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'Solitary' Ta-T1 G1 bladder tumour--history and long-term prognosis
Abstract
Natural history of 'solitary', histological grade 1, stage Ta-T1 transitional cell carcinoma of the bladder was studied in 198 patients retrospectively over a period from 1975 to 1987. Three patterns of tumour behaviour were evident. In 56% of patients the tumour did not recur following the initial resection. Twenty-one percent developed recurrences localised to the site of the original tumour. This group became tumour-free by 5 years and remained so thereafter. The remaining 23% continued to produce recurrent tumours up to 10 years at different sites in the bladder. The actuarial percentage of patients who remained continuously free of tumour after the initial resection was 53% at 5 years and 51% at 10 years. The results of this study suggest that cytoscopic follow-up may be discontinued in patients who remain continuously tumour-free for 5 years.
... 15 Nine patients (5%) died of bladder cancer among 155 patients with Grade 1 urothelial carcinoma. 16 Mufti et al. 23 reviewed 198 patients with Grade 1 urothelial carcinoma and found that only 53% of patients remained cancer free at 5 years; the actuarial cancer mortality rate was 4%. Papillary urothelial neoplasms of LMP appears to have a predilection for the ureteric orifice, 23 referred as the "typical primary site" by Page et al. 24 Sixty-nine percent of Grade 1 urothelial carcinomas were centered around the ureteric orifice, and tumor was found in the anterior wall in 2 patients (1%). ...
... Papillary urothelial neoplasms of LMP appears to have a predilection for the ureteric orifice, 23 referred as the "typical primary site" by Page et al. 24 Sixty-nine percent of Grade 1 urothelial carcinomas were centered around the ureteric orifice, and tumor was found in the anterior wall in 2 patients (1%). 23 Dome appeared to be an uncommon location for LMP tumors (3%) in the current study. With a median follow-up of 11.7 years, we found that 4 patients developed invasive urothelial carcinoma, including 2 with muscleinvasive cancer. ...
BACKGROUND
Knowledge of the long term outcomes of patients with papillary urothelial neoplasms of low malignant potential (LMP) is limited.METHODS
The authors studied 112 consecutive patients who were diagnosed with papillary urothelial neoplasms of LMP (formerly Ta, World Health Organization Grade 1 of 3 papillary urothelial carcinoma) at the Mayo Clinic between 1958 and 1963. All histologic slides were reviewed and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system.RESULTSPatient age at diagnosis ranged from 33 to 99 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 12.8 years (range, 0.1–35 years; median, 11.7 years). Twelve patients had biopsy-proven, noninvasive urothelial carcinoma; 17 patients had cystoscopically detected recurrences (all were treated by fulguration without biopsy); and 4 patients developed invasive urothelial carcinoma (including 2 with muscle-invasive carcinoma). Twelve (75%) of 16 patients with biopsy-proven recurrence or progression had cancer dedifferentiation, which resulted in a diagnosis of higher grade cancer than was indicated on initial biopsies. The mean interval from initial diagnosis to development of invasive carcinoma was 13.3 years (range, 10–14 years). Three patients died of bladder cancer.CONCLUSIONS
Patients with papillary urothelial neoplasms of LMP have increased risks of local recurrence, progression, and death from bladder carcinoma. Long term clinical follow-up may be indicated for patient management. [See editorial on pages 1890–2 and related article on pages 2098–101, this issue.] Cancer 1999;86:2102–8. © 1999 American Cancer Society.
... Repeated transurethral resection is harmful for patients, however, and occasionally, the disease progresses after recurrence. 19,20 BCG can be adapted to these low-risk patients when adverse effects can be minimized. In conclusion, our study suggests that 40 mg of BCG Tokyo 172 strain might be suitable, at least for initial treatment, for the prophylaxis of bladder cancer recurrence after transurethral resection. ...
Intravesical instillation of bacillus Calmette-Guérin (BCG) is the most efficient strategy for prophylaxis of superficial bladder cancer recurrence. Adverse effects of BCG are major obstacles, but the reduction of BCG dose could minimize these effects. The efficacy and adverse effects of half-dose (40 mg) BCG, Tokyo 172 strain, were prospectively evaluated.
