Context

The pathologic diagnosis of pT1 substage in conventional transurethral resection of bladder tumor specimens is inaccurate and has low interobserver reproducibility owing to fragmentation and cauterization of the specimens. En bloc resection of bladder tumor is a novel surgical procedure that improves diagnostic feasibility and accuracy in the pathologic diagnosis of bladder cancer, including depth and extent of invasion.

Objective

To examine the prognostic value of multiple pT1 subclassification methods, using only en bloc resection specimens.

Design

We examined 106 patients with T1 bladder cancer who underwent en bloc resection. The pT1 substages were assigned by 3 different subclassification methods by using the muscularis mucosae or stalk of the papillary lesion as diagnostic landmarks or millimetric depth of invasion. Intergroup differences in progression-free survival and recurrence-free survival rates were analyzed. The prognostic values of clinicopathologic factors for progression/recurrence were analyzed by using multivariate analysis.

Results

The pT1 substage was evaluable in all cases. Tumors with invasion into/beyond the muscularis mucosae and those beyond the stalk of the papillary lesion were associated with worse progression-free survival (P = .002 and P = .01, respectively). Notably, no patient with invasion confined to the stalk had disease progression during the 23-month median follow-up period. Only the pT1 subclassification method using the muscularis mucosae was an independent prognosticator of progression in multivariate analysis (P = .03).

Conclusions

Precise pathologic subclassification of invasion using en bloc resection specimens may enable accurate prognosis and assessment in patients with bladder cancer with suspicious shallow invasion.

Non–muscle-invasive bladder cancer (BCa), including T1 cancer, comprises 70% to 80% of untreated BCas. Among the non–muscle-invasive BCas, T1 BCa comprises a relatively large proportion, from 20% to 25%.13  T1 BCa includes cases with varied clinical outcomes, and patients in a better prognosis group may be followed up only by observation after focal treatment, including transurethral resection of bladder tumor (TURBT). In contrast, patients in a worse prognosis group have rapid progression to T2 or above and require immediate additional treatment. Appropriate prognostic markers to define these groups have not been determined.

Several pT1 subclassification methods have been recently proposed, and their prognostic values have been examined in conventional TURBT (cTURBT) specimens.49  The most widely reported method uses the muscularis mucosae (MM) as a diagnostic landmark (MM method); specifically, pT1 BCa cases with invasion into a layer shallower than the MM are classified as pT1a, while those involving invasion into or beyond the MM are classified as pT1b (Figure 1, A through D).6  Another method uses the depth of invasion (DOI) from the epithelial basement membrane as a diagnostic measure (DOI method). In the DOI method, cases with a single invasion focus of DOI of 0.5 mm or less are classified as microinvasions (pT1m), while all other cases are classified as extensive invasions (pT1e) (Figure 2, A through D).7  Another less-reported method uses the stalk of the papillary lesion (PS) as a diagnostic landmark (PS method); specifically, cases with invasion confined to the stroma of the PS are classified as pT1-cpap, while those with invasion beyond the base of the PS are labeled as pT1-bpap (Figure 3, A through D).8 

Figure 1

Schematic (A and C) and representative hematoxylin-eosin–stained histologic images (B and D) of each pT1 substage, using the muscularis mucosae (MM) method. The images in the top row (A and B) represent pT1a, while those in the bottom row (C and D) represent pT1b. In the schematic pictures, red dots show the distribution of invasive cancer cells, solid red lines outline papillary tumors, solid black lines show the mucosal surface, yellow bands represent the MM, and blue ovals show the vascular plexus. In the histologic images, black broken lines show the deepest front or distribution of invasive lesions, black arrows point to the MM, and white arrows indicate the vascular plexus (original magnification ×40 [B and D]).

Figure 1

Schematic (A and C) and representative hematoxylin-eosin–stained histologic images (B and D) of each pT1 substage, using the muscularis mucosae (MM) method. The images in the top row (A and B) represent pT1a, while those in the bottom row (C and D) represent pT1b. In the schematic pictures, red dots show the distribution of invasive cancer cells, solid red lines outline papillary tumors, solid black lines show the mucosal surface, yellow bands represent the MM, and blue ovals show the vascular plexus. In the histologic images, black broken lines show the deepest front or distribution of invasive lesions, black arrows point to the MM, and white arrows indicate the vascular plexus (original magnification ×40 [B and D]).

