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Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group.

From 1983 to 1986 183 patients with transitiocellular carcinoma of the urinary bladder, category T2-T4a, entered a randomized study. The patients were allocated to receive either preoperative irradiation (40 Gy) followed by cystectomy or radical irradiation (60 Gy) followed by salvage cystectomy in cases of residual tumor. The two randomization groups were comparable in regard to sex, age, T-categories, tumor size, histological grade and concomitant dysplasia. The two randomization groups included 88 and 95 patients respectively. The treatment plan was followed by 66 patients (75%) in the planned cystectomy group and by 88 (92%) in the radical radiotherapy group of which 27 (28%) were treated with salvage cystectomy. The results showed a trend to a higher survival rate following the combined treatment with preoperative irradiation and cystectomy compared to radical irradiation followed by salvage cystectomy in case of residual tumor, but a statistical significant difference could not be demonstrated. The lack of difference also applied according to the actually given treatment. There was no difference in surgical complications between planned and salvage cystectomy and there were no postoperative deaths among the cystectomized patients. The type of late complications was different in the two treatment groups, but there were no major differences in the number of complications except for the fact that all male patients experienced erective impotence after cystectomy. The T-category, response to radiotherapy and frequency of lymph node metastases were found to be of prognostic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell

Comparison between short-course high-dose preoperative irradiation with immediate radical cystectomy and salvage cystectomy after full-dose irradiation.

Between 1976 and 1983, 70 patients who underwent cystectomy for transitional cell carcinoma (TCC) of the bladder were retrospectively divided into two groups: 39 patients were treated by a protocol using 2,000 rad of radiation over a period of 5 days followed by immediate cystectomy (group 1); 31 patients who failed to be cured by definitive radiotherapy of 6,000 rad were treated by salvage cystectomy (group 2). The 5-year disease-specific survival rate was not significantly different in the two groups of patients (64.5 and 65.5%). The postoperative early complication rates were similar as well (36.8% in group 1 and 35.5% in group 2). One patient of the group treated with 2,000 rad died 19 days after surgery, giving an operative mortality of 1.4%. We conclude that there is a continuing role for salvage cystectomy after irradiation failure. One-stage salvage cystectomy has a relatively low morbidity and should be performed early after failure of definitive irradiation.

Aged

[Infiltrating transitional carcinoma of the bladder (I). Comparison of 2 groups treated with preoperative radiotherapy (long-term protocol and short-term protocol) + radical cystectomy versus radical cystectomy only. Analysis of local recurrence and metastasis].

We analyze our experience in 175 patients with transitional bladder cancer for whom radical cystectomy was indicated. Patients were divided into three groups: one group was managed with radical cystectomy only and the other two with pre-operative radiotherapy: long-term approach and short-term approach. No significant differences have been observed when comparing current survival rate and disease-free intervals of all three groups. It can be deduced from our series that, by the scarce number of local recurrences observed, there is no other measure to be added to surgery directed to improve the tumour's local management. Most metastasis were diagnosed within 18 months after cystectomy. 58.4% patients presented bone dissemination. The risk of distant dissemination increases with the extent of vesical wall invasion, degree of anaplasia and presence of positive glands. The gland stage is not necessary for the metastasis to be present. Death's ratio with distant dissemination is significantly lower in the group managed Without pre-operative radiotherapy than in the others. Of the 11 patients where no tumour was observed in the cystectomy piece, 2 developed metastasis, indicating that this was already present before bladder extraction. Management of patients with infiltrating++ bladder cancer is complex, but no efforts should be spared to advise the most appropriate approach for each particular case. Chemotherapy plays an unquestionable role among the procedures we have to control, since most patients' deaths happen within two years after local-regional treatment of the primitive tumour and nearly all of them as a consequence of metastasis. Cytostatic agents are the only effective therapy for distant dissemination. We believe that every patient with a cancer extended to the perivesical fat or with dissemination to regional glands, whichever the stage, should be treated with chemotherapy after extirpation of the bladder, and starting as early as the patient's general status would allow it.

Actuarial Analysis

Contemporary cystectomy versus preoperative radiation plus cystectomy for bladder cancer.

