Prognostic utility of MRI features in intradiverticular bladder tumor

Abstract

Background:

Intradiverticular bladder tumors (IDBT) are rare but clinically important, as they are difficult to assess endoscopically due to limited anatomic access and risk of perforation. MRI may be helpful in assessing IDBT and providing relevant staging and prognostic information.

Purpose:

To assess MRI findings of IDBT and their relationship with overall survival.

Methods:

This retrospective study included 31 consecutive patients with IDBT undergoing MRI from 2008–2018 identified through electronic medical records and PACS database search. Two radiologists independently assessed the following MRI features: size (>3 vs ≤3 cm), diverticular neck involvement, Vesical Imaging-Reporting and Data System (VI-RADS) score (>3 vs ≤3), perivesical fat infiltration, additional tumors and suspicious pelvic lymph nodes. Overall survival was estimated using Kaplan–Meier analysis; and the relationship with clinicopathological and MRI features was determined using the Cox proportional-hazards regression model. Inter-reader agreement was assessed using intra-class correlation coefficients (ICC) and Cohen’s kappa (K).

Results:

Median follow-up was 1044 days (IQR, 474–1952 days). Twenty-six (83.9%) patients underwent surgical treatment with or without neoadjuvant chemotherapy. On MRI, greater tumor size (>3cm), diverticular neck involvement, perivesical extension, and suspicious lymph nodes were associated with lower overall survival (HR = 3.6–8.1 and 4.3–6.3 for the two radiologists, p ≤0.03). Other clinicopathological or MRI findings were not associated with survival (p = 0.27–0.65). Inter-reader agreement was excellent for tumor size (ICC = 0.991; 95% CI 0.982–0.996), fair for VI-RADS (K = 0.52, 95% CI, 0.22–0.82), and moderate for others (K = 0.61–0.79).

Conclusion:

In patients with IDBT, several MRI features were significantly associated with overall survival. Utilizing all available clinicopathological and imaging information may improve estimation of prognosis.

Introduction

Intradiverticular bladder tumors (IDBT) are rare, accounting for approximately 1–10% of all bladder cancers [1]. Bladder diverticula are considered at increased risk of developing tumor compared with the rest of the bladder as they are (1) lined with urothelial tissue and (2) prone to urinary stasis which may be associated with chronic inflammation or infection and longer exposure to carcinogens [2; 3]. Although the literature on IDBTs is scarce due to their rarity, it is recognized that a few special clinical aspects of IDBT require attention regarding diagnosis and prognosis when compared with bladder cancer in general. First, visualization and obtaining adequate tissue for staging from the IDBT through transurethral resection (TUR) may be difficult as the cystoscope must pass through the diverticular neck. This may be especially problematic for diverticula with substantially narrow necks which may mask the presence of IDBT or with acute angle of entry limiting passage of the scope [4]. Second, the risk of perforation from TUR is higher due to the thin diverticular bladder wall with paucity or absence of the muscularis propria layer — resulting in potential limitation for deep resections, which can underestimate the stage of IDBT [4–6]. Third, since diverticula lack a distinct muscular backing, progression to perivesical fat invasion (stage T3 disease) may be more likely and in turn result in poorer survival [1; 2; 7].

Cross-sectional imaging such as computed tomography (CT) or magnetic resonance imaging (MRI) are important adjunctive modalities to assist with clinical staging. With the exception of one prior study by Di Paolo et al [8] which assessed the value of CT for IDBT in 34 patients, most of the literature related to imaging of IDBT are case reports and small case series with only a few patients, most of these only assessing CT but not MRI [9–14]. MRI can be of additional value considering its better soft tissue resolution, allowing for enhanced assessment of local disease extent and detection of nodal metastases which are known in pathological specimens to affect prognosis in bladder tumors in general [15–17]. Therefore, the objective of this study was to assess the MRI findings of IDBT and evaluate their relationship with overall survival.