A total of 93 patients with superficial bladder cancer (pTa or pT1) were sequentially assigned to receive either 40 or 80 mg of BCG after transurethral resection. BCG was administered weekly for 6 weeks postoperatively. Eighty patients observed longer than 12 months after BCG therapy (41, 40 mg group; 39, 80 mg group) were analyzed.
BCG therapy course was completed in 71 patients. Tumor recurrence was recognized in 11 of 40 patients in the 40 mg group and in 5 of 31 patients in the 80 mg group. There was no significant difference in tumor recurrence rate between the two groups (P = 0.547). BCG therapy was withdrawn in 1 patient in the 40 mg group and in 8 patients in the 80 mg-group because of BCG-related adverse effects. The morbidity of BCG-related toxicity was significantly higher in the 80 mg group.
Half-dose of BCG Tokyo 172 strain had a similar efficacy and its toxicity was significantly lower compared to the standard dose. Thus, half-dose of this strain might be suitable, at least for initial BCG therapy, for the prophylaxis of bladder cancer recurrence. Further study would be necessary to clarify the efficacy of low-dose instillation in high-risk patients.
Carcinoma of the urinary bladder is the fourth most common malignancy in men, accounting for an estimated 60,490 new cases and 12,240 cancer deaths in the United States in 2018. Significant progress has been made in the diagnosis and treatment of bladder cancer. Bladder cancer is morphologically heterogeneous; more than 90% of bladder cancer cases are urothelial (transitional cell) carcinoma, whereas primary squamous cell carcinoma, adenocarcinoma, small cell carcinoma, and other tumors are less common. The classification system of urinary bladder neoplasia used in this chapter has been modified according to the 2016 World Health Organization (WHO) classification of tumors of the urinary system.
The human urinary bladder is subject to a unique and extraordinarily diverse array of congenital, inflammatory, metaplastic, and neoplastic abnormalities. This book provides contemporary, comprehensive, and evidence-based practice information for pathologists, urologists, oncologists, and other medical professionals. In Bladder Pathology, a full spectrum of pathologic conditions that afflict the bladder and urothelium are described and lavishly illustrated. With its emphasis on diagnostic criteria and differential diagnoses, this book is of particular value to practicing pathologists-assisting in the pathologist's recognition, understanding, and accurate interpretation of the light microscopic findings in bladder specimens. Features and benefits of this new volume include: • 1,741 high-quality, color illustrations and 112 tables to illustrate the wide range of pathologic and clinical features in the urinary tract • An evidence-based approach to diagnosis and patient management for infectious, nonneoplastic, and neoplastic conditions • Recent advances in the molecular genetics of the urinary bladder with discussion of their current or potential impact on diagnosis and personalized patient care • With emphasis on the scientific validation of current diagnostic methods and their direct application in clinical practice, Bladder Pathology is a cutting-edge resource that not only offers comprehensive research and clinical information for practicing surgical pathologists, urologists, oncologists, and their clinical colleagues, but also captures a genuine sense of excitement about recent advances in this vital, ever-evolving field.
Nearly half of all bladder tumors are noninvasive (stage pTa) papillary neoplasms of urothelial origin. These tumors have been intensively investigated for many decades, and a number of concepts regarding their biologic behavior and prognosis have been well established. Prognosis for these tumors is influenced by tumor size, tumor multifocality, recurrence status, coexistence of carcinoma in situ, and histologic tumor grade [1–6]. The first four elements are straightforward. However, there has been a long-standing lack of agreement among pathologists concerning the ideal system for grading these tumors. A uniform grading system for bladder cancer will allow for valid comparison of treatment results among different centers. The 1973 WHO classification is preferred by some authors because it allows comparison of results between different clinical centers. It is a robust, time-tested, and reasonably reproducible method for pathologic reporting of bladder tumors. The 1998 WHO/ISUP classification of bladder tumors, and its adoption in the 2004 WHO classification, has been the subject of considerable controversy [3, 7–28]. In particular, there is poor interobserver agreement in the diagnostic categories of papillary urothelial neoplasm of low malignant potential (PUNLMP) and low-grade urothelial carcinoma, two new categories in the 2004 WHO system [8, 9, 12, 29–34]. Use of both the 1973 and 2004 WHO classifications (former 1998 ISUP/WHO) has been recommended by some [3, 8, 11, 12, 35–37]. We recently introduced a new four-tiered grading system, which expands previous grading systems to include an additional category of noninvasive papillary carcinomas with exceptionally abnormal cytologic characteristics (Fig. 8.1, Table 8.1) [38]. This new grading system has the combined strengths of both 1973 WHO and 2004 WHO grading system [38].