The role of preoperative radiation therapy (RT) as an adjunct to radical cystectomy (C) was studied by reviewing 58 consecutive patients requiring bladder removal during 1980-1982 for transitional cell carcinoma (TCC). Thirty-six patients underwent RT + C; 22 had C alone. The sole reason for choosing between RT + C versus C was physician prejudice favoring one form of therapy over another. Pretreatment clinical staging was similar in both groups, slightly favoring the RT + C group with only 25 percent versus 36 percent of C patients with clinical stage exceeding B1. Pathologic stage distribution similarly favored the RT + C group slightly with only 56 percent versus 68 percent of C patients having lesions with P-stage greater than B1. Thirty-three percent of patients in the RT + C group had papillary lesions in contrast to only 27 percent in the C alone group. There was only one postoperative death in each group. Three-year minimal follow-up was available in all surviving patients. One-, two-, and three-year survival free of disease was 94 percent, 80 percent, and 70 percent, respectively, in the group treated by C alone. Similar figures for the RT + C group were 86 percent, 76 percent, and 60 percent, respectively. Projected five-year survival rates for both groups regardless of preoperative RT was over 60 percent. All but one failure in the RT + C group had 4,000 rad or more preoperative radiation. This contemporary study shows no advantage of preoperative radiation in patients requiring cystectomy for transitional cell carcinoma of the bladder.

Carcinoma, Transitional Cell

Radical cystectomy for residual of recurrent tumour after definitive radiotherapy (salvage cystectomy).

The results of salvage cystectomy for persistent or recurrent tumour following definite radiotherapy in 47 patients are reviewed. The calculated five-year survival rate was 25% for all stages, with a significantly better survival for the low pathological stages. Operative mortality was 12.8%. It was concluded that salvage cystectomy is a suitable supplement in the treatment of bladder cancer in spite of the considerable operative mortality and complication rate.

Adult

[Partial cystectomy: and alternative to radical cystectomy? Apropos of a series of 75 patients].

From a retrospective series of 75 patients, we try to determine the place of this treatment with respect to bladder urothelial cancer. Of our 75 patients the breakdown of tumours according to their stage is the following: PTA: 16 (21.3%) PT1: 12 (16%) PT2: 21 (28%) PT3 A: 15 (20%) PT3 B: 7 (9.3%) PT4: 4 (5.4%) 47 patients benefited from a complete check up of tumoural spread which is negative in any case. In 28 cases, an uretero-vesical reimplantation was necessary for carcinologic reasons. None of the patients benefited from chemotherapy and/or radiotherapy in pre or post-operative period. Mortality was 4% (3 cases) and morbidity 8% (6 cases)- Sixty two Patients were followed-up at 5 years. The results are expressed according to different carcinologic parameters. The overall rate of recurrence is 61.2% (38/62). The actuarial survival corrected at 5 years, all stages and grades included, is 53.2% (32/62). There was no recurrence in 18 patients (29%) and 29 patients preserved their bladder. The advantages of partial cystectomy are obvious: Its mortality and morbidity are weak. It also preserves the sexual function and mainly avoids resorting to urinary derivations. As a principle these indications apply to a small percentage of invasive tumours T2-T3 A located in the mobile part of the bladder that is unifocal and of small size (< 4 cms).

Actuarial Analysis

Enhancing effect of partial cystectomy on rat urinary bladder carcinogenesis.

The effects of 5% and 50% partial cystectomies on bladder tumorigenesis initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) were investigated in Wistar rats by examining the histological findings and cell proliferative activity. The incorporation of bromodeoxyuridine (BrdUrd) into the DNA synthesis phase was determined by an in-vitro labeling technique. After eight weeks of treatment with drinking water containing 0.05% BBN, 5% or 50% partial cystectomy was performed at the end of week 16, and the resected bladder was sutured with dexon or silk. There was no difference in the incidence of papillary or nodular (PN) hyperplasia between the control and partial cystectomy groups. However, the incidence of cancer in the group given partial cystectomy was much higher than that in the control. All the cancers in the control group were grade-1 superficial tumors, whereas grade-2 or invasive tumor was observed in six of 40 animals in the partial cystectomy group. The 31.0% labeling index of cancer in the partial cystectomy group was greater than the 24.1% in the control group. There was also a significant difference in the number of BrdUrd-labeled cells in PN hyperplasia between the control and partial cystectomy groups. These findings indicate that partial cystectomy enhances BBN-initiated bladder carcinogenesis and the increase in DNA synthesis found in PN hyperplasia and cancer may be associated with the induction of bladder tumors.

Animals

Histological and quantitative prognostic factors in transitional cell bladder cancer treated by cystectomy.

