Diagnostic Problems of Urine Cytology on Initial Follow-Up after Intravesical Immunotherapy with Calmette-Guérin Bacillus for Superficial Bladder Cancer

Abstract

After transurethral resection or biopsy, patients with recurrent bladder cancer or in situ carcinoma were given topical immunotherapy with low-dose Calmette-Guérin bacillus (BCG). In the recurrence-free interval they were treated with BCG monthly for 1 year and then every 3 months for the next year. Cytological analysis was always performed concomitant with the administration of immunotherapy. In order to evaluate the therapeutic success, cytoscopy and biopsy were performed after the first cycle of BCG and then every 3 months. At the start of topical therapy with BCG, a great increase in the number of inflammatory cells was seen. In urothelial cells the nuclei were enlarged; they were hyperchromatic with sometimes increased and prominent nucleoli, anisocaryosis and a distorted nucleus-plasma ratio. These cytological findings were also made 1 year after initial therapy and slowly diminished in the 2nd year during immunotherapy at 3-month intervals. The accuracy of urine cytology for carcinoma in situ is 80%. Interpretation of cytology in the recurrence-free interval was impaired. When doubtful, the recurrence of a carcinoma in situ under maintenance therapy with BCG must be proved by biospy.

Cytological Changes Induced by Intravesical Bacillus Calmette-Guérin Therapy for Superficial Bladder Cancer

“…Only a few investigators have reported urinary cytology findings after intravesical BCG instillation therapy and the findings were not consistent [15,16]. Mack and Frick [15] reported cytological changes in patients with recurrent bladder cancer and CIS after TUR or biopsy to include enlarged, hyperchromatic nuclei, increased prominent nucleoli, anisonucleosis, distorted nuclear/cytoplasmic ratio of urothelial cells besides significant increase in inflammatory cells.…”

“…Mack and Frick [15] reported cytological changes in patients with recurrent bladder cancer and CIS after TUR or biopsy to include enlarged, hyperchromatic nuclei, increased prominent nucleoli, anisonucleosis, distorted nuclear/cytoplasmic ratio of urothelial cells besides significant increase in inflammatory cells. They stressed that cytological changes Takashi/Schenck/Koshikawa/Nakashima/ Ohshima such as hyperchromasia and distorted nuclear/cytoplasmic ratio, which usually suggest the presence of tumors, impair the interpretation of cytology in patients treated with topical BCG therapy.…”

“…However, only a few studies have concentrated on urinary cytology after intravesical BCG instillation therapy, and the findings were not consistent [15,16]. We therefore evaluated patients who received intravesical BCG therapy for prevention of intravesical recurrence after TUR of superficial bladder cancer, comparing them with individuals receiving intravesical epirubicin therapy.…”

Fluorescence in situ hybridization in diagnostic cytology

“…Unfortunately, the intense inflammatory reaction induced by BCG makes the interpretation of cystoscopic findings difficult because areas of erythema can represent either carcinoma in situ or inflammation. In addition, cytology interpretation is complicated by reactive changes in the cells that make it difficult to distinguish malignant from reactive nonneoplastic cells [28]. A recent study was conducted to determine if FISH could be used to assess response to treatment in patients with superficial bladder cancer receiving BCG or other intravesical therapy [29].…”

The Value of Transurethral Bladder Biopsy after Intravesical Bacillus Calmette-Guérin Instillation Therapy for Nonmuscle Invasive Bladder Cancer: A Retrospective, Single Center Study and Cumulative Analysis of the Literature

“…BCG induced cytological changes are readily detectable within the first 3 months after the last instillation, including enlarged, hyperchromatic nuclei with prominent nucleoli, anisocaryosis, a shifted nucleus-to-plasma ratio and an increase in granulocytes. 15, 16 In a subgroup of samples these changes may be interpreted as positive cytology. In a study of 75 patients with positive urinary cytology after a complete response to BCG for at least 1 year clinically detectable disease developed in 83%.…”