Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.

BACKGROUND: Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment. This phase III, randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen substudy (SOLE-EST) analyzed the levels of estrogen during the interruption of treatment. PATIENTS AND METHODS: SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant ET. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day for 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all of year 5). RESULTS: Intention-to-treat population included 4851 women in SOLE (n = 2425 in the intermittent and n = 2426 in the continuous letrozole groups) and 103 women in SOLE-EST (n = 78 in the intermittent and n = 25 in the continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival (DFS) was 81.4% in the intermittent group and 81.5% in the continuous group (hazard ratio: 1.03, 95% confidence interval: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment. CONCLUSIONS: Extended adjuvant ET by intermittent administration of letrozole did not improve DFS compared with continuous use, despite the recovery of circulating estrogen levels. The similar DFS coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.

Docetaxel and cisplatin in metastatic urothelial cancer: a phase II study.

PURPOSE: Docetaxel and cisplatin has documented single-agent activity and different toxicity profiles in patients with metastatic urothelial cancer. We performed a phase II study in which docetaxel was combined with cisplatin to evaluate response rate, toxicity, and survival. PATIENTS AND METHODS: Eligibility criteria included performance status (World Health Organization [WHO]) less than 3; normal bone marrow, liver, and renal function; and no concurrent malignancy or symptomatic peripheral neuropathy. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Paris, France) 75 mg/m2 was combined with cisplatin 75 mg/m2 every third week. Patients received premedication with prednisolone and clemastine. RESULTS: A total of 25 patients were assessable for response and toxicity. Median age was 64 years; five patients had locoregional disease only and 20 had metastatic disease. Response was achieved in 15 patients (60%; 95% confidence interval [CI], 39% to 79%), including seven patients (26%) who achieved a complete response. Overall median survival time was 13.6 months (range, 1.5 to 26.4+). The most frequent toxicity was nausea and vomiting (80% of patients). Neutropenia grade 3 or 4 was observed in 56% of patients, but only one had febrile neutropenia. Mucositis and diarrhea were encountered in 13% of cycles, mostly grade 1 or 2. Peripheral neuropathy and skin changes grade 1 and 2 were observed in 76% and 36%, respectively. Fluid retention and hypersensitivity reactions were infrequent and mild. CONCLUSION: The combination of docetaxel and cisplatin is effective and feasible in patients with metastatic urothelial cancer with a manageable safety profile.

Serum YKL-40: a new potential marker of prognosis and location of metastases of patients with recurrent breast cancer.

YKL-40 is a recently discovered glycoprotein which is related in amino acid sequence to the chitinase protein family, but has no chitinase activity. Although the function of YKL-40 is presently unknown, the pattern of its expression by some tissues suggests that YKL-40 could function in tissue remodelling. The diagnostic features and relation to survival of serum YKL-40 have not been examined previously in human malignancies. In the present study YKL-40 was measured in serum obtained from 60 patients at the time that breast cancer recurrence was suspected. The median serum YKL-40 in patients with visceral or bone metastases was 328 and 157 micrograms/l, respectively and significantly higher compared to controls (99 micrograms/l, P < 0.001). Kaplan-Meier survival curves demonstrated that survival rates after 18 months were 24% for patients with high serum YKL-40 (> 207 micrograms/l = the 95 percentile of controls) and 60% for patients with normal serum YKL-40. The significance of the difference between the shorter survival of patients with high serum YKL-40 and the longer survival of patients with normal serum YKL-40 was high (P < 0.0009). When evaluated with other prognostic factors of survival after recurrence of breast cancer, serum YKL-40 and serum lactate dehydrogenase (LDH) were the most significant independent factors. The results indicate that determination of serum YKL-40 can be used as a prognostic marker related to the extent of disease and survival of patients with recurrence of breast cancer. In addition, the serum YKL-40 level may be of value in the follow-up of patients with breast cancer and in evaluating potential metastatic spread.

Tamoxifen in high-risk premenopausal women with primary breast cancer receiving adjuvant chemotherapy. Report from the Danish Breast Cancer co-operative Group DBCG 82B Trial.