Material and methods

Patients

This study was compliant with the Health Insurance Portability and Accountability Act and received approval from our institutional review board who waived need for informed consent considering the retrospective nature of the study. We searched our institutional PACS database and electronic medical records for patients who met the following inclusion criteria: (i) diagnosed with IDBT by TUR or cystectomy between April 2008 and December 2018 and (2) had undergone MRI at the time of TUR. Details of the search query for the electronic databases are provided in the Electronic Supplementary Material 1, Among 33 patients identified, we excluded 2 patients lost to follow-up without further diagnostic work-up or treatment. No patients were excluded due to poor image quality. When patients had multiple MRI scans, we used the earliest available one for the purpose of analysis. Our final patient population consisted of 31 patients.

MRI acquisition

MRI examinations were performed on 1.5- (Optima MR450w, Signa HDxt, and Signa Excite, GE Healthcare) and 3.0-Tesla scanners (Discovery MR750, Discovery MR750w, and Signa PET/MR, GE Healthcare) with multichannel phased-array coils. There was variability in the MRI acquisition technique over the long study duration for patient inclusion, however, the bladder MRI was obtained in general according to the following methods. All patients voided upon check in and were instructed to drink 8 oz of water. Scout images were checked to ensure adequate distension of the bladder, for which additional intravenous fluids were administered when under-distended. Intravenous glucagon was administered to decrease bowel peristalsis. The multiparametric sequences included (1) axial large field-of-view (FOV) unenhanced T1-weighted images (T1WI), (2) small FOV T2-weighted images (T2WI) in 3 orthogonal planes, (3) axial and sagittal diffusion-weighted images, (4) multiphase contrast-enhanced images were obtained in the sagittal plane at 0, 30, 60, and 120 seconds after contrast injection and additionally at 5 minutes in the axial or coronal planes. Details of acquisition parameters are provided in Table 1.

Table 1.

Bladder MRI protocol

Sequence Parameter╲	Large FOV unenhanced T1WI	Multiplanar T2WI	Diffusion-weighted images	Multi-phase contrast-enhanced T1WI
Plane	A	A, C, S	A, S	S & C or A
FOV (cm)	28–36	20–24	20–24	20–24
Slice thickness/gap	5–7/1	4/1–2	4/0–1	4/−2 or 3/−1.5
TR/TE *	500–800/7–10 400–650/8–10	3500/102 3500–4000/102	6000/60–66 3500–6000/6 –96	3.9–5.3/1.9–2.1 3.6–4.5/1.4–2.1
Flip angle	90	90	90	15
NEX	2	3	6	1
Matrix	448 × 224	320 × 224	128 × 128	256 × 128–160 320 × 192†
Coverage	Iliac Crest to Pubic Symphysis	Bladder	Bladder	Bladder / Kidney to bladder ‡
Others			b-value = 0, 400, 700 §	0, 30, 60, 120 sec, and 5 min after contrast ¶

A = axial; C = coronal; FOV = field-of-view; NEX = number of excitations; S = sagittal; TE = echo time; TR = repetition time; T1WI = T1-weighted imaging; T2WI = T2-weighted imaging

^*upper values used for 3-Tesla and lower values used for 1.5-Tesla scanners

^†upper values for axial and sagittal planes; lower values for coronal plane

^‡Bladder-focused for sagittal and coronal planes; from kidney to bladder for coronal planes

^§0, 400 for sagittal and 0, 700 for axial planes. Of note, DWI was not performed in 22.6% (7/31) of the patients.

^¶0, 30, 60, and 120 sec for sagittal and 0, 5 min for coronal

MRI interpretation

Two radiologists (R1, S. W. and R2, S. G.) with 4 and 2 years of post-residency experience, respectively, specializing in genitourinary oncologic imaging independently reviewed the MRIs, retrospectively. Although the radiologists were aware that these patients had IDBT, they were blinded to all other clinicopathological information including staging and survival data. The following MRI findings were assessed: (1) Maximal size of the IDBT (measured on any plane), and additionally dichotomized as large (>3 cm) vs small (≤3 cm) for further analysis [18; 19]; (2) involvement of diverticular neck; (3) muscle-invasiveness in the intradiverticular component based on Vesical Imaging-Reporting and Data System (VI-RADS) with a score of >3 considered positive [16; 20]; (4) perivesical fat infiltration, when an irregular outer border with streaky areas of signal intensity similar to the tumor was seen in the adjacent perivesical fat [21; 22]; (5) presence of additional tumors; and (6) pelvic lymph nodes suspicious for metastases, defined as those with short axis diameter >1 cm or >0.6 cm when rounded or irregular-shaped [23; 24].