A cohort of 103 transitional cell bladder tumours (TCC) treated by cystectomy was followed up over 9 years. Patients treated with radiation and cystectomy had a more unfavorable prognosis than patients treated by cystectomy alone (p < 0.0001). Old patients had an unfavorable prognosis after cystectomy, whereas none of the patients under the age of 50 died of TCC after cystectomy (p = 0.027). WHO grade (p = 0.002), high mitotic rate (p = 0.012) and nodular growth pattern (p = 0.004) were signs of ominous disease outcome in univariate survival analysis. Dense inflammatory cell infiltrates in the tumour itself or around invasive tumour cells were signs of good prognosis after cystectomy (p = 0.001) in a multivariate analysis. Clinical stage or nuclear morphometric factors had no independent prognostic value after cystectomy. The results clearly show that the intrinsic malignancy of TCC and host defence mechanisms together determine the prognosis after cystectomy. The evaluation of malignant features in TCC alone is an insufficient means of predicting prognosis in invasive TCC and the analysis of host immune response should be included in the prognostic evaluation.

Age Factors

Reappraisal of the role of radical radiotherapy and salvage cystectomy in the treatment of invasive (T2/T3) bladder cancer.

One hundred and eighty-two patients with invasive (T2/T3) bladder cancer were treated by radical radiotherapy at the London Hospital between 1974 and December 1985. Cystectomy was reserved for patients whose tumours either did not respond completely to radiation or recurred later, provided they were fit for surgery and had not developed distant metastases. The overall corrected 5-year survival rate was 40%; 75 patients responded to radiation and did not relapse during the period of follow-up; 20 patients had an initial response to radiation but subsequently relapsed, with a 5-year survival rate following relapse of 20%. Of these, 11 patients had a cystectomy with a 5-year survival following relapse of 36%, whereas all 9 patients who did not have a cystectomy died within 3 years; 87 patients who did not respond to radiation had a 5-year survival rate of 18%. Of these, 22 patients underwent salvage cystectomy with a 5-year survival of 47%, whereas the 65 patients who did not have a cystectomy had a 5-year survival of 3%. These results justify a policy of radical radiotherapy and salvage cystectomy rather than elective cystectomy in the treatment of invasive bladder cancer.

Adult

Urethrectomy is harmful for preserving potency after radical cystectomy.

Twenty-three patients who underwent conventional total cystectomy were examined regarding postoperative potency. Two patients who were subjected to simple cystectomy and whose partial prostate and whole seminal vesicles were left showed full erection and normal ejaculation 1-2 months after surgery, thus giving 100% potency after simple cystectomy. In contrast, of 12 patients who underwent radical cystectomy alone, only 3 (25%) regained potency postoperatively, and the strength and duration of erection were not satisfactory for 1 of the 3 patients. Nine patients who received radical cystectomy and urethrectomy did not show signs of potency postoperatively. The sum total postoperative potency rate in the 21 patients subjected to radical cystectomy was 14.3% (3/21). The facts may indicate that urethrectomy is harmful for postoperative potency because damage of the cavernous nerves probably takes place during surgery. To avoid nerve damage, the urethra should be left intact during radical cystectomy employing the nerve-sparing technique developed by Walsh and Donker unless the posterior urethra is invaded by bladder carcinoma. In addition, it was demonstrated that pelvic irradiation might cause impotency as neither pelvic lymph node dissection nor cisplatin administration had any influence on postoperative potency.

Aged

[Clinical evaluation of total cystectomy for bladder carcinoma: a ten-year experience].

Fifty-three patients with primary bladder carcinoma underwent total cystectomy during the past 10 years. Ages ranged from 32 to 87 years old, with an average of 68.2 years. Radical total cystectomy, including systemic lymphadenectomy was performed in 22 cases, simple total cystectomy in 8 cases and salvage total cystectomy in 23 cases. An ileal conduit was made for urinary diversion in 23 cases and the other 26 cases underwent cutaneous ureterostomy. Postoperative mortality was 9.4% (5 of 53 cases) and postoperative complications were noted in 17 of the 53 cases (32.1%). The 5-year cumulative survival rate by the life table method for all the cases was 42.6%. The 5-year cumulative survival rate of radical total cystectomy cases was 67.8%, that of simple total cystectomy cases was 50.0% and that of salvage total cystectomy cases was 7.5%. A significant difference was seen between the first 2 groups and the last group. The 5-year cumulative survival rate of the patients with low stage cancer (pTis, pTa, pT1 and pT2) was 56.1% and that of the patients with high stage cancer (pT3, pT4) was 22.7%. A significant difference was observed between the two groups. The 5-year cumulative survival rate of the patients with grades G1, G2 and G3 cancer was 66.7, 45.4 and 26.7% respectively. A significant difference was seen among the three grades.

Adult

Partial cystectomy in the management of rhabdomyosarcoma of the bladder: a report from the Intergroup Rhabdomyosarcoma Study.