Following modified radical mastectomy, pre- and perimenopausal (amenorrhoea for < 5 years) patients with stage II or III breast cancer received CMF (cyclophosphamide 600, methotrexate 40, 5-fluorouracil 600 mg/m2 intravenously (i.v.) every 4 weeks, 9 cycles). The effect on recurrence-free survival (RFS) and overall survival (OS) of the addition of adjuvant tamoxifen (TAM) to adjuvant chemotherapy was examined by randomisation either to no additional treatment (n = 314), or concurrently TAM 30 mg daily for 1 year (n = 320). 40% had positive, 12% negative and 48% unknown receptor status. One year after surgery 21% versus 35% (CMF + TAM versus CMF) were still menstruating (P < 0.01). With a median follow-up of 12.2 years there was no difference in RFS (10-year RFS 34% versus 35%, P = 0.81) or OS (45% versus 46%, P = 0.73). In a Cox proportional hazards model, tumour size, number of metastatic lymph nodes, frequency of metastatic nodes in relation to total number of nodes removed, degree of anaplasia, age, and menostasia within the first year after operation were significant independent prognostic factors for RFS, and the same factors except age for OS. No significant interactions with TAM were seen. Thus, in this group of pre- and perimenopausal high-risk early breast cancer patients with heterogeneous receptor status given CMF i.v., concurrent TAM for 1 year did not improve the outcome. These results do not exclude that receptor positive patients may benefit from adjuvant TAM for longer periods given sequentially to chemotherapy.

Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.

CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37 (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX, and the major toxicity with CAELYX was to the skin. Palmar-plantar erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%) patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non-haematological grade 3 and 4 toxicities were rare. Confirmed responses were observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%); with the best response being stable disease (NC) in 16 and 18 patients, respectively. The reason for the low response rate is unknown, but it may be due partly to a high proportion of gastrointestinal stromal tumours. In conclusion, CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity profile and should be considered for further investigation in combination with other agents such as ifosfamide.

Treatment outcome following radiotherapy in elderly patients with bladder cancer.

BACKGROUND AND PURPOSE: The optimal treatment of elderly patients with bladder cancer is not established. This study aimed to evaluate prognostic variables for survival and morbidity, which may be important for treatment strategy. MATERIAL AND METHODS: The medical records of 94 patients aged > or = 75 years receiving curatively intended radiotherapy for bladder cancer were reviewed retrospectively. RESULTS: Median age was 78 years (range 75-93 years). Fifty patients had T1-2 tumors, and 42 patients had T3-4 tumors. The total planned dose was 57.6-62.6 Gy in 24-30 fractions in 6 weeks. In 76 patients, a 2 week rest period was planned after 16 fractions (split course). Half of the patients were hospitalized during or after the treatment because of gastrointestinal or urogenital side effects. Median survival was 13.9 months (range 0.6-150.0 + months), 29% survived for 2 years and 7% survived for 5 years. Patients aged > 78 years survived for a shorter period than patients aged 75-78 years (13.4 versus 16.1 months). Univariate survival analysis revealed that low stage (T1-2), good performance status (PS < or = 1), split course treatment, no treatment interruption due to side effects, and no hospitalization during treatment were associated with long survival. In multivariate analyses, T-stage, split course treatment, and performance status were independent prognostic factors. CONCLUSION: The results confirm that curative intended radiotherapy is feasible in elderly patients, but patients with stage T3-4 and PS > 1 have a short survival. These patients should be offered palliative treatment.

Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method.