Clinicopathological and survival data

The following information was obtained from the electronic medical records: age, gender, TUR tumor grade and stage based on the third edition of the World Health Organization histological classification of tumors of the urinary tract [25], pathological tumor stage on cystectomy specimen according to the 7^th edition of American Joint Committee on Cancer TNM staging system [26], and type of treatments received.

Statistical analysis

Medians and their interquartile ranges (IQR) for continuous variables and frequencies and their percentages for categorical variables were used to summarize the patient and tumor characteristics. Inter-reader agreement for continuous variables was evaluated using the intra-class correlation coefficients (ICC) with the following criteria for the degree of agreement: ICC = 0.0–0.39, poor; 0.40–0.59, fair; 0.60–0.74, good; and 0.75–1.00, excellent [27]. For categorical variables, the Cohen’s Kappa (K) was used with the following criteria: K = 0.0–0.20, poor; 0.21–0.40, fair; 0.41–0.60, moderate; 0.61–0.80, good; 0.81–1.00, very good [28]. Overall survival, defined as the time from MRI to death from any cause, was estimated using Kaplan–Meier analysis. The Cox proportional-hazards regression model was used to determine the relationship between MRI findings and clinicopathological variables with overall survival. Hazard ratios (HR) and their 95% confidence intervals (CI) were obtained and the log-rank test was used to test for statistical significance. For analyses that included zero events, Firth’s penalized likelihood estimation was used [29]. Only univariate analysis was planned due to the small number of patients. We used R (version 3.6.1; R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 18; SPSS, Chicago, Ill) for statistical analysis. P values <0.05 were considered statistically significant.

Results

Patient and tumor characteristics

The characteristics of the patients and IDBTs are shown in Table 2. All but two patients were men, the median age was 68 (IQR, 60–76). The histological subtypes of the IDBTs were urothelial carcinomas without any variant histology (n = 13), urothelial with squamous differentiation (n = 8), urothelial with other variants (n = 9) and small cell tumor (n = 1). At TUR, most IDBTs were high grade (n = 30 [96.8%]) and invasive (n = 28 [90.3%]). Twenty-six (83.9%) of the patients underwent surgical treatment with or without neoadjuvant chemotherapy (n = 13 for each), including radical cystectomy (n = 16), partial cystectomy (n = 8), and diverticulectomy (n = 2). In these patients, the final pathological specimens showed perivesical fat invasion (stage pT3) in 42.3% (11/26); no tumors were staged as pT2. There was downstaging from TUR to final pathology in 42.3% (11/26) patients. Five patients did not undergo surgical treatment, all of whom had suspicion of perivesical fat invasion on MRI and were treated with chemotherapy and radiation (n = 2), chemotherapy (n = 2) or TUR alone (n = 1). The median follow-up after MRI for was 1044 days (IQR, 474–1952 days). The median interval between MRI and TUR and between MRI and surgery were 28 days (IQR, 17–38 days) and 83 days (IQR, 29–146 days), respectively.

Table 2.

