Clinical value of pathologic changes after intravesical BCG therapy of superficial bladder cancer

doi:10.1016/0090-4295(92)90523-Y

Urology

Volume 40, Issue 2, August 1992, Pages 175-179

https://doi.org/10.1016/0090-4295(92)90523-Y Get rights and content

Abstract

Bladder pathologic features related to intravesical bacillus Calmette-Guerin (BCG) therapy in superficial bladder cancer (Ta, T1, Tis) were evaluated and related to clinical outcome. A total of 105 patients were treated with 75 mg Pasteur BCG weekly for six consecutive weeks. When tumor was not demonstrated a maintenance course was given. An additional six-week course was given when tumor recurrence or persistence, without progression, was observed after the induction course. An inflammatory change in the bladder was the most common pathologic finding. Granuloma was the only specific BCG-related feature and did not appear to be a prognostic factor because of low incidence (24 %) and lack of correlation with clinical course. Dysplasia occurred more frequently (57 % ) in nonresponder patients and (26 %, ) in responder patients, often heralding recurrence of tumor. All patients showing concurrent squamous and/or glandular metaplasia were unresponsive to BCG therapy. Histology and cytology did not correlate perfectly: cytology was ineffective in low-grade tumors and improved diagnostic accuracy, particularly when dysplasia was histologically evident.

References (19)

A. Morales et al.
Intracavitary bacillus Calmette-Guerin in the treatment of superficial bladder tumors
J Urol
(1976)
D.L. Lamm
Bacillus Calmette-Guerin immunotherapy for bladder cancer
J Urol
(1985)
S.A. Brosman
The use of bacillus Calmette-Guerin in the therapy of bladder carcinoma in situ
J Urol
(1985)
H.W. Herr
Long-term effect of intravesical bacillus Calmette-Guerin on flat carcinoma in situ of the bladder
J Urol
(1986)
L.R. Kavoussi
Results of 6 weekly intravesical bacillus Calmette-Guerin instillations on the treatment of superficial bladder tumors
J Urol
(1988)
H.W. Herr
Superficial bladder cancer treated with bacillus Calmette-Guerin: a multivariate analysis of factors affecting tumor progression
J Urol
(1989)
W.J. Catalona
Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer
J Urol
(1987)
F. Pagano
A low-dose bacillus Calmette-Guerin regimen in superficial bladder cancer therapy: is it effective?
J Urol
(1991)
J.M. Lage
Histological parameters and pitfalls in the interpretation of bladder biopsies in bacillus Calmette-Guerin treatment of superficial bladder cancer
J Urol
(1986)

There are more references available in the full text version of this article.

Cited by (21)

