increasing in Japan [1], making the management of these patients undergoing invasive and high-risk therapies, such as surgery or chemotherapy, increasingly important. Older patients often exhibit greater vulnerability and frailty, which significantly affect their tolerance to standard oncological treatments. Therefore, it is desirable to perform a geriatric assessment (GA), in addition to standard oncological evaluation, to better predict treatment outcomes, adverse events (AEs), and functional decline in this patient population [2–4].

Among the various available GA tools, the Geriatric 8 (G8) screening tool is widely recognized as a simple and validated instrument for identifying frailty and predicting treatment-related risks in older patients with cancer [5–10]. The G8 is an 8-item screening tool with scores ranging from 0 (severely impaired) to 17 (not at all impaired), and a cut-off value of ~14 is considered appropriate [5]. Previously, we reported that the G8 assessment could serve as an effective predictor of prolonged length of hospital stay and postoperative complications in patients undergoing urological surgery [11].

Effective management of AEs is essential during chemotherapy to maintain adequate treatment delivery and completion. Based on a large-scale meta-analysis, recently published guidelines recommend the incorporation of GA into clinical practice, indicating that GA-guided patient management can reduce chemotherapy-related AEs and improve treatment completion rates [12].

Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) chemotherapy is an established systemic regimen for advanced urothelial carcinoma [13,14]. The VESPER trial demonstrated that neoadjuvant chemotherapy with dd-MVAC provided a superior pathological response and prolonged progression-free and overall survival compared to gemcitabine and cisplatin therapy [15–17]. Regarding toxicity profiles, dd-MVAC with granulocyte-colony stimulating factor support was associated with lower incidences of leukopenia and febrile neutropenia than conventional MVAC therapy [14], but exhibited higher incidences of anemia, asthenia, and gastrointestinal symptoms than gemcitabine and cisplatin therapy [15]. However, few detailed reports have examined the association between geriatric assessments such as the G8 and specific dd-MVAC chemotherapy outcomes, including adverse event profiles and treatment completion rates.

In a previous study, we demonstrated that a dose-adjusted dd-MVAC regimen based on renal function and significant AEs showed promising results in achieving completion of scheduled treatments [18]. Therefore, the present study aimed to investigate the association between baseline G8 scores and treatment progress, treatment completion rates, and treatment-related AEs in patients receiving dd-MVAC chemotherapy.

Patients and methods

Patients

This retrospective study included patients with urothelial carcinoma who received dd-MVAC chemotherapy at the University of Tokyo Hospital and Teikyo University Hospital between August 2018 and April 2023. The study was approved by the Institutional Review Boards of the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo (approval number: 2024246NI), and Teikyo University School of Medicine. Informed consent was obtained using an opt-out approach.

Protocol of dd-MVAC

The detailed protocol has been previously described [18]. In brief, the dose-adjusted dd-MVAC regimen consisted of methotrexate (30 mg/m² on day 1), vinblastine (3 mg/m² on day 2), doxorubicin or pirarubicin (30 mg/m² on day 2), cisplatin (70 mg/m² on day 2), and pegfilgrastim (3.6 mg per body on day 4), administered every 2 weeks for six cycles. The initial doses of methotrexate and cisplatin were reduced to 75% of their full dose, with resumption of full dosing from the second cycle only if no severe AEs occurred. Dose modifications were based on renal function estimated using the Cockcroft-Gault formula. All chemotherapy doses were reduced by 20% if severe AEs, defined as non-hematologic grade ≥ 3 toxicities, hematologic grade 4 toxicities, febrile neutropenia, or hemorrhagic thrombocytopenia, were encountered. Patients were hospitalized until day 3 of each cycle and subsequently managed as outpatients. Inclusion criteria required an adequate performance status, with creatinine clearance ≥ 30 mL/min, white blood cell counts ≥ 2,500/μL, platelets ≥ 100,000/μL, and hemoglobin levels ≥ 8.0 g/dL. Treatment delays of up to 14 days were allowed to facilitate bone marrow recovery. Tumor response was evaluated using computed tomography after cycles 3 and 6, based on the Response Evaluation Criteria in Solid Tumors version 1.1. Chemotherapy was discontinued in the event of disease progression or if severe AEs adversely affected the patient’s condition.