Characteristics of the patients and tumors

Clinicopathological variable			Number (percentage)*
Age (years)			68 (60–76)
Gender	Male		29 (93.5)
	Female		2 (6.5)
Histological subtype	Urothelial	Not otherwise specified	13 (41.9)
		Squamous differentiation	8 (25.8)
		Glandular differentiation	4 (12.9)
		Sarcomatoid features	2 (6.5)
		Micropapillary pattern	1 (3.2)
		Abundant myxoid stroma	1 (3.2)
		Clear cell morphology	1 (3.2)
	Small cell tumor †		1 (3.2)
Tumor grade	High grade		29 (93.5)
	Low grade		2 (6.5)
Staging on TUR	Invasive (T1)		28 (90.3)
	Non-invasive (<T1)		3 (9.7)
Staging on surgical specimen ‡	T0		4 (12.9)
	Tis		4 (12.9)
	Ta		2 (6.5)
	T1		5 (16.1)
	T3		11 (35.4)
Treatment	Surgery without neoadjuvant chemotherapy		13 (41.9)
	Surgery after neoadjuvant chemotherapy		13 (41.9)
	Chemotherapy + palliative radiation treatment §		2 (6.5)
	Chemotherapy ||		2 (6.5)
	TUR only ¶		1 (3.2)
Time between MRI and last follow-up (days)			1044 (474–1952)
Time between MRI and TUR (days)			28 (17–38) #
Time between MRI and surgery (days)			83 (29–146)

^*data are number of patients with percentages in parentheses except for continuous variables which are presented in medians with interquartile ranges (IQR) in parentheses

^†small component of urothelial component

^‡data for 26 patients that underwent surgical treatment

^§Progressed after (neo)adjuvant chemotherapy and therefore forwent surgical treatment and received palliative radiation treatment

^||Palliative chemotherapy due to adjacent organ invasion or non-regional node metastasis

^¶TUR only due to underlying medical condition

^#11 days (IQR 7–22) and 31 days (IQR 18–38) for patients with MRI followed by TUR (n = 6) and TUR followed by MRI (n = 25), respectively.

MRI findings and inter-reader agreement

Median tumor sizes were 3.1 cm (IQR, 1.2–5.9) and 3.0 cm (IQR 1.7–5.9) for R1 and R2. Diverticular neck involvement was present in 15 (48.4%) patients according to both readers. Muscle-invasive disease based on VI-RADS was suspected in 18 (58.1%) and 21 (67.7%) patients for R1 and R2 (Electronic Supplementary Material 2). Perivesical fat invasion was noted in 15 (48.4%) patients by both readers. Additional tumors were detected in 3 (9.7%) and 2 (6.5%) patients. Suspicious lymph nodes were identified in 12 (38.7%) and 9 (29.0%) patients. Inter-reader agreement was excellent for tumor size (ICC = 0.991; 95% CI 0.982–0.996), fair for muscle-invasive disease (K = 0.52, 95% CI, 0.22–0.82), and moderate for the remaining MRI findings (K = 0.74, 0.61, 0.78, and 0.79 for neck involvement, perivesical invasion, presence of additional tumors, and suspicious pelvic lymph nodes). Representative cases demonstrating these MRI features are presented in Figures 1 and 2.

Figure 1. 77-year-old man with intradiverticular bladder tumor.

A. Axial T2-weighted image shows large mass (*) filling left posterolateral diverticulum demonstrating restricted diffusion on diffusion-weighted imaging (B) and apparent diffusion coefficient map (C). Largest diameter measures 6.0 and 6.6 cm by radiologists 1 and 2. Both radiologists scored this mass as VI-RADS 5 lesion with diverticular neck involvement (arrow), perivesical fat invasion (arrowheads), and suspicious a left obturator lymph node (circle). Transurethral resection showed high grade urothelial carcinoma with sarcomatoid differentiation and extensive necrosis invading lamina propria. Radical cystectomy after neoadjuvant chemotherapy revealed perivesical fat invasion. Patient died at approximately 1 year (381 days) of follow-up.

Figure 2. 72-year-old man with intradiverticular bladder tumor.

A. Axial T2-weighted image shows small mass (*) filling left posterolateral diverticulum demonstrating restricted diffusion on diffusion-weighted imaging (B) and apparent diffusion coefficient map (C). Sagittal T2-weighted image (D) and dynamic contrast-enhanced image (E) show thin preserved layer of diverticular wall (arrows). Also note multiple diverticula without tumors (arrowheads). Radiologist 1 measured 2.2 cm and gave VI-RADS score of 3. Radiologist 2 measured 1.7 cm and gave VI-RADS score of 4. Both radiologists did not identify diverticular neck involvement, perivesical fat invasion, or suspicious lymph nodes. Transurethral resection showed high grade non-invasive papillary urothelial carcinoma. Radical cystectomy revealed only lamina propria invasion. Patient was alive at approximately 5 years (1952 days) after MRI.