Close modal
Figure 2

Schematic (A and C) and representative hematoxylin-eosin–stained histologic images (B and D) of each pT1 substage, using depth of invasion method; pT1m is represented in the images in the top row (A and B), and pT1e is represented in the images in the bottom row (C and D). In addition to the descriptions provided in the Figure 1 legend, the black bidirectional arrows in the histologic images indicate the depth of invasion (original magnification ×200 [B and D]).

Figure 2

Schematic (A and C) and representative hematoxylin-eosin–stained histologic images (B and D) of each pT1 substage, using depth of invasion method; pT1m is represented in the images in the top row (A and B), and pT1e is represented in the images in the bottom row (C and D). In addition to the descriptions provided in the Figure 1 legend, the black bidirectional arrows in the histologic images indicate the depth of invasion (original magnification ×200 [B and D]).

Close modal
Figure 3

Schematic (A and C) and representative hematoxylin-eosin–stained histologic images (B and D) of each pT1 substage, using the papillary stalk method. The images in the top row (A and B) represent pT1-cpap, while the images in the bottom row (C and D) represent pT1-bpap. In addition to the descriptions provided in the Figure 1 legend, broken blue lines show the bases of papillary lesions (original magnification ×40 [B and D]).

Figure 3

Schematic (A and C) and representative hematoxylin-eosin–stained histologic images (B and D) of each pT1 substage, using the papillary stalk method. The images in the top row (A and B) represent pT1-cpap, while the images in the bottom row (C and D) represent pT1-bpap. In addition to the descriptions provided in the Figure 1 legend, broken blue lines show the bases of papillary lesions (original magnification ×40 [B and D]).

Close modal

Several pathology guidelines, including the AJCC Cancer Staging Manual (8th edition10) and the latest World Health Organization classification (5th edition11), recommend reporting the pT1 subclassification.12  However, major clinical guidelines do not adopt the pT1 subclassification as a decision-making factor3,13  owing to its low interobserver reproducibility and diagnostic accuracy, particularly when obtained with the MM method.9,1416  Detection of anatomic structures in the bladder wall and the invasion focus is often problematic in the pathologic examination of cTURBT specimens owing to fragmentation and cauterization of the specimens, leading to difficulty in determining the pT1 subclassification.

En bloc resection of bladder tumor (ERBT) is a relatively new surgical technique in which BCa is resected en bloc with the surrounding bladder wall tissue (Figure 4), resulting in less cauterization and fragmentation. Therefore, the anatomic structure of the bladder wall is easily confirmed by pathologic examination,17  leading to better pathologic evaluability.18  A previous study showed that the interobserver reproducibility rate of the pT1 subclassification, using the MM method, was higher in ERBT specimens than in cTURBT specimens.16  Furthermore, the MM method was a prognosticator of disease progression in T1 BCa in a single-institute cohort where one-fourth of patients underwent ERBT.19  However, ERBT cases were not analyzed separately from cTURBT cases in that study owing to the small number (32) of ERBT cases. In addition, the study did not analyze the PS method.

Figure 4

A representative macroscopic image of en bloc resection of bladder tumor specimens.

Figure 4

A representative macroscopic image of en bloc resection of bladder tumor specimens.

Close modal

With a multi-institutional design, we examined the predictive value of 3 different pT1 subclassification methods in a large ERBT cohort.