The knowledge about the evolution and long-term survival of patients with papillary utothelial neoplasm of low malignant potential of the bladder is still limited due to the recent implantation of this term.Material And Methods
Patients with superficial bladder cancer treated at HRU Reina Sofía between 1990 and 1995 were reviewed. We found 50 patients with the diagnostic criteria of “papillary urothelial neoplasm of low malignant potential” according to the classification of the 1998 World Health Organization/International Society of Urologic Pathology (WHO/ISUP). There were no patients with a prior history or coexistent urothelial dysplasia, carcinoma in situ, or invasive urothelial carcinomaResultsPatient mean age at diagnosis was 62.08 years old (range: 32-85). Male to female ratio was 7:1 (44 male and 6 female). No evidence of neoplasia in the upper urinary tract was found in any patient. Thirty nine patients (78%) had one or two tumor implants, and 11 patients (22%) had three or more. Mean tumor size was 2.26 cm (range: 1-5). There were recurrence without progression in 17 cases (34%) and recurrence with progression in two patients (4%). Mean survival was 78 months (range: 38-117) and two patients died of bladder cancerConclusions
Patients with papillary urothelial neoplasm of low malignant potential have increased risk of local recurrence, progression, and dying of bladder cancer. Long-term follow-up is recommended in the postoperative management of these patients
Fragestellung: Durch eine 2nd look transurethrale Resektion (TUR) beim oberflächlichen Blasenkarzinom erwartet man eine bessere Tumorkontrolle durch eine Reduktion der sogenannten Tumorpersister beziehungsweise Frührezidive. Wir durchleuchteten kritisch die Rolle einer Routine-second-Look-TUR bei oberflächlichem Blasenkarzinoms.
Material und Methode: Zwischen 1/1996 und 12/1998 wurden 75 Patienten mit erstmalig aufgetretenem oberflächlichen Blasenkarzinoms in eine retrospektive Analyse aufgenommen. Bei allen Patienten wurde 8 Wochen nach initialer TUR eine Second-Look-TUR durchgeführt. Wir verglichen Tumorstadien, Grading, Veränderung der Histopathologie und die Präsenz von Residualtumoren bzw. Frührezidiven nach initialer TUR.
Ergebnisse: Bei 24 Patienten (32 %) wurde in der histologischen Auswertung der Second-Look-TUR neuerlich ein oberflächliches Blasenkarzinom gefunden. Aufgelistet nach initialem Tumorstadium und Grading fanden wir bei 10 % der pTaG1, 20,5 % der pTaG2 und 50 % der pTaG3, 50 % der pT1G2 und 52,6 % der pT1G3-Patienten einen persistierenden bzw. rezidivierenden Tumor. In der Nachresektion von makroskopisch unauffälligen initialen pTa/1-G1- und -G2-TUR-Arealen fand sich in keinem der Fälle ein Tumor. Lediglich bei 2 von 75 Patienten wurde ein Tumorpersister bzw. Rezidiv nicht auch makroskopisch, sondern erst in der histologischen Auswertung verifiziert. In beiden Fällen zeigte die Ersthistologie einen G3-Tumor und die Auswertung der second look TUR ein Carcinoma in situ (CIS).
Schlussfolgerung: In einer signifikanten Anzahl von Patienten mit oberflächlichem Blasenkarzinoms fanden sich Tumorpersister bzw. Frührezidive. Da jedoch bei allen Patienten mit initialem G1- und G2-Tumor persistierende bzw. rezidivierende Karzinome primär makroskopisch detektiert wurden, sollte eine Routine-second-Look-TUR für Patienten mit primär erhöhtem Rezidivrisiko (pTaG3, pT1G1-3) vorbehalten sein.