Data collection

The G8 score was routinely assessed prospectively by the physician prior to the initiation of dd-MVAC therapy, using a patient-completed questionnaire and direct patient interviews, and was documented in the medical record. Clinicopathological characteristics of the patients at the start of dd-MVAC therapy, treatment delivery, toxicities, and pathological responses in the neoadjuvant cohort were extracted from medical records. The relative dose intensity of the chemotherapeutic agents was calculated based on the administered dose and interval between cycles. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Statistical analyses

The association between clinicopathological factors at the initiation of dd-MVAC therapy and the inability to complete six treatment cycles was evaluated using nominal logistic regression analysis. Laboratory cutoff values for the data were defined based on the upper or lower limits of normal at each participating institution. Continuous variables were compared using the Mann–Whitney U test or Student’s t-test. The Kruskal–Wallis test was applied for nonparametric comparisons among the three groups. Categorical variables were evaluated using Fisher’s exact test. All statistical analyses were performed using R version 4.2.3 (R Core Team, R Foundation for Statistical Computing, Vienna, Austria) and RStudio version 2023.12.0+369 (RStudio Team, RStudio, PBC, Boston, MA, USA). P values of < 0.05 were considered statistically significant.

Results

Patients’ characteristics

The clinical characteristics of patients at the initiation of dd-MVAC therapy are summarized in Table 1. The cohort consisted of 65 patients, including 42 men (64.6%) and 23 women (35.4%), with a median age of 71 years (range, 43–84 years). Primary lesions were located in the lower urinary tract in 38 patients (58.5%), the upper urinary tract in 26 patients (40.0%), and both sited in one patient (1.5%). The chemotherapy regimens included neoadjuvant (26 patients, 40.0%), adjuvant (12 patients, 18.5%), and salvage (27 patients, 41.5%) therapies. The G8 ≥ 14 group comprised 23 patients, whereas the G8 < 14 group included 42 patients. The only significant difference between the two groups was in body mass index (P = 0.008), with a median of 23.9 kg/m² in the G8 ≥ 14 group and 21.8 kg/m² in the G8 < 14 group.

Table 1.

Patients’ characteristics at the start of dd-MVAC.