Patients

This was a multi-institutional retrospective study. A total of 106 patients with T1 BCa who underwent ERBT at Jikei University Kashiwa Hospital (Tokyo, Japan) (n = 55), Ureshino Medical Center (Saga, Japan) (n = 38), or Saitama Medical Center (Saitama, Japan) (n = 13) between April 2013 and March 2021 were included. Hematoxylin-eosin–stained specimens from all patients were reviewed and diagnosed as pT1 by a genitourinary pathologist. Patients with subsequent early radical cystectomy or cancer at the vesicoureteral junction were excluded. ERBT was performed by using a bipolar TURis system (Olympus Medical Systems, Tokyo, Japan) with a needle or loop-type electrode, as previously reported.20  Patients were followed up as previously reported.20  The application of repeated TURBT (reTUR) and immediate single bladder instillation and/or bacillus Calmette-Guérin instillation therapy depended on institutional guidelines or the physician's preference.20 

Pathologic Evaluation

The ERBT specimens were step-sectioned at 2- to 3-mm intervals and totally embedded. All cases were reviewed by a genitourinary pathologist, and pT1 substages were assigned by using 3 different methods: MM (Figure 1, A through D), DOI (Figure 2, A through D), and PS (Figure 3, A through D), as described above.68  In cases without detectable MM, the vascular plexus associated with the MM21  was substituted for the MM.

Outcome Measures and Statistical Analysis

Our primary and secondary outcome measures were progression and recurrence, respectively. Progression was defined as an advancement in the pathologic stage to pT2 or above, identification of lymph node/distant metastasis, or death due to BCa. Recurrence was defined as the reappearance of pathologically confirmed urothelial carcinoma in the bladder after reTUR in patients with reTUR and after the initial ERBT in those without reTUR.

Progression-free survival (PFS) and recurrence-free survival (RFS) rates were estimated with the Kaplan-Meier method, and intergroup differences were compared by using the log-rank test in each pT1 subclassification method. Hazard ratios (HRs) of pT1 subclassification methods and other clinicopathologic variables for progression/recurrence were calculated by using univariate and multivariate Cox proportional hazard regression analyses. Only variables with P < .20 by univariate analysis were included in the multivariate analysis. Statistical significance was set at P < .05 for all analyses. The EZR software package based on R (R Foundation for Statistical Computing, Vienna, Austria) was used for analyses.22 

Research Ethics

This study was approved by the ethics committee of the affiliated institutions and was performed in accordance with the Declaration of Helsinki. Informed consent was not required owing to the retrospective study design.

Patient Characteristics and Pathologic Findings

Patient characteristics are shown in Table 1. Among the 106 patients, 12 (11.3%) had a previous upper urinary tract urothelial carcinoma history, and 16 (15.1%) had recurrent tumors. The median tumor size was 20 mm, with only 10 cases (9.4%) exceeding 30 mm. The MM-vascular plexus was detected by pathologic examination in all cases. The muscularis propria was detected in 99 cases (93.4%). Urothelial carcinoma in situ was present in 37 cases (34.9%). In addition to the invasive component, a noninvasive papillary lesion was present in 105 cases (99.1%), and 1 had only carcinoma in situ lacking a papillary lesion. Variant histology was present in 10 cases (9.4%), of which 7 showed divergent differentiation (4 glandular and 3 squamous differentiation), with the rest showing only 1 of the micropapillary, lymphoepithelioma-like, or poorly differentiated (osteoclast-like giant cell) subtypes in each case. The pT1 substages using the 3 different methods were evaluable in all cases. The distributions of the pT1 substages were as follows: 74 cases (69.8%) of pT1a and 32 cases (30.2%) of pT1b, using the MM method; 22 cases (20.8%) of pT1m and 84 cases (79.2%) of pT1e, using the DOI method; and 33 cases (31.1%) of pT1-cpap and 73 cases (68.9%) of pT1-bpap, using the PS method.

Table 1

Clinicopathologic Characteristics and Follow-Up Data

Clinicopathologic Characteristics and Follow-Up Data
Clinicopathologic Characteristics and Follow-Up Data

Progression-Free Survival and pT1 Subclassification

Disease progression occurred in 13 of the 106 patients (12.3%) during the 23-month median follow-up period, with an estimated 3-year PFS rate of 81.7% (Table 1). The 3-year PFS rate was significantly lower in patients with pT1b (64.8%; 95% CI, 40.0%–81.4%) than in those with pT1a (89.0%; 95% CI, 72.1%–95.9%; P = .002; Figure 5, A), using the MM method. Intergroup differences were not observed (P = .30), and the estimated 3-year PFS rate was 75.0% (95% CI, 12.8%–96.1%) in pT1m cases and 81.0% (95% CI, 67.6%–89.3%) in pT1e cases (Figure 5, B), using the DOI method. Disease progression occurred in only 1 of the 22 cases of pT1m. The 3-year PFS rate was significantly lower in patients with pT1-bpap (73.1%; 95% CI, 55.8%–84.5%) than in those with pT1-cpap (100%; 95% CI, not available; P = .01; Figure 5, C), using the PS method. Disease progression did not occur in pT1-cpap cases.