The natural course of bacillus Calmette-Guérin induced bladder lesions: A long-term follow-up study and systematic review
2023, Asian Journal of Urology
Bacillus Calmette-Guérin (BCG) instillation is the standard adjuvant treatment for intermediate- and high-risk non-muscle-invasive bladder cancer after transurethral resection. Nevertheless, its toxicity often causes bladder complications. On follow-up cystoscopy, post-BCG bladder lesions can be pathologically benign, urothelial carcinoma recurrence, or other types of bladder malignancy. Only a small number of case reports have been published on post-BCG bladder lesions. Their clinical features, natural course, and management remain unknown.
We retrospectively studied cystoscopic videos and medical records of BCG-treated bladder cancer patients at our center. During a long-term follow-up, we took biopsies on tumor-like lesions and described their changes. In addition, we summarized previous studies on post-BCG bladder lesions by systematic literature searching and review.
We described a series of three cases with post-BCG bladder lesions mimicking tumor recurrence from a total of 38 cases with follow-up data for more than 5 years. Those lesions could last, grow, or disappear spontaneously, and remain pathological benign for years. In systematic review, we identified and analyzed a total of 15 cases with post-BCG bladder lesions with detailed clinical information. Eleven of the 15 were benign and have a good prognosis with nephrogenic adenoma being the most common pathological type.
Based on previous studies and our experience, benign lesions after BCG instillation cannot distinguish with cancer recurrence by cystoscopy alone, even under narrow band imaging mode. Nonetheless, given most of them have a good prognosis, random biopsy or transurethral resection might be spared in the patients with long-term negative biopsy and urine cytology.
Iatrogenic pathology of the urinary bladder
2018, Seminars in Diagnostic Pathology
Citation Excerpt :
Alternative therapeutic approaches, such as gene therapy or different forms of immunotherapy alone or in different combinations with chemotherapy have been recently adopted although remain as experimental procedures.2–12 Neoadjuvant systemic platinum-based chemotherapy is increasingly applied in most institutions before surgery in an attempt to improve cancer specific survival.42–47 However, there is limited data on tissue and cellular changes related to this therapy, both in the tumor itself and the non-neoplastic urothelium.2–20
Intravesical immunotherapy, chemotherapy, and neoadjuvant systemic chemotherapy are among the most frequent therapeutic procedures to treat malignancies of the urinary bladder. These treatment modalities produce reactive morphologic changes in the urothelium that can mimic urothelial carcinoma in situ, urothelial dysplasia or true invasive urothelial neoplasia. Mitomycin C used after transurethral resection of bladder tumor to reduce recurrences, BCG intravesical immunotherapy to treat high risk non-muscle invasive bladder cancer and urothelial carcinoma in situ, and platinum-based systemic chemotherapy to improve post-cystectomy disease-specific survival some of the causes of therapy related atypia in urinary bladder. In addition, a number of systemic drugs in use to treat other systemic diseases, such as cyclophosphamide used to treat certain auto-immune disorders or hematologic malignancies, or the anesthetics ketamine increasingly used as illegal recreational drug, may produce similarly relevant atypical changes in the urothelium, and therefore, need to be differentiated from intraepithelial neoplasia. Immunohistochemical approach to reactive urothelium from CIS using CK20, p53, and CD44 may also be of utility in the pos-therapy scenario.
What should not be reported as atypia in urine cytology
2015, Journal of the American Society of Cytopathology
Citation Excerpt :
On the other hand, mitomycin and thiotepa usually affect umbrella cells and cause nuclear enlargement, multinucleation, and hyperchromasia of those cells. Treatment effect associated with intravesical bacille Calmette-Guerin (BCG) immunotherapy is well recognized in surgical pathology.48 Because BCG is an attenuated form of bovine tuberculosis bacillus, Mycobacterium bovis, it can cause the formation of granulomas in the lamina propria of the urinary bladder; sometimes these granulomas can be dislodged and can be found in urine specimens (Fig. 7).49
The term “atypia,” although not well characterized, is widely used in diagnostic surgical and cytopathology. Because there are no guidelines regarding when to use this term, in the majority of cases, it is used as a “wastebasket.” This definitely applies to urine cytology, where the reported rate of atypia ranges from 1.9% to 23%. This review lists a number of cytomorphologic findings in urine cytology that are associated with known and specific causes. Urine specimens in which the morphologic changes can be attributed to particular etiologic factors should no longer be classified as “atypical.” These include urine specimens showing reactive umbrella cells or seminal vesicle cells, reactive changes due to stones, cytologic changes characteristic of infectious processes or therapy effect, instrumented urines with pseudopapillary clusters, and urinary diversion specimens.
Intravesical mitomycin therapy for stage t1 and tis high-grade squamous cell carcinoma of the bladder
2014, Clinical Genitourinary Cancer
Citation Excerpt :
However, for patients with non–muscle-invasive SCC who are not surgical candidates or for those who desire bladder-sparing treatment, intravesical chemotherapy should be considered. Although intravesical BCG therapy is known to decrease the recurrence and progression of urothelial non–muscle-invasive disease, including CIS, it has not been shown to be a successful treatment regimen for SCC.7-10 To our knowledge, intravesical mitomycin has not been reported to be a successful treatment for non–muscle-invasive high-risk SCC of the bladder.
Cost-effectiveness of fluorescence in situ hybridization in patients with atypical cytology for the detection of urothelial carcinoma
2013, Journal of Urology
Patients with atypical cytology and equivocal or negative cystoscopy pose a challenge due to uncertainty about the presence of cancer. We determined the cost-effectiveness of using fluorescence in situ hybridization assays to determine the need for biopsy in patients with atypical cytology and equivocal or negative cystoscopy.
Data from 2 large prospective studies evaluating the usefulness of fluorescence in situ hybridization in the setting of atypical cytology to detect urothelial carcinoma were combined. The data were used to calculate sensitivity and specificity for the UroVysion® fluorescence in situ hybridization assay in various clinical scenarios. Cost data were obtained from our institution and Medicare reimbursement rates. Evaluations with or without bladder biopsy and with or without upper tract evaluation were considered.
The study included 263 patients with atypical cytology and equivocal (62) or negative (201) cystoscopy. In patients with equivocal cystoscopy (assuming biopsy was performed in the operating room) biopsy based on fluorescence in situ hybridization results saved $1,740 per patient ($3,267 vs $1,527 per patient) and avoided 42 biopsies compared to biopsy in all patients. If office based biopsies were used then cost savings using fluorescence in situ hybridization results were $95 per patient. Among patients with negative cystoscopy biopsy based on fluorescence in situ hybridization resulted in costs savings of $2,241 per patient, avoiding 167 biopsies, compared to biopsy in all patients. Assuming office based biopsy, the cost savings were $216 per patient.
The decision to perform biopsy based on fluorescence in situ hybridization assay in patients with atypical cytology and equivocal or negative cystoscopy was associated with a significant decrease in bladder cancer associated costs.
Diagnostically Challenging Cases. What are Atypia and Dysplasia?
2013, Urologic Clinics of North America
Citation Excerpt :
BCG is a pleiotropic immune stimulator that can limit tumor progression by recruitment of an antitumoral immune response.28 Microscopically, BCG therapy most notably causes acute and chronic inflammation associated with noncaseating granulomas but may also induce mucosal ulceration, denudation, and reactive urothelial atypia.40 Photodynamic therapy is a newer, less common modality used in treatment of bladder neoplasia.41

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Clinical value of pathologic changes after intravesical BCG therapy of superficial bladder cancer

Abstract

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