The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine-induced specific immunity in breast cancer patients. Peripheral blood was collected from five breast cancer patients at serial time points in connection with treatment and in a follow-up period of 1 year. The frequencies of CD8+ and CD4+ T cells responsive to cytomegalovirus (CMV), varicella zoster virus (VZV), and tetanus in antigen-activated whole blood were determined by flow cytometric analysis of CD69, TNF alpha, IFN gamma and IL-4 expression. Mononuclear cells were labelled with PKH26 dye and the CMV, VZV, and tetanus toxoid-specific proliferation of T cell subpopulations was analysed by flow cytometry. In none of the patients did the treatment result in loss of overall T cell reactivity for any of the antigens. Prior to chemotherapy 5/5 patients possessed TNF alpha expressing T cells specific for CMV, 4/5 for VZV, and 3/5 for tetanus. One year after stem cell transplantation all patients possessed TNF alpha expressing T cells specific for CMV, VZV and tetanus. The highest percentages of cytokine-responding T cells were seen after stimulation with CMV antigen. In general, the lowest reactivity (close to zero) was measured in G-CSF-mobilised blood at the time of leukapheresis. In spite of a continuously reduced CD4 to CD8 ratio after transplantation, recovery of CD4+ T cells usually occurred prior to CD8+ recovery and often to a higher level. The study demonstrates that natural as well as vaccine-induced specific immunity established prior to HD can be regained after stem cell transplantation. These data indicate that introduction of a preventive cancer vaccination in combination with intensive chemotherapy may be a realistic treatment option.

Loss of heterozygosity at 1p, 8p, 10p, 13q, and 17p in advanced urothelial cancer and lack of relation to chemotherapy response and outcome.

Studies of urothelial tumors have identified structural abnormalities in a number of chromosomes. This study aimed to identify specific genetic changes of patients with advanced urothelial cancers, and relate these changes to increased chemotherapy sensitivity or good prognosis. We screened 56 muscle-invasive bladder cancer tumors for loss of heterozygosity (LOH) at chromosome 1p, 8p, 10p, 13q, and 17p with PCR using 6 microsatellite markers. All patients had recurrent locally advanced or metastatic disease. DNA was extracted after microdissection of the primary tumor and normal tissue from paraffin-embedded specimens. The PCR products were electrophoresed in an ABI Prism 377 DNA sequencer and the alleles from tumor DNA and normal tissue DNA were analyzed using the GeneScan program. The LOH findings were correlated with response to chemotherapy and survival. Allelic loss of specific markers was present in 26-50% of the informative tumors. The most frequent LOH was observed at 17p, supporting the notion that this region may contain genes of importance to urothelial cancer progression. The overall rate of response to chemotherapy was 48%, and ranged from 40% to 56% according to specific LOH changes. The median survival of all patients from start of chemotherapy was 5.8 months and ranged from 5.3 to 7.9 months for patients with specific LOH changes. Response and survival of patients with no lost markers was the same size, compared to patients with one, two, or more lost markers. Specific genetic changes were detected in a significant number of tumors from patients with advanced urothelial cancer. These changes were not predictive of response to chemotherapy or of the duration of survival.

Predictive factors of response to cisplatin-based chemotherapy and the relation of response to survival in patients with metastatic urothelial cancer.

PURPOSE: To identify pretreatment variables predicting overall and complete response to cisplatin-based chemotherapy for metastatic urothelial cancer, and to study the relation between response and the duration of survival. PATIENTS AND METHODS: A total of 119 evaluable patients with recurrent locally advanced or metastatic urothelial cancer received cisplatin-based combination chemotherapy in four consecutive phase II studies from 1987 to 1997. The relationship of pretreatment variables and response was evaluated with logistic regression, and prognostic factors for survival were analyzed with Cox's multivariate model. RESULTS: Response was achieved in 49% of the patients with a complete response rate of 15%. Good performance status and absence of bone metastases were independently predictive of overall response. Good performance status and normal hemoglobin were independently predictive of complete response. Median survival was 8.9 months. Performance status, alkaline phosphatase, s-creatinine, liver and bone metastases were independent prognostic factors for survival. Median survival was 12.4 months in responding patients and 6.3 in nonresponding patients. Response to chemotherapy was included in the multivariate model and was the strongest prognostic factor for survival. CONCLUSION: The presence of bone metastases, low hemoglobin or poor performance status predicts decreased chance of response to chemotherapy. Response to chemotherapy is an independent prognostic factor for prolonged survival in patients with metastatic urothelial cancer.

Assessment of functional status in patients with invasive carcinoma of the urothelial tract.