Overall survival

Kaplan-Meier survival curves for overall survival stratified to MRI findings and clinicopathological findings are shown in Figures 3–5, respectively, with their corresponding hazard ratios in Tables 3 and 4. Among MRI findings, greater tumor size (>3cm), involvement of diverticular neck, perivesical extension on MRI, and suspicious lymph nodes were associated with poor overall survival (HR = 3.6–8.1 and 4.3–6.3 for R1 and R2, respectively, p ≤0.03). The presence of additional tumors or suspicion of high VI-RADS scores were not associated with survival (p = 0.28–0.98). Type of treatment was significantly associated with survival: nonsurgical treatment was associated with poorer survival compared with surgery without neoadjuvant treatment (HR = 163.1, 95% CI 9.4–2842.7, p <0.01). Patients who underwent surgery after neoadjuvant treatment showed lower survival rates than those that did not receive neoadjuvant treatment, however without statistical significance (HR = 5.9, 95% CI 0.7–50.9). Other clinicopathological variables were not associated with survival (p = 0.27–0.65).

Figure 3.

Kaplan-Meier curves showing relationship between MRI findings and overall survival by Reader 1.

Figure 5.

Kaplan-Meier curves showing relationship between MRI findings and overall survival by Reader 2.

Table 3.

Relationship between MRI findings of Intradiverticular bladder tumors and overall survival according to interpretations by two Radiologists (R1 and R2).

MRI finding	Category	Radiologist 1		Radiologist 2
		Hazard ratio (95% CI)	p-value*	Hazard ratio (95% CI)	p-value*
Size	>3cm	6.3 (1.4–29.6)	0.01	6.3 (1.4–29.6)	0.01
	≤3cm	1		1
Size	Continuous (cm)	1.2 (1.0–1.6)	0.09	1.2 (1.0–1.6)	0.09
Diverticular neck	Involved	5.2 (1.3–20.1)	0.01	4.3 (1.1–16.3)	0.02
	Not involved	1
VI-RADS score	>3	1.8 (0.5–6.2)	0.34	2.0 (0.5–7.8)	0.28
	≤3	1
Perivesical fat invasion	Present	3.6 (1.0–12.5)	0.03	4.7 (1.2–17.9)	0.01
	Absent	1
Additional tumors	Present	1.0 (0.1–8.1)	0.98	1.8 (0.2–13.9)	0.59
	Absent	1
Suspicious lymph nodes	Present	8.1 (2.1–31.5)	<0.01	5.3 (1.6–18.1)	<0.01
	Absent	1

VI-RADS = Vesical Imaging-Reporting and Data System

^*p-values based on log-rank test

Table 4.

Relationship between clinicopathological variables and overall survival.

Clinicopathological variable	Category	Hazard ratio (95% CI)	p-value
Age (years)	≥70	1.4 (0.4–4.7)	0.57
	<70	1
Gender	Male	0.3 (0.0–2.9)	0.28
	Female	1
Histologic subtype	Any variant	1.3 (0.4–4.6)	0.65
	Urothelial NOS	1
Histologic subtype	Squamous variant	1.6 (0.4–6.4)	0.49
	Others	1
Staging on TUR	Invasive (≥T1)	3.6 (0.5–467.3)	0.27*
	Non-invasive(<T1)	1
Staging on surgical specimens	≥T3	2.1 (0.4–10.4)	0.36
	≤T1	1
Type of treatment	Nonsurgical treatment	163.1 (9.4–2842.7)	<0.01
	Surgery after neoadjuvant	5.9 (0.7–50.9)
	Surgery without neoadjuvant	1

^*Firth’s penalized likelihood method used due to absence of event (death) in one group. All other p-values are based on log-rank test.