Factors	All cases n = 65	G8 ≥ 14 n = 23	G8 < 14 n = 42	P value
Age, years, median (range):	71 (43–84)	71 (53–82)	70.5 (43–84)	0.36a
Age, years, n (%):
< 75	45 (69.2%)	15 (65.2%)	30 (71.4%)	0.76c
75–79	12 (18.5%)	6 (26.1%)	6 (14.3%)
≥ 80	8 (12.3%)	2 (8.7%)	6 (14.3%)
Sex, n (%):
Male	42 (64.6)	18 (78.3)	24 (57.1)	0.11b
Female	23 (35.4)	5 (21.7)	18 (42.9)
BMI, kg/m2, median (range):	22.7 (14.6–31.0)	23.9 (19.1–30.5)	21.8 (14.6–31.0)	0.008*a
BMI, kg/m2, n (%):
< 18.5	8 (12.3%)	0 (0%)	8 (19%)	0.035*c
18.5–25	45 (69.2%)	17 (73.9%)	28 (66.7%)
≥ 25	12 (18.5%)	6 (26.1%)	6 (14.3%)
ECOG PS, n (%):
0	55 (84.6)	19 (82.6)	36 (85.7)	0.78c
1	9 (13.8)	4 (17.4)	5 (11.9)
2	1 (1.5)	0 (0)	1 (2.4)
Comorbidity, n (%):
Hypertension	28 (43.1)	10 (43.5)	18 (42.9)	1.00b
Diabetes mellitus	6 (9.2)	2 (8.7)	4 (9.5)	1.00b
Hyperlipidemia	22 (33.8)	8 (34.8)	14 (33.3)	1.00b
Number of medications, n (%):
≤ 3	32 (49.2)	15 (65.2)	17 (40.5)	0.072b
≥ 4	33 (50.8)	8 (34.8)	25 (59.5)
History of smoking, n (%):
Never	20 (30.8)	4 (17.4)	16 (38.1)	0.71c
Past	30 (46.2)	16 (69.6)	14 (33.3)
Current	15 (23.1)	3 (13.0)	12 (28.6)
Primary site, n (%):
Lower urinary tract	38 (58.5)	13 (56.5)	25 (59.5)	0.71c
Upper urinary tract	26 (40.0)	9 (39.1)	17 (40.5)
Both	1 (1.5)	1 (4.3)	0 (0)
Histology of primary site, n (%):
Pure UC	53 (81.5)	17 (73.9)	36 (85.7)	0.32b
Others	12 (18.5)	6 (26.1)	6 (14.3)
Metastasis, n (%):
No	42 (64.6)	16 (69.6)	26 (61.9)	0.60b
Yes	23 (35.4)	7 (30.4)	16 (38.1)
Setting of chemotherapy, n (%):
Neoadjuvant	26 (40.0)	8 (34.8)	18 (42.9)	0.64c
Adjuvant	12 (18.5)	5 (21.7)	7 (16.7)
Salvage	27 (41.5)	10 (43.5)	17 (40.5)
Laboratory data, median (range):
White blood cells (103/μl)	6.4 (2.6–19.8)	6.2 (2.6–13.7)	6.6 (3.5–19.8)	0.32a
Hemoglobin (g/dL)	11.8 (8.0–16.1)	12.2 (8.7–14.4)	11.6 (8.0–16.1)	0.32a
Platelets (104/μl)	26.9 (15.5–76.4)	25.5 (18.8–54.9)	27.6 (15.5–76.4)	0.24a
Albumin (g/dL)	3.8 (2.1–4.6)	3.7 (2.4–4.4)	3.9 (2.1–4.6)	0.48a
Creatinine (mg/dL)	0.90 (0.48–1.65)	1.05 (0.51–1.65)	0.87 (0.48–1.51)	0.13a

^*Statistically significant. ^aMann–Whitney U test. ^bFisher's exact test. ^cKruskal–Wallis test. dd-MVAC, dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin; G8, Geriatric-8; BMI, body mass index; ECOG PS, Eastern Cooperative Oncology Group Performance Status; UC, urothelial carcinoma.

Treatment delivery

A total of 45 patients (69.2%) completed six scheduled cycles of dd-MVAC therapy (Table 2). The G8 ≥ 14 group demonstrated a significantly higher completion rate than the G8 < 14 group (87.0% vs. 59.5%, P = 0.026; Figure 1). No significant differences were observed in the reasons for treatment discontinuation (Table 2). Similarly, no differences were observed in the number of patients who underwent full-dose escalation or relative dose intensity.

Table 2.

Treatment delivery of dd-MVAC.

Parameters	All cases   n = 65	G8 ≥ 14   n = 23	G8 < 14   n = 42	P value
Cycles of dd-MVAC, n (%):
Completing 6 cycles	45 (69.2)	20 (87.0)	25 (59.5)	0.026*a
Not completing 6 cycles	20 (30.8)	3 (13.0)	17 (40.5)
Reasons for not completing 6 cycles, n (%):
Non-hematological AEs	8 (40.0)	2 (8.7)	6 (14.3)	0.70a
Progression disease	5 (25.0)	0 (0)	5 (11.9)	0.15a
Hematological AEs	4 (20.0)	1 (4.3)	3 (7.1)	1.00a
Other reasons	3 (15.0)	0 (0)	3 (7.1)	0.55a
Days per course, mean ± SD:	15.6 ± 2.0	15.7 ± 2.4	15.6 ± 1.9	0.78b
Increase to full dose, n (%):
Yes	18 (27.7)	5 (21.7)	13 (31.0)	0.57a
No	47 (72.3)	18 (78.3)	29 (69.0)
Relative dose intensity, %, mean ± SD:
Methotrexate	60.0 ± 19.6	59.6 ± 18.3	60.3 ± 20.5	0.88b
Vinblastine	83.6 ± 15.6	83.9 ± 16.4	83.5 ± 15.3	0.93b
Doxorubicin	83.6 ± 15.6	83.9 ± 16.4	83.5 ± 15.3	0.93b
Cisplatin	62.2 ± 19.6	62.3 ± 18.6	62.1 ± 20.3	0.97b

^*Statistically significant. ^aFisher's exact test. ^bStudent's t-test. dd-MVAC, dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin; G8, Geriatric-8; AE, adverse event; SD, standard deviation.