Performance status score is an important prognostic factor for response and survival for patients entering clinical trials. Evaluation of the functional status of the patients should be considered when retrospective studies on prognostic factors are performed. However, the methodologic problems of evaluating performance status retrospectively are unknown. The aim of this study was to evaluate the reliability and validity of retrospective assessment of performance status based on information from patient records. The level of performance status was analyzed in relation to duration of survival after primary or recurrent carcinoma of the urinary tract. The records of 149 patients with primary urothelial carcinoma and 53 patients with recurrent disease were blindly scored twice by two investigators according to the World Health Organization (WHO) performance status scale. The median time of observation was 109 months (range 3-219); 13 patients were alive at the time of follow-up. When scores of the performance were compared for patients separated in two groups, good performance (WHO scores 0 and 1) versus poor performance status (score >1), the intraobserver overall agreement for the assessments varied from 82% to 89%, whereas the interobserver agreement varied from 76% to 86%. The range of the intra- and interobserver kappa coefficients (95% CI) were 63% to 72% (52% to 83%) and 49% to 68% (40% to 79%), respectively. All four assessments were significantly related to survival (p < 10(-4)). Multivariable proportional hazard regression analysis showed that gender, platelet count, level of liver enzymes, and each of the four assessments of performance status (analyzed in four separate statistical models) were significant prognostic factors. Retrospective scoring of performance status is a reproducible and reliable tool that provides additional prognostic information. Optimal retrospective evaluation of the simultaneous effect of multiple prognostic factors should therefore include an assessment of the functional status of the patient.

The functional and psychosocial status of patients with disseminated bladder cancer.

This study describes self-reported functional and psychological status of patients using The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and relates this to the prognosis. Patients with incurable locally advanced or metastatic transitional cell cancer of the urothelial tract were prospectively included in a study of self-reported functional and psychosocial status. The study included 25 patients; 19 patients completed one or more Quality of Life Questionnaires. The median survival was 5.2 months, and there was a significant relation between functional, emotional, and social status and survival. The self-assessment of functional status was a better prognostic factor for survival than performance status evaluated by the clinician. The value of the global quality of life scale did not relate to survival after recurrence. Functional, emotional, and quality of life scales declined during the progression of the disease. The study suggests that evaluation with self-reporting questionnaires may provide the physician with useful information, and it may aid in making treatment decisions in patients with metastatic bladder cancer.

Pattern of metastases in human breast carcinoma in relation to estrogen receptor status.

The distribution of metastases at the first recurrence of breast cancer was studied in 57 estrogen receptor (ER) positive and in 23 ER negative patients, who constituted a subset of 460 patients with operable breast cancer. The pattern of metastases with respect to localization of metastases and the dominant site of first recurrence was similar in patients with ER positive and ER negative tumours. The recurrence-free survival (RFS) and the overall survival were associated with the ER status in the 460 patients. ER positive patients had both a significantly longer RFS (p = 0.0024) and survival (p = 0.0001) compared to ER negative patients. Survival after recurrence was prolonged in patients with soft tissue recurrences only, and the proportion of dead patients was highest in receptor negative patients with metastases to bone and viscera. In conclusion, we could not demonstrate that ER positive and negative tumours have a propensity for recurrence at specific sites.

Lack of effect from mitomycin c plus 5-fluorouracil in platin-resistant ovarian cancer: a phase II study.

Sixteen patients with advanced ovarian cancer were included in a phase II study with mitomycin c (MMC) plus 5-fluorouracil (5-FU). All patients had previously received platin-based combination therapy, but were resistant to this treatment. A MMC 10 mg m-2 intravenous (iv) bolus was given on day 1 every 6 weeks, and 5-FU 1000 mg m-2 was given iv on days 1-3 every 3 weeks, as a continuous infusion over 72 h. Fifteen patients were evaluable for response. There were no responders, neither partial nor complete. The median survival was 6 months. The toxicity was primarily bone marrow suppression. The treatment was generally well tolerated. No patients had grade 4 toxicity and only five had grade 3 hematologic toxicity. In conclusion, we find the present regimen to be ineffective in the treatment of platin-resistant ovarian cancer.