Among 154 children with primary vesical rhabdomyosarcoma entered in the IRS (1972 to 1986), tumor excision constituting a partial cystectomy was performed in 33. These procedures were performed in the following situations (1) as an initial operation for localized disease (22); (2) as a secondary procedure for localized disease following chemotherapy (CT) or CT/irradiation response (6); and (3) as an initial operation in the presence of disseminated abdominal disease (5). Partial cystectomy included full-thickness resection of 15% to 80% of the bladder wall. Ureters were reimplanted or revised in two patients. The 33 patients undergoing partial cystectomy were in the following clinical groups: I, total excision (10); II, gross excision with "microscopic residual" or positive nodes (8); III, subtotal excision (10); and IV, tumor dissemination (5). Patients in clinical groups I and II received vincristine and actinomycin-D (VA) or VA + cyclophosphamide (VAC) +/- adriamycin (ADR). Patients in groups III and IV received the same agents +/- cisplatin. Irradiation (2,000 to 5,000 cGy) was administered to 18 patients (55%) in groups II to IV. Six relapses occurred among 28 patients with localized disease, and one among five patients with dissemination; all resulting in progressive disease and/or death. Estimated 3-year survival following partial cystectomy (79%) is similar to that for all patients with primary bladder tumors (78%). In contrast with the total group, in which the majority of survivors have eventually required total cystectomy; 25 of 26 survivors of partial cystectomy have functional bladders from 146 to 686 weeks (median, 356 weeks) from study entry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Transitional cell carcinoma of the urethra in men following cystectomy for bladder cancer: multivariate analysis for risk factors.

Multicentric development of transitional cell carcinoma in the urinary tract is well recognized. Of 169 male patients who underwent cystectomy for bladder cancer 18 (10.6%) demonstrated urethral cancer (all within 5 years after cystectomy). The risk factors involved in transitional cell carcinoma in regard to the occurrence of urethral cancer after cystectomy were examined by multivariate analysis. Characteristic patterns of bladder cancer in the cystectomy specimens were expressed by the grade, stage, number, size, location and gross pattern of the tumors. Significant risk factors in bladder cancer relating to the development of cancer in the retained urethra were papillary cancer, multiple cancers, and tumors in the bladder neck, prostatic urethra and prostatic gland. Among 19 patients with concomitant carcinoma in situ and/or multiple papillary tumors in the bladder who underwent simultaneous prophylactic urethrectomy with cystectomy in the same observed period 17 (89%) had no lesion in the resected urethra. The results of the multivariate analysis will be useful to avoid unnecessary prophylactic urethrectomy at cystectomy. However, further analysis and consideration of possible mechanisms of the secondary urethral cancer will be necessary to explain the discrepancy posed in the latter study involving 19 patients.

Adult

Transitional cell carcinoma of the bladder: patterns of recurrence after cystectomy as determined by CT.

CT scans have been recommended for examination of patients at risk for recurrent transitional cell carcinoma after cystectomy. For CT to be useful in this regard, the location and type of recurrences must be known, so that appropriate scans can be made. Therefore, we retrospectively studied CT scans in 27 postcystectomy patients with recurrent transitional cell carcinoma of the bladder to identify the type and location of the recurrent disease. Recurrence was documented by biopsy in 18 patients and by progression of disease shown on serial CT scans in nine patients. All 27 patients had pelvic CT, and 23 had concomitant abdominal CT. Tumor recurred at the cystectomy site in 10 (37%) of 27 patients, pelvic adenopathy was present in 18 (67%) of 27 patients, and retroperitoneal adenopathy was present in 13 (57%) of 23 patients. Tumor recurrence at the cystectomy site was associated with pelvic adenopathy in seven of 10 patients, and the cystectomy site was the solitary site of disease in the remaining three patients. Conversely, in 11 of 18 patients with pelvic adenopathy no recurrence was seen at the cystectomy site. Combined retroperitoneal and pelvic adenopathy was identified in 11 of 23 patients, but two patients had retroperitoneal lymphadenopathy as their only site of recurrence. Hepatic metastases were seen in seven (30%) of 23 patients; six of these seven patients had metastases elsewhere. In four of five patients in whom underestimation of recurrent disease occurred, the deep pelvis and/or deep perineal space were involved. Our results show that the pelvis is the most common site for recurrence. Cystectomy site or retroperitoneal nodal recurrences are usually accompanied by pelvic adenopathy, but the converse is not as common. Our findings of deep perineal and isolated abdominal recurrences indicate that proper protocol for CT follow-up of the postcystectomy patient should include abdominal scans and scans through the perineum.

Aged