Figure 5

Kaplan-Meier curve of the PFS rate stratified by pT1 substage, using the MM (A), depth of invasion (B), and PS (C) methods. Abbreviations: MM, muscularis mucosae; PFS, progression-free survival; PS, stalk of the papillary lesion; pT1a, invasion into a shallower layer than the MM; pT1b, invasion into or beyond the MM; pT1-bpap, invasion beyond the base of the PS; pT1-cpap, invasion confined to the stroma of the PS; pT1e, extensive invasion; pT1m, microinvasion.

Figure 5

Kaplan-Meier curve of the PFS rate stratified by pT1 substage, using the MM (A), depth of invasion (B), and PS (C) methods. Abbreviations: MM, muscularis mucosae; PFS, progression-free survival; PS, stalk of the papillary lesion; pT1a, invasion into a shallower layer than the MM; pT1b, invasion into or beyond the MM; pT1-bpap, invasion beyond the base of the PS; pT1-cpap, invasion confined to the stroma of the PS; pT1e, extensive invasion; pT1m, microinvasion.

Close modal

Univariate and Multivariate Cox Proportional Hazard Regression Analyses for Progression

Results of univariate and multivariate Cox proportional hazard regression analyses for progression are shown in Table 2. Only the MM method was an independent prognostic factor for disease progression in multivariate analysis (HR, 3.6920; P = .03). The PS method was not included in the analysis because disease progression was not observed in the pT1-cpap group.

Table 2

Univariate and Multivariate Cox Proportional Hazard Regression Analysis for Progression

Univariate and Multivariate Cox Proportional Hazard Regression Analysis for Progression
Univariate and Multivariate Cox Proportional Hazard Regression Analysis for Progression

Recurrence-Free Survival and pT1 Subclassification

Recurrence occurred in 36 of the 106 patients (34.0%), and the estimated 2-year RFS rate was 57.7% (Table 1). No significant difference was observed between the 2 substages for all 3 pT1 subclassification methods (P = .73, .79, .40 for the MM, DOI, and PS methods, respectively). Using the MM method, the 2-year RFS rates were estimated at 57.1% (95% CI, 42.6%–69.1%) and 59.9% (95% CI, 37.5%–76.5%) for pT1a and pT1b cases, respectively (Figure 6, A). With the DOI method, RFS rates were 60.8% (95% CI, 31.0%–81.0%) and 56.7% (95% CI, 43.4%–68.0%) for pT1m and pT1e cases, respectively (Figure 6, B). Finally, applying the PS method, the RFS rates were 47.9% (95% CI, 26.4%–66.6%) and 62.0% (95% CI, 47.6%–73.5%) for pT1-cpap and pT1-bpap cases, respectively (Figure 6, C).

Figure 6

Kaplan-Meier curve of the RFS rate stratified by pT1 substage, using the MM (A), depth of invasion (B), and PS (C) methods. Abbreviations: MM, muscularis mucosae; PS, stalk of the papillary lesion; pT1a, invasion into a shallower layer than the MM; pT1b, invasion into or beyond the MM; pT1-bpap, invasion beyond the base of the PS; pT1-cpap, invasion confined to the stroma of the PS; pT1e, extensive invasion; pT1m, microinvasion; RFS, recurrence-free survival.

Figure 6

Kaplan-Meier curve of the RFS rate stratified by pT1 substage, using the MM (A), depth of invasion (B), and PS (C) methods. Abbreviations: MM, muscularis mucosae; PS, stalk of the papillary lesion; pT1a, invasion into a shallower layer than the MM; pT1b, invasion into or beyond the MM; pT1-bpap, invasion beyond the base of the PS; pT1-cpap, invasion confined to the stroma of the PS; pT1e, extensive invasion; pT1m, microinvasion; RFS, recurrence-free survival.