Immunohistochemical detection of estrogen receptors in paraffin sections from primary and metastatic breast cancer.

With the availability of monoclonal antibodies against the estrogen receptor (ER) it is possible to demonstrate the presence of ER immunohistochemically. Some of the antibodies are claimed to be reactive in formalin fixed, paraffin embedded tissue. We have evaluated the reactivity of one of these antibodies, D75 and found an acceptable reaction in routinely formalin fixed, paraffin embedded tissue. The antibody was applied to both primary and secondary tumors from a group of patients with recurrent breast cancer. The metastatic lesions consisted of lymph node metastases, bone marrow metastases, and liver metastases. While 41% of the primary tumors were ER-positive, this was only the case with 35%, 20%, and 17% of the lymph node, bone marrow, and liver metastases, respectively. The discordance between the ER-status of the primary tumor and the distant metastasis was 41% in cases of bone marrow metastases, and 44% in liver metastases. In most cases the shift was from an ER-positive primary tumor to an ER-negative metastasis. The results support the hypothesis that ER-negative tumor cells are probably more aggressive with a larger metastatic potential than the higher differentiated, ER-positive tumor cells.

Survival and pattern of failure following locoregional recurrence of breast cancer.

This study analyzed prognostic factors at primary diagnosis and at first recurrence for impact on survival after isolated locoregional failure. The aims were: (1) assessment of prognostic factors for time to second locoregional failure, distant failure, and survival in isolated locoregional recurrence of breast cancer after mastectomy; and (2) investigation of the impact of a second locoregional failure on dissemination and survival. Between 1983 and 1985, 99 patients who had undergone mastectomy and then developed isolated local and/or regional recurrences, were treated with radical excision and radiotherapy; none of these patients had distant metastases. Survival and the times to second local failure and distant metastasis were analyzed according to potential prognostic factors. The median follow-up was 123 months; 38 patients were still alive. Median survival was 89 months and the 10-year survival rate was 38%, with no difference between local and regional recurrences. A total of 43 patients developed a second locoregional recurrence after a median of 73 months; primary tumour size and initial node status were significant independent prognostic factors. The annual hazard rates for recurrence were similar for patients developing local failure or systemic recurrence. The 10-year rate of dissemination was 49% for patients with locoregional control, compared with 51% for patients who had a second locoregional recurrence. The prognostic factors for survival were node status at mastectomy and haemoglobin level at first recurrence. The development of a second locoregional recurrence was not associated with an increased risk of dissemination or reduced survival. Differences in prognostic factors for locoregional control and distant metastases suggest that these recurrences represent different biological entities that require different treatment strategies. However, as the achievement of locoregional control had no influence on prognosis, the use of systemic adjuvant therapy may be warranted in a subset of these patients.

[Routine check-ups of patients with breast cancer. Significance of the referral pattern for survival after recurrence]. / Rutinekontrol af patienter med cancer mammae. Henvisningsmønsterets betydning for overlevelse efter recidiv.

The clinical course of recurrent breast cancer was compared in 117 patients with recurrence diagnosed at routine follow-up visits and 100 patients with recurrence detected in the interval between two scheduled follow-up visits. The interval recurrences were diagnosed after self-appointments (37 cases), after referral by general practitioners (31 cases) or other departments (32 cases). The two groups of patients were comparable with respect to age, menopausal status, initial stage of disease, and the type of adjuvant systemic therapy. The interval group of patients had a longer recurrence-free interval and also more symptoms than the routine group. The anatomical distribution of metastases was comparable in the two groups. The interval group of patients had a shorter survival after recurrence compared to the routine group (median 16 versus 25 months, p = 0.07). The survival from initial diagnosis was comparable in the two groups (48 versus 58 months, p = 0.67). Using multivariate Cox regression analysis, the influence of interval as compared with routine recurrences was evaluated in relationship to other prognostic variables (initial stage, recurrence-free interval, presence of visceral metastases, number of metastatic sites). In this model, the stage of disease, the recurrence-free interval, and presence of visceral metastases were the only significant independent prognostic factors.