Figure 1.

Percentage of dd-MVAC therapy cycles completed in the G8 ≥ 14 and G8 < 14 groups. Dd-MVAC, dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin.

Adverse events

Table 3 summarizes the CTCAE grade ≥ 3 AE profile. Grade ≥ 3 AEs were observed in 22 patients (95.7%) in the G8 ≥ 14 group and 36 patients (85.7%) in the G8 < 14 group. No significant differences were observed in the incidence of hematological or non-hematological AEs between the two groups.

Table 3.

CTCAE grade ≥ 3 adverse events

Events	All cases n = 65	G8 ≥ 14 n = 23	G8 < 14 n = 42	P value a
Any AEs, n (%):	58 (89.2)	22 (95.7)	36 (85.7)	0.41
Hematological AEs, n (%):
Any	58 (89.2)	22 (95.7)	36 (85.7)	0.41
Neutropenia	45 (69.2)	17 (73.9)	28 (66.7)	0.59
Leukopenia	40 (61.5)	16 (69.6)	24 (57.1)	0.43
Anemia	32 (49.2)	10 (43.5)	22 (52.4)	0.61
Thrombocytopenia	23 (35.4)	8 (34.8)	15 (35.7)	1.00
Febrile neutropenia	9 (13.8)	4 (17.4)	5 (11.9)	0.71
Required treatment
Red blood cell transfusion	28 (43.1)	8 (34.8)	20 (47.6)	0.43
Filgrastim administration	11 (16.9)	6 (26.1)	5 (11.9)	0.18
Platelet transfusion	5 (7.7)	2 (8.7)	3 (7.1)	1.00
Non-hematological AEs, n (%):
Any	28 (43.1)	12 (52.2)	16 (38.1)	0.30
Anorexia	13 (20.0)	5 (21.7)	8 (19.0)	1.00
Fatigue	12 (18.5)	3 (13.0)	9 (21.4)	0.52

^*Statistically significant. ^aFisher's exact test. CTCAE, Common Terminology Criteria for Adverse Events; G8, Geriatric-8; AE, adverse event.

Analysis of factors involved in failure to complete six cycles

The results of the correlation analysis between clinicopathological factors at the initiation of dd-MVAC therapy and the inability to complete six cycles are presented in Table 4. In the univariable analysis, an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥ 1 (odds ratio: 0.23; 95% confidence interval: 0.06–0.93; P = 0.039) and a G8 score < 14 (odds ratio: 0.22; 95% confidence interval: 0.06–0.86; P = 0.030) were significantly associated with failure to complete six cycles of dd-MVAC. In the multivariable analysis, both factors remained significantly associated with the failure to complete six cycles of dd-MVAC.

Table 4.

Analysis of factors at the initiation involved in completion of 6 cycles of dd-MVAC therapy.