Discussion

In this study, we assessed the MRI findings of IDBT and their relationship with overall survival in 31 patients. With a relatively larger number of patients having this rare type of bladder tumor that have undergone MRI compared with prior studies [9; 11], we were able to find that several MRI findings (e.g., size >3 cm, diverticular neck involvement, perivesical fat invasion, and lymph nodes with suspicious MRI features [short axis diameter >1 cm or >0.6 cm with rounded or irregular shape]) were significantly associated with overall survival. Given the recent increase in recognition of the utility of MRI for evaluation local extent of bladder tumors in general [15; 16; 20] and the potential limitations of cystoscopic evaluation for IDBTs (eg, technical difficulties and accessibility related to narrow diverticular neck and increased risk of perforation from thin wall) [4–6], we hypothesize that MRI may provide additional staging and prognostic information in the IDBT setting.

Among several MRI findings, larger tumor size, diverticular neck involvement, and perivesical fat invasion were significantly associated with poorer overall survival. These MRI findings are generally indicative of greater local extent of the IDBT and thus their relationship with survival can be intuitively understood as well as in agreement with the literature [7; 30]. The relationship between larger size on MRI and survival is in agreement with a previous study by Di Paolo et al [8] in which the size of the IDBT on CT was also associated with poorer survival. However, in their study, involvement of the diverticular neck was not associated with survival. This may be due to the fact that MRI has substantially better soft tissue resolution than CT enabling more accurate delineation of the tumor and its relationship with the normal bladder wall and the diverticular neck [31]. Furthermore, this has clinical implications as the presence or absence of diverticular neck involvement is a critical component to operative planning when considering bladder-conserving techniques such as diverticulectomy or partial cystectomy in order to minimize the risk of a positive surgical margin.

Perivesical fat invasion, or T3 disease, was associated with poorer survival when suggested by MRI but not when identified on final pathological specimens. This may be attributed to some of the following reasons. First, the final pathological stage was not available in 5 patients who did not undergo surgical treatment. The small sample size in this group may have insufficient power to show statistically significant difference. Second, neoadjuvant chemotherapy was undertaken in approximately half (12/26 [46.2%]) of the patients who received surgery. In most of these patients (10/12 [83.3%]), chemotherapy was initiated after MRI, which may have resulted in discrepancy between MRI and final pathology. In a prior randomized controlled trial assessing the effects of neoadjuvant chemotherapy in (non-diverticular) bladder tumors [32], radiological response (hazard ratio = 4.1; 95% CI, 1.3–12.5; P = 0.01) showed a greater ability to predict disease-free survival when compared with pathological response (hazard ratio = 2.6; 95% CI, 0.8–8.1; P = 0.08). Third, MRI is unable to detect “microscopic” perivesical fat invasion (T3a) and therefore is primarily utilized to assess “macroscopic” perivesical spread (T3b) [33]. A previous study by Neuzillet et al [34] showed that the oncological outcomes of pT2b and pT3a were similar while only patients with pT3b were significantly worse. In line with this, the sensitivity (81.8%) was moderate compared with the high specificity (93.3%) of MRI for determining perivesical invasion, in the 26 patients that underwent surgical management. Taking all the above into consideration, although the heterogeneity in treatment and paucity of surgical patients may have hindered the interpretation of the results, perivesical spread as indicated by MRI should be factored in together with the pathological results for optimal prognostic estimation. Additionally, given the association with higher stage and decreased survival, MRI findings of perivesical fat invasion may also be used to select patients for neoadjuvant chemotherapy prior to surgery.

In our study, there were no patients with pT2 stage (muscle-invasive disease) on the surgical specimens. This is in agreement with the fact that acquired bladder diverticula lack the muscularis propria layer and thus the recently updated AJCC Staging Manual 8th edition formally recommends excluding “pT2” stage for IDBT [1; 35; 36]. It may also explain why VI-RADS scoring system was not associated with survival in IDBTs in this study. In contrast to the increasing acceptance and reports of high diagnostic performance of this novel MRI scoring system which was primary aimed at predicting muscle-invasive disease [16; 20], it may be unsuitable for IDBTs.