[The significance of prognostic factors on the occurrence of metastases from breast cancer to various localizations]. / Prognostiske faktorers indflydelse på forekomsten af metastaser i forskellige lokalisationer ved cancer mammae.

The aim of the study was to identify and compare risk factors for development of metastases from breast cancer at specific anatomical sites. The sites were grouped into ten categories, simultaneous occurrences at several sites being common. The influence of various risk factors for recurrence at one specific site can be modelled by well-established survival analysis techniques such as the Cox regression model. Recently, a generalization has been proposed that allows for joint occurrences at more than one site. The prognostic influences of various risk factors on recurrence at different sites may be compared using these models. Both methods were applied to data from the Danish Breast Cancer Cooperative Group on recurrence after breast cancer; the risk factors examined were degree of anaplasia, number of positive lymph nodes, site of primary tumour, skin or deep fascial invasion, age of the patient and adjuvant treatment regimens. Adjuvant therapy had the same effect on recurrence at all sites. For chemotherapy, this effect was marginally significantly positive. The number of positive lymph nodes was associated with an increased risk of metastases at all sites except the brain, where an opposing trend was found. The degree of anaplasia was associated with a somewhat increased risk of metastases at all sites, again the brain was an exception, here the effect of degree of anaplasia was significantly more pronounced. Application of the new types of models resulted in fewer differences between the relative influence of the prognostic factors than are implied by the use of the traditional regression models.

[Systemic chemotherapy in bladder cancer]. / Systemisk kemoterapi ved blaerecancer.

This review reports the results of chemotherapy in advanced bladder cancer with emphasis on the latest studies concerning combination chemotherapy containing cisplatin and methotrexate. The main conclusion is, that chemotherapy has a tumor-reducing effect on both metastatic disease and local/regional recurrences, but it remains to be proven whether overall long-term survival is affected. Among patients who respond to chemotherapy, the survival seems to be prolonged, 10-15% of these patients achieving more than two years of disease-free survival. The most effective treatment regimes contain cisplatin and methotrexate. It is assumed that many patients with muscle-invasive bladder tumors have microscopic dissemination of the disease at the time of diagnosis, and chemotherapy has been given to these patients as primary treatment alone or as an adjuvant to cystectomy or radiotherapy. These studies have not been able to show any benefit in terms of prolonged survival of patients receiving chemotherapy. The results of on-going randomised studies are still awaited. It is concluded that chemotherapy to patients with both primary and metastatic bladder cancer is still an experimental treatment, which should only be used in the context of investigational studies.

[The value of bone marrow scintigraphy in patients with recurrent breast cancer]. / Vaerdien af knoglemarvsskintigrafi hos patienter med recidiverende cancer mammae.

Attempts were made to assess the value of various methods of demonstration of bone metastases in patients with recurrence of cancer of the breast. A material of 123 patients with suspected or verified recurrence of cancer of the breast was submitted to a programme of investigation consisting of conventional X-ray survey of the axial skeleton and thorax, bone tissue scintigraphy, bone marrow scintigraphy, bone biopsy and aspiration of marrow and blood status including serum alkaline phosphatase. 54% and 29% of the patients had bone, metastases as assessed radiographically and by biopsy, respectively. In patients with radiographically demonstrated bone metastases, the predictive value of positive (PV-pos) whole-body scintigraphy was 79%. The findings on bone tissue scintigraphy and bone marrow scintigraphy were in agreement with the radiographic findings in 78% and 72%, respectively, and with the biopsy findings in 71% and 74%, respectively, of the cases. All of the cases of metastases verified by biopsy were identified also by radiographic examination and by bone tissue scintigraphy. The predictive value of negative bone tissue scintigraphy (PV-neg) was 76% and of bone marrow scintigraphy 65%. With biopsy as the final proof, bone tissue scintigraphy, bone marrow scintigraphy and radiography were found to have PV-pos values of 96%, 89% and 95%, respectively and PV-neg values of approximately 50% for all three forms of examination. Bone marrow scintigraphy has thus no diagnostic advantages as compared with bone tissue scintigraphy.(ABSTRACT TRUNCATED AT 250 WORDS)