Factors	Reference	Univariable		Multivariable
		OR (95% CI)	P value	OR (95% CI)	P value
Age	Continuous	1.00 (0.95–1.06)	0.93
Age, years, ≥ 75	< 75	0.75 (0.25–2.32)	0.62
Age, years, ≥ 80	< 80	0.71 (0.15–3.30)	0.66
Sex, female	Male	2.00 (0.62–6.47)	0.25
BMI	Continuous	0.99 (0.85–1.15)	0.87
BMI, kg/m2, ≥ 18.5	< 18.5	2.56 (0.57–11.5)	0.22
BMI, kg/m2, ≥ 25	< 25	0.86 (0.23–3.29)	0.83
ECOG PS, ≥ 1	0	0.23 (0.06–0.93)	0.039*	0.16 (0.03–0.80)	0.026*
Comorbidity
Hypertension, yes	No	1.20 (0.41–3.50)	0.74
Diabetes mellitus, yes	No	2.38 (0.26–21.8)	0.44
Hyperlipidemia, yes	No	0.68 (0.23–2.02)	0.49
Cardiovascular diseases, yes	No	0.74 (0.19–2.87)	0.66
Number of medications, ≥ 4	≤ 3	0.78 (0.27–2.25)	0.65
History of smoking, past	Never	1.41 (0.39–5.05)	0.60
History of smoking, current	Never	0.49 (0.12–1.97)	0.32
G8 score, < 14	≥ 14	0.22 (0.06–0.86)	0.030*	0.17 (0.04–0.76)	0.021*
Primary site, upper tract or both	Lower tract	0.61 (0.21–1.76)	0.36
Histology, not pure UC	Pure UC	2.57 (0.51–13.0)	0.25
Metastasis, yes	No	0.75 (0.25–2.23)	0.60
Setting of chemotherapy, adjuvant	Neoadjuvant	0.33 (0.07–1.50)	0.15
Setting of chemotherapy, salvage	Neoadjuvant	0.40 (0.12–1.41)	0.16
Laboratory data
White blood cells	Continuous	1.00 (1.00–1.00)	0.064
Hemoglobin	Continuous	1.07 (0.80–1.42)	0.67
Platelets	Continuous	0.99 (0.95–1.03)	0.64
Albumin	Continuous	1.59 (0.60–4.25)	0.36
Creatinine	Continuous	1.31 (0.19–8.94)	0.78

Nominal logistic regression analysis. ^*Statistically significant. dd-MVAC, dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin; OR, odds ratio; CI, confidence interval; BMI, body mass index; ECOG PS, Eastern Cooperative Oncology Group Performance Status; UC, urothelial carcinoma; G8, Geriatric-8.

Comparison of the scores for each G8 item between the two groups

Table 5 presents a comparison of individual G8 item scores between the G8 ≥ 14 and G8 < 14 groups. Among the eight G8 items, the scores for four items, including food intake (P = 0.028), weight loss (P = 0.001), body mass index (BMI, P = 0.001), and self-rated health status (P < 0.001), showed statistically significant differences between the two groups.

Table 5.

Comparison of the scores of each G8 item between the groups.

G8 items	G8 ≥ 14 n = 23	G8 < 14 n = 42	P value a
	mean score ± SD
Food intake in the last 3 months	2.00 ± 0.00	1.74 ± 0.59	0.028*
Weight loss during the last 3 months	2.65 ± 0.57	1.52 ± 1.33	0.001*
Mobility	2.00 ± 0.00	1.86 ± 0.52	0.20
Neuropsychological problems	2.00 ± 0.00	1.86 ± 0.52	0.20
BMI	2.57 ± 0.73	1.62 ± 1.17	0.001*
Takes more than 3 medications per day	0.65 ± 0.49	0.40 ± 0.50	0.059
Self-rated health status	1.20 ± 0.60	0.58 ± 0.61	< 0.001*
Age	1.91 ± 0.29	1.86 ± 0.35	0.52

^*Statistically significant. ^aMann–Whitney U test. G8, Geriatric-8; SD, standard deviation; BMI, body mass index.

Discussion

We revealed a significant association between G8 scores before initiating dd-MVAC chemotherapy and treatment completion rates. Our previous findings indicated that high treatment completion rates could be achieved in Japanese patients receiving dd-MVAC, despite its poor tolerability, through dose adjustments based on renal function and AE profiles [18]. The present study builds on this evidence by demonstrating that G8 tool-based GA predicts treatment completion rates. These findings underscore the importance of incorporating GA into biochemical evaluations, particularly for older patients.

Numerous studies have investigated the relationship between GA and cancer treatment outcomes. The G8 score is useful in predicting OS [19,20], whereas randomized controlled trials have demonstrated that interventions based on comprehensive GA (CGA) reduce the incidence of AEs [21–24]. Based on these findings, CGA is recommended in clinical guidelines, including those issued by the American Society of Clinical Oncology, as a strategy for improving treatment outcomes in older patients with cancer [12].