The presence of suspicious nodes on MRI were also associated with poorer survival. Node positive status is one of the most important factors related to overall and cancer-specific survival in patients with bladder cancer [37; 38]. MRI has been tested rigorously for this purpose exhibiting excellent specificity but poor and heterogeneous sensitivity for detecting metastatic nodes in patients with bladder cancer [17]. Especially, since assessment of lymph nodes on MRI are mainly based on size criteria and morphology (e.g., irregular shape, necrosis, etc.), there is inherent limitation in detecting micrometastasis, and thus resulting in poor sensitivity.

The known difficulties in clinical and pathological assessment of IDBTs are highlighted in this study. For example, the TUR stage was not associated with survival. This may reflect understaging, a well-known issue in bladder cancer in general which is even more accentuated in IDBTs given its additional limitations of difficult approach by cystoscope and hesitancy for deep resections due to the thin diverticular wall. Furthermore, several other clinicopathological variables that are known to have prognostic significance including advanced age (≥70 years), gender, and histological subtype were not associated with survival [37; 39]. However, it is noteworthy that treatment decisions were significantly associated with survival. Patients who did not receive surgical management demonstrated inferior survival compared with those who underwent surgical treatment without neoadjuvant treatment. The decision to forego surgical management was based on multiple clinical parameters, including tumor extent and stage, collectively based on clinical and imaging characteristics (e.g., invasive disease on TUR (5/5), perivesical fat invasion on MRI (5/5), suspicious nodes on MRI (3/5), age >70 years (4/5), and response evaluation after chemotherapy (progression in 2/5)). Selection bias was likely the driver of outcomes as opposed to particular treatment type. This again emphasizes the fact that all available clinicopathological and imaging information should be used for better estimation of prognosis in patients with IDBT.

There were multiple limitations in this study. Although, this is the largest study to date that addresses MRI and IDBT, the sample size was too small (N = 31) to allow multivariable analyses. Second, inherent biases may be present due to retrospective design and heterogeneity in the clinical setting, MRI protocols, and management. For instance, MRI was performed after TUR in a large proportion of the patients. This could have altered the MRI findings as it is known that post-TUR changes can mask or exaggerate extent of tumor [40]. MRI protocols have changed over time and remote examinations did not include advanced MRI sequences such as diffusion-weighted imaging which are known to be helpful in determining local disease extent [22; 33]. For these patients there is limitation in strictly applying the VI-RADS scores and further studies are warranted to evaluate the usage of abbreviated or biparametric MRI protocols. The heterogeneity in management of patients could have altered the interpretation of survival analysis. Neoadjuvant chemotherapy was used in a significant proportion of patients (42%), which could have affected pathologic and oncologic outcomes. In addition, in the minority of patients that received neoadjuvant treatment before MRI (2/10 in the surgically managed patients), this may have affected interpretation of MRI (e.g., VI-RADS scores, perivesical invasion, etc). Although recent trials such as the PURE-01 study show promising results for usage of multiparametric MRI after neoadjuvant treatment, validation is need, especially with regards to application of VI-RADS [41]. Nevertheless, in order to account for the rarity of this entity, inclusion of all potential patients with IDBT was required to maximize number of patients.

Conclusion

In patients with IDBT, MRI findings of larger size, perivesical fat invasion, diverticular neck involvement and suspicious lymph nodes were significantly associated with overall survival. Taking into account all available clinicopathological and imaging information may improve estimation of prognosis.

Figure 4.

Kaplan-Meier curves showing relationship between clinicopathological findings and overall survival.

Abbreviations:

CT

computed tomography

FOV

field of view

HR

hazard ratio

ICC

intra-class correlation

IDBT

intradiverticular bladder tumor

MRI

magnetic resonance imaging

TUR

transurethral resection

T1WI

T1-weighted image

T2WI

T2-weighted image

VI-RADS

Vesical Imaging-Reporting and Data System