A uniform grading system for bladder cancer will allow for valid comparison of treatment results among different centers. The introduction of the World Health Organization (2004)/International Society of Urological Pathology classification is a welcome step toward standardization of treatment and follow-up regimens. The greatest source of controversy with the World Health Organization (2004)/International Society of Urological Pathology classification system centers on the diagnosis of papillary urothelial neoplasm of low malignant potential. Some feel that papillary urothelial neoplasm of low malignant potential terminology increases the complexity of histologic grading and does not accurately reflect biologic potential. Papillary urothelial neoplasm of low malignant potential is a low-grade papillary urothelial neoplasm with a substantial incidence of recurrence and progression. In the distinction of papillary urothelial neoplasm of low malignant potential from noninvasive low-grade papillary urothelial carcinoma, there is considerable interobserver variability. For these reasons, some investigators believe that papillary urothelial neoplasm of low malignant potential is, in essence, an entity that was previously designated grade 1 urothelial carcinoma in the World Health Organization 1973 grading system. In addition, treatment and follow-up regimens for patients with papillary urothelial neoplasm of low malignant potential do not typically differ from those prescribed for low-grade, noninvasive urothelial carcinoma, further minimizing the clinical need for the papillary urothelial neoplasm of low malignant potential distinction to be made. We propose abandonment of the terminology "papillary urothelial neoplasm of low malignant potential" in bladder tumor classification. Full-genome searches for prognostic and predictive molecular gene expression signatures as cancer markers have shown significant promise. Recent advances in the molecular grading of these tumors may eventually supplant traditional morphologic grading systems, allowing a more precise and objective assessment of the tumors' biologic potentials.
A retrospective study was done on 176 patients with primary stages Ta and T1 bladder cancer treated between 1963 and 1972. One patient was lost to followup after 6 years, while the remainder were followed to death or for at least 20 years. In 1993, 13 patients had no evidence of disease, 39 died of bladder cancer and 123 died of intercurrent disease. Of 77 patients with a primary noninfiltrating tumor and 99 with a primary lamina propria invasive tumor 9 (11%) and 30 (30%), respectively, died of bladder cancer. Recurrences were noted on 10 or more cystoscopic studies in 16 patients and 10 died of bladder cancer 3.5 to 19 years after the primary transurethral resection. A total of 14 patients received repeated thiotepa instillations, all continued to have recurrences and 10 subsequently died of bladder cancer. Only 1 upper tract tumor was diagnosed on routine followup excretory urography. Invasive transitional cell carcinoma of the bladder developed in only 1 of 59 patients who had been tumor-free for 5 years. The results indicate that patients with recurrences on 10 or more cystoscopic studies will continue to have recurrences until death or cystectomy. Recurrence more than 4 years after the primary tumor operation is another ominous sign. Repeated thiotepa instillations did not influence the course of the disease in patients with a history of multiple recurrences. Followup cystoscopy may be discontinued 5 to 10 years after the last recurrence, at least in patients with a solitary low grade primary tumor. Routine followup urographic studies are neither cost-effective, clinically indicated nor justified in patients with superficial bladder cancer.
We reviewed our series of stage Ta bladder cancer patients with a long-term follow-up in order to clarify the prognosis of these patients, especially those who have repeated recurrences.
A retrospective study was done on 88 patients with stage Ta bladder cancer who were treated between 1971 and 1990 at our hospital. All patients reviewed were followed up for at least 5 years.
Fifty-three patients out of 88 had recurrence, and the number of recurrences ranged from one to eleven. In the first recurrence, the 5- and 10-year recurrence-free rates were 53.4% and 37.1%, respectively. In the second recurrence, those rates were 25.7% and 15.9%, respectively. Comparisons of the recurrence-free rates between the first recurrence and that of more than 2 times yielded statistically significance (p < 0.01). On the other hand, when the recurrence-free rates of those patients showing recurrence more than 2 times were compared no statistical significance was observed among them. In addition, most patients with multiple recurrences also tended to show a long tumor-free period at some point. In eight patients a stage-up of > or = T1 developed during the study period. No characteristics of the tumors, including the multiplicity of the recurrence, was found to correlate with the stage-up.