A notable study by Rier et al. evaluated the association between G8 scores and chemotherapy completion rates in a prospective single-center cohort involving various tumor types [25]. Multivariable analysis identified age and G8 score as independent predictors of early chemotherapy discontinuation. However, of the 121 patients with solid tumors, 77 had colorectal cancer and only three had urothelial carcinoma. Furthermore, the study found that the G8 score predicted overall survival in patients with solid tumors but not in those with hematologic malignancies. These discrepancies may be attributed to differences in tumor biology, patient demographics, cancer types, and chemotherapy regimens. Therefore, the present study, which focused exclusively on urothelial carcinoma and used a single chemotherapy regimen, may more accurately reflect the clinical relevance of G8 scores in this specific context.

Interestingly, age was not significantly associated with early discontinuation of chemotherapy in the present study. Instead, the ECOG PS and G8 scores emerged as significant factors. This finding reinforces the importance of CGA, which evaluates not only physical function but also cognitive function, mental health, and medication management, as previously reported. Additionally, although only 10 patients (15.3%) in the present cohort had an ECOG PS of ≥ 1, 42 patients (64.6%) had a G8 score of < 14. This discrepancy suggests that physicians may have assessed chemotherapy tolerance primarily based on observable physical performance, potentially leading to the exclusion of patients with a poor ECOG PS. Conversely, the data indicate that some patients who appear physically fit may still be vulnerable to chemotherapy. The G8 score serve as a valuable tool for identifying such latent frailty. These findings emphasize the utility of incorporating G8-based assessments in clinical decision-making for older patients with cancer undergoing chemotherapy.

Among the items included in the G8 screening tool, the scores for factors primarily related to sarcopenia, such as reduced food intake, weight loss, and low BMI, showed significant differences between the G8 < 14 and G8 ≥ 14 groups. This finding aligns with previous reports demonstrating a strong association between sarcopenia and urothelial carcinoma [26]. Moreover, it is noteworthy that significant differences were observed not only in objective parameters but also in self-rated health status, a subjective measure. While BMI alone was not associated with the completion rate of dd-MVAC chemotherapy, the G8 score demonstrated a significant correlation, thereby emphasizing the utility of the G8 screening tool, which provides a comprehensive assessment across multiple domains, including self-rated health status.

This study has several limitations. First, this was a retrospective study with a relatively small sample size. Second, only patients deemed eligible for dd-MVAC therapy by the attending physicians were included, and only one patient had an ECOG PS of ≥ 2, introducing potential selection bias. Third, our population was relatively young and included patients aged < 70 years. The G8 has been validated in older patients with cancer, typically defined as ≥ 70 or 65 years [5]. However, since many patients undergoing dd-MVAC chemotherapy are frail carriers even at relatively young ages, we considered that it would be more valuable to evaluate the entire population of these patients, including those aged < 70 years. Fourth, the initial dose of methotrexate and cisplatin was routinely reduced to 75% of the full dose. This dose-reduction strategy was established based on previous findings [18], which demonstrated that AEs such as gastrointestinal symptoms often necessitated the termination of treatment in several patients after the first cycle of full-dose administration. However, starting all patients on a reduced dose could underestimate the efficacy and toxicity profiles of full-dose dd-MVAC. Fifth, the cohort included patients receiving neoadjuvant, adjuvant, and salvage chemotherapy, contributing to heterogeneity that may limit the generalizability of the findings. Sixth, the study focused on AEs and treatment completion rates without a comprehensive evaluation of other clinical outcomes. Future prospective studies with larger and more homogeneous cohorts are warranted to further validate these findings and explore the utility of GA in various treatment settings.

Conclusion

The pretreatment G8 score was significantly associated with the treatment completion rate of dd-MVAC therapy, underscoring its value as a predictive tool for the management of older patients with urothelial carcinoma.

Abbreviations

dd-MVAC, dose-dense methrotrexate vinblastine doxorubicin and cisplatin;

G8, Geriatric 8;

GA, geriatric assessment;

AE, adverse event;

CTCAE, Common Terminology Criteria for Adverse Events;

ECOG PS, Eastern Cooperative Oncology Group Performance Status;

BMI, body mass index;

CGA, comprehensive geriatric assessment

Conflicts of interest

The authors declare no conflict of interest.

Funding

This study did not receive any funding/grant support for this study.