Close modal

Univariate and Multivariate Cox Proportional Hazard Regression Analyses for Recurrence

Results of the univariate and multivariate Cox proportional hazard regression analyses for recurrence are shown in Table 3. A history of upper urinary tract urothelial carcinoma and BCa was predictive of recurrence in the univariate analysis; however, none of the pT1 subclassification methods predicted recurrence. None of the clinicopathologic factors showed predictive significance in the multivariate analysis.

Table 3

Univariate and Multivariate Cox Proportional Hazard Regression Analysis for Recurrence

Univariate and Multivariate Cox Proportional Hazard Regression Analysis for Recurrence
Univariate and Multivariate Cox Proportional Hazard Regression Analysis for Recurrence

We examined the prognostic value of the 3 pT1 subclassification methods using ERBT specimens. The ERBT specimens enabled the precise diagnosis of all pT1 subclassifications. Multivariate analysis showed that the MM method was the sole independent prognostic factor for disease progression. Younes et al6  first proposed the MM method in 1990, and its predictive value in cTURBT specimens has been reported.4,5,9  However, the MM method has low interobserver reproducibility and diagnostic accuracy owing to fragmentation and cauterization of the cTURBT specimens.9,1416  ERBT specimens are hypothesized to overcome the limitation of cTURBT specimens in pathologic diagnosis. Previous studies have shown that the MM method is more accurately diagnosed in ERBT than in cTURBT specimens.16,17  Research examining the predictive value of the MM method in ERBT specimens is extremely limited. A previous study where one-fourth of patients underwent ERBT showed the prognostic value of the MM method in T1 BCa; however, ERBT cases were not analyzed separately from cTURBT cases.19  Yasui et al23  reported better PFS in pT1a cases in a small single-institutional cohort (n = 56), in accordance with our results. Therefore, ERBT for T1 BCa with accurate pT1 subclassification may lead to more precise prognostication and appropriate postoperative planning.

We found that invasion beyond the base of PS was associated with a worse PFS when using the PS method. Remarkably, the estimated 3-year PFS rate in the pT1-cpap group was 100%. Our study was the first to assess the prognostic utility of the PS method using ERBT specimens. Using cTURBT specimens, Lawless et al24  also showed better PFS in the pT1-cpap group and reported no progression among 20 cases of pT1-cpap during the 1.8-year median follow-up period. These results suggest that the PS method is useful for identifying better prognosis groups. The reason for the lower frequency of progression in pT1-cpap cases is unknown; however, one possible hypothesis is attributed to the difference in histology. The stromal component of the PS is composed of edematous, loose connective tissue with fine capillaries.24,25  In contrast, the preexisting subepithelial connective tissue layer contains dense collagen fibers, smooth muscles, and a relatively large vascular plexus. This histologic difference may contribute to differences in the potential for progression.

None of the pT1 subclassification methods examined in this study was significantly prognostic for recurrence. Univariate Cox proportional hazard regression analysis showed that any history of bladder or upper urinary tract tumors was a prognosticator of recurrence. Several previous studies also reported that the pT1 subclassification was not predictive of recurrence, regardless of predictivity for progression.4,9,24,26,27  These studies and our study suggest that other factors, including a history of any urinary tract tumor, multiplicity, and adjuvant therapies such as bacillus Calmette-Guérin instillation therapy, are more strongly related to recurrence than the pT1 subclassification.4,25 

This is the first study that investigated prognostic values of multiple methods of pT1 subclassification in ERBT specimens. Notably, substages were evaluable by using the 3 different methods in all cases. A more accurate pT1 subclassification is possible in ERBT than in cTURBT specimens.1618  Therefore, ERBT for T1 BCa with an accurate diagnosis of the pT1 substage may help establish an appropriate and personalized postoperative plan for patients. Using the MM method, PS method, or a combination of both to define patients with better prognoses may avoid unnecessary reTUR and reduce the economic burden on society. Furthermore, the pT1 subclassification may identify patients with worse prognoses for whom additional treatment may be required, including early radical cystectomy and bladder instillation therapy. Furthermore, ERBT specimens are advantageous owing to evaluable surgical margins. As previously reported, the vertical surgical margin status was evaluable in 103 of 106 cases (97%), and the surgical margin status was a prognosticator for progression.20  Therefore, the surgical margin status, in combination with pT1 subclassification, can be used to plan postsurgical management in patients with T1 BCa treated with ERBT.