Most patients with multiple recurrences demonstrated a long tumor-free period at some point, and, moreover, in some of those patients there was also a possibility that no further recurrence occurred. In addition, frequent recurrence was not associated with increased incidence of stage-up. Based on these findings, multiple recurrence is not thought to be an especially ominous sign, and therefore bladder-preserving therapy is indicated for such patients.
Knowledge of the long term outcomes of patients with papillary urothelial neoplasms of low malignant potential (LMP) is limited.
The authors studied 112 consecutive patients who were diagnosed with papillary urothelial neoplasms of LMP (formerly Ta, World Health Organization Grade 1 of 3 papillary urothelial carcinoma) at the Mayo Clinic between 1958 and 1963. All histologic slides were reviewed and fulfilled the diagnostic criteria of the 1998 World Health Organization/International Society of Urological Pathology classification system.
Patient age at diagnosis ranged from 33 to 99 years (mean, 65 years). The male-to-female ratio was 3:1. The mean follow-up was 12.8 years (range, 0.1-35 years; median, 11.7 years). Twelve patients had biopsy-proven, noninvasive urothelial carcinoma; 17 patients had cystoscopically detected recurrences (all were treated by fulguration without biopsy); and 4 patients developed invasive urothelial carcinoma (including 2 with muscle-invasive carcinoma). Twelve (75%) of 16 patients with biopsy-proven recurrence or progression had cancer dedifferentiation, which resulted in a diagnosis of higher grade cancer than was indicated on initial biopsies. The mean interval from initial diagnosis to development of invasive carcinoma was 13.3 years (range, 10-14 years). Three patients died of bladder cancer.
Patients with papillary urothelial neoplasms of LMP have increased risks of local recurrence, progression, and death from bladder carcinoma. Long term clinical follow-up may be indicated for patient management.
The knowledge about the evolution and long-term survival of patients with papillary utothelial neoplasm of low malignant potential of the bladder is still limited due to the recent implantation of this term.
Patients with superficial bladder cancer treated at HRU Reina Sofía between 1990 and 1995 were reviewed. We found 50 patients with the diagnostic criteria of "papillary urothelial neoplasm of low malignant potential" according to the classification of the 1998 World Health Organization/International Society of Urologic Pathology (WHO/ISUP). There were no patients with a prior history or coexistent urothelial dysplasia, carcinoma in situ, or invasive urothelial carcinoma.
Patient mean age at diagnosis was 62.08 years old (range: 32-85). Male to female ratio was 7:1 (44 male and 6 female). No evidence of neoplasia in the upper urinary tract was found in any patient. Thirty nine patients (78%) had one or two tumor implants, and 11 patients (22%) had three or more. Mean tumor size was 2.26 cm (range: 1-5). There were recurrence without progression in 17 cases (34%) and recurrence with progression in two patients (4%). Mean survival was 78 months (range: 38-117) and two patients died of bladder cancer.
Patients with papillary urothelial neoplasm of low malignant potential have increased risk of local recurrence, progression, and dying of bladder cancer. Long-term follow-up is recommended in the postoperative management of these patients.
Surveillance of transitional cell carcinoma of the bladder forms a major part of the workload of many urology units. Unfortunately, the policy for long-term surveillance of these cancers is neither clear nor agreed upon in the absence of evidence base. Our study was performed to provide current national practice data, and begin the debate on consensus guidelines.
A questionnaire was sent to Consultant Urologists (CUs) in the UK and Ireland (n=501) asking about their policy on the long-term surveillance of different bladder tumours once patients are free of recurrence.
A 73% response rate was observed (365/501). Views varied considerably. They ranged from life long cystoscopic surveillance for low-stage low-grade tumours (pTaG1) to discharge after 5 years (or less) of a recurrence-free period for pT1G3 tumour. Once long-term surveillance with cystoscopy had been discontinued, 55% of CUs felt no role was indicated for urine cytology in further follow up, whereas 17% would use it for all tumour types and 28% are selective.
Our study has shown the complete lack of consensus regarding the long-term surveillance of bladder cancer in the UK and Ireland. This has major implications for policy making, resources allocation and cancer survival. We highlight the need for national guidelines in this area for optimal surveillance of bladder cancer, as a good prospective evidence-based data will not be available for many years. We believe our study might form the basis for discussion on such guidelines.
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