The major limitations of this study were the small cohort size and selection bias for ERBT; specifically, a small cohort size reduces statistical power. Moreover, Cox proportional hazard regression analysis for progression could not be performed for the PS method because progression did not occur in 1 subgroup. Furthermore, selection bias may have occurred upon excluding cases with larger tumors and suspected muscle invasion owing to technical limitations in the ERBT procedure. In addition, selection bias for ERBT can show a markedly higher frequency of a noninvasive papillary lesion–associated tumor. Further studies with larger cohorts are required.

In conclusion, we confirmed that MM invasion is a strong prognosticator for disease progression in patients with pT1 BCa, using ERBT specimens. We showed that the PS method may also prognosticate disease progression. Accurate pT1 subclassification using ERBT specimens may enable appropriate and personalized care for patients with T1 BCa.

We would like to thank Editage (www.editage.com) for English-language editing.

1.
Kirkali
Z,
Chan
T,
Manoharan
M,
et al.
Bladder cancer: epidemiology, staging and grading, and diagnosis
.
Urology
.
2005
;
66
(
6 suppl 1
):
4
34
.
2.
van Rhijn
BW,
Burger
M,
Lotan
Y,
et al.
Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy
.
Eur Urol
.
2009
;
56
(
3
):
430
442
.
3.
Babjuk
M,
Burger
M,
Compérat
EM,
et al.
European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)—2019 Update
.
Eur Urol
.
2019
;
76
(
5
):
639
657
.
4.
Martin-Doyle
W,
Leow
JJ,
Orsola
A,
et al.
Improving selection criteria for early cystectomy in high-grade T1 bladder cancer: a meta-analysis of 15,215 patients
.
J Clin Oncol
.
2015
;
33
(
6
):
643
650
.
5.
Parizi
MK,
Enikeev
D,
Glybochko
PV,
et al.
Prognostic value of T1 substaging on oncological outcomes in patients with non-muscle-invasive bladder urothelial carcinoma: a systematic literature review and meta-analysis
.
World J Urol
.
2020
;
38
(
6
):
1437
1449
.
6.
Younes
M,
Sussman
J,
True
L.
The usefulness of the level of the muscularis mucosae in the staging of invasive transitional cell carcinoma of the urinary bladder
.
Cancer
.
1990
;
66
(
3
):
543
548
.
7.
van der Aa
MNM,
van Leenders
GJLH,
Steyerberg
EW,
et al.
A new system for substaging pT1 papillary bladder cancer: a prognostic evaluation
.
Hum Pathol
.
2005
;
36
(
9
):
981
986
.
8.
Hermann
GG,
Horn
T,
Steven
K.
The influence of the level of lamina propria invasion and the prevalence of p53 nuclear accumulation on survival in stage T1 transitional cell bladder cancer
.
J Urol
.
1998
;
159
(
1
):
91
94
.
9.
Colombo
R,
Hurle
R,
Moschini
M,
et al.
Feasibility and clinical roles of different substaging systems at first and second transurethral resection in patients with T1 high-grade bladder cancer
.
Eur Urol Focus
.
2018
;
4
(
1
):
87
93
.
10.
Amin
MB.
The AJCC Cancer Staging Manual. 8th ed
.
Chicago
:
American Joint Committee on Cancer;
2017
:
763
.
11.
WHO Classification of Tumours Editorial Board
.
WHO Classification of Tumours: Urinary and Male Genital Tumours. 5th ed
.
Lyon
:
International Agency for Research on Cancer;
2022
:
164
.
12.
Compérat
E,
Amin
MB,
Epstein
JI,
et al.
The Genitourinary Pathology Society update on classification of variant histologies, T1 substaging, molecular taxonomy, and immunotherapy and PD-L1 testing implications of urothelial cancers
.
Adv Anat Pathol
.
2021
;
28
(
4
):
196
208
.
13.
NCCN Guidelines
,
Bladder Cancer, Version 2.2022
. .
14.
Angulo
J,
Lopez
J,
Grignon
D,
et al.
Muscularis mucosa differentiates two populations with different prognosis in stage T1 bladder cancer
.
Urology
.
1995
;
45
(
1
):
47
53
.
15.
Platz
CE,
Cohen
MB,
Jones
MP,
et al.
Is microstaging of early invasive cancer of the urinary bladder possible or useful?
Mod Pathol
.
1996
;
9
(
11
):
1035
1039
.
16.
Yanagisawa
T,
Yorozu
T,
Miki
J,
et al.
Feasibility and accuracy of pathological diagnosis in en-bloc transurethral resection specimens versus conventional transurethral resection specimens of bladder tumour: evaluation with pT1 substaging by 10 pathologists
.
Histopathology
.
2021
;
78
(
7
):
943
950
.
17.
Yanagisawa
T,
Mori
K,
Motlagh
RS,
et al.
En bloc resection for bladder tumors: an updated systematic review and meta-analysis of its differential effect on safety, recurrence and histopathology
.
J Urol
.
2022
;
207
(
4
):
754
768
.
18.
Gakis
G,
Karl
A,
Bertz
S,
et al.
Transurethral en bloc submucosal hydrodissection vs conventional resection for resection of non-muscle-invasive bladder cancer (HYBRIDBLUE): a randomised, multicentre trial
.
BJU Int
.
2020
;
126
(
4
):
509
519
.
19.
Yanagisawa
T,
Miki
J,
Yorozu
T,
et al.
Vertical lamina propria invasion diagnosed by en bloc transurethral resection is a significant predictor of progression for pT1 bladder cancer
.
J Urol
.
2021
;
205
(
6
):
1622
1628
.
20.
Yanagisawa
T,
Sato
S,
Hayashida
Y,
et al.
Do we need repeat transurethral resection after en bloc resection for pathological T1 bladder cancer?
BJU Int
.
2023
;
131
(
2
):
190
197
.
21.
Paner
GP,
Ro
JY,
Wojcik
EM,
et al.
Further characterization of the muscle layers and lamina propria of the urinary bladder by systematic histologic mapping: implications for pathologic staging of invasive urothelial carcinoma
.
Am J Surg Pathol
.
2007
;
31
(
9
):
1420
1429
.
22.
Kanda
Y.
Investigation of the freely available easy-to-use software ‘EZR' for medical statistics
.
Bone Marrow Transpl
.
2012
;
48
(
3
):
452
458
.
23.
Yasui
M,
Ohta
J,
Aoki
S,
et al.
Prognosis of patients with T1 bladder cancer after en bloc transurethral resection of bladder tumor stratified by invasion to the level of the muscularis mucosa
.
Int Urol Nephrol
.
2021
;
53
(
6
):
1105
1109
.
24.
Lawless
M,
Gulati
R,
Tretiakova
M.
Stalk versus base invasion in pT1 papillary cancers of the bladder: improved substaging system predicting the risk of progression
.
Histopathology
.
2017
;
71
(
3
):
406
414
.
25.
Saito
W,
Amanuma
M,
Tanaka
J,
et al.
Histopathological analysis of a bladder cancer stalk observed on MRI
.
Magn Reson Imaging
.
2000
;
18
(
4
):
411
415
.
26.
Soukup
V,
Dušková
J,
Pešl
M,
et al.
The Prognostic value of T1 bladder cancer substaging: a single institution retrospective study
.
Urol Int
.
2014
;
92
(
2
):
150
156
.
27.
Orsola
A,
Werner
L,
de Torres
I,
et al.
Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients
.
Brit J Cancer
.
2015
;
112
(
3
):
468
474
.

Competing Interests

The authors have no relevant financial interest in the products or companies described in this article.