Age-related Differences in Recall of Information and Handling of Chemotherapy-related Side Effects in Cancer Patients: The ReCap Study.

BACKGROUND: To prevent severe toxicity and hospital admissions, adequate management and recall of information about side effects are crucial and health literacy plays an important role. If age-related factors impact recall of given information and handling of side effects, revised ways to give information are required. PATIENTS AND METHODS: We undertook a questionnaire-based survey among 188 newly diagnosed patients with pancreatic cancer or colorectal cancer and chemo-naive patients with prostate cancer treated with adjuvant or first-line palliative chemotherapy comprising satisfaction with given information, recall of potential side effects, and handling of hypothetical side effect scenarios. We evaluated the association between baseline characteristics, ie, age, frailty (G8 score), comorbidity (Charlson Comorbidity Index), cognitive function (Mini-Cog), satisfaction, recall of information, and handling of side effects. RESULTS: Reduced ability to recall information about several side effects (eg, chest pain) was associated with older age (odds ratio adjusted for cancer [aOR] 0.94 [95% CI, 0.88-0.98]) and poor cognitive screening (aOR 0.56 [95% CI, 0.33-0.91]). Insufficient or dangerous handling of side effects was associated with older age (aOR 0.96 (95% CI, 0.92-0.99)) and cognitive impairment (aOR 0.70 [95% CI, 0.50-0.95]). CONCLUSION: Older age and poor cognitive screening may impact patients' ability to understand and adequately handle chemotherapy-related side effects. Cognitive screening and focus on individual ways to give information including assessment of recall and handling are needed.

A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy.

BACKGROUND: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. PATIENTS AND METHODS: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use. Quality of life was measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life Instrument (EQ-5D). Adverse events were recorded. RESULTS: A total of 219 patients were screened and 144 patients randomized. The median duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not reached because only 14 deaths occurred by the cut-off date. No statistically significant differences between treatment arms were noted for symptomatic PFS, PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). CONCLUSIONS: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod therapy significantly reduced the risk of rPFS by 40%. CLINICALTRIALS: gov identifier NCT01732549.

Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer.

PURPOSE: To compare long-term survival in patients with locally advanced and metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine plus cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND METHODS: Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall survival time and progression-free survival. RESULTS: Four hundred and five patients were randomized, 203 to the GC arm and 202 to the MVAC arm. At the time of this analysis, 347 patients have died (GC 176, MVAC 171). Overall survival was similar in both arms (HR 1.09; 95% confidence interval [CI] 0.88-1.34, P = 0.66) with a median survival of 14.0 months (95% CI 12.3-15.5 months) in the GC, and 15.2 months (95% CI 13.2-17.3 months) in the MVAC arm. The median progression-free survival was 7.7 months with GC (95% CI 6.8-8.8) and 8.3 months with MVAC (95% CI 7.3-9.7) with a HR of 1.09 (95% CI 0.89-1.34). Significant prognostic factors favoring overall survival included performance status (>70), TNM staging (M0 vs. M1), low/normal alkaline phosphatase expression, number of sites of disease <3, and the absence of visceral metastasis. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. CONCLUSIONS: Long-term overall and progression-free survival following treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced and metastatic transitional-cell carcinoma (TCC).

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.

A phase II study of cisplatin plus methotrexate with folinic acid rescue in metastatic or locally recurrent transitional cell carcinoma of the urothelium.

34 patients with metastatic or recurrent transitional cell carcinoma (TCC) of the urothelium were treated with cisplatin 100 mg/m2 plus methotrexate 250 mg/m2 with folinic acid rescue every 3 weeks. A response rate of 55% was achieved with two complete and 15 partial responses in 31 evaluable patients. The overall median survival was 7 months, 9 months for responding and 4 months for non-responding patients. Toxicity was generally moderate. However, 1 patient with previous infectious problems died of neutropenic sepsis. Overall, 83% of the scheduled doses of cisplatin and 96% of the scheduled doses of methotrexate were given. In conclusion, this schedule of the combination of cisplatin and methotrexate did not improve response rate or survival compared with previous studies of this two-drug combination.

Radiotherapy in bladder cancer.

In the present review, we have evaluated the outcome of radiotherapy in patients with bladder cancer. The exact value of radical radiotherapy is difficult to establish because changes in treatment techniques and selection of patients have biased the results. The 5-year survival rates are reported to be 35-71% in T1 tumors, 27-59% in T2 tumors, 10-38% in T3 tumors and 0-16% in T4 tumors. Several other factors, like performance status and hemoglobin level, are important for the outcome. Morbidity of radical radiotherapy depends on several treatment and patient related factors, but 50-75% experience acute intestinal or urological symptoms and 10-20% may develop severe late toxicity, depending on the kind of registration. The importance of field size or overall treatment time cannot be established from available data. Hyperfractionation with dose escalation has proven effective in one study. Preoperative radiotherapy with cystectomy has not proven better than cystectomy alone or better than radiotherapy alone. The addition of systemic chemotherapy has increased disease-free survival, but has not significantly reduced the rate of distant metastases or improved overall survival. Presently, the standard radiation regimen is a conventional dose and fractionation schedule to a total dose of 60-66 Gy with a three- or four-field technique covering the bladder and tumor. The efficacy of additional irradiation of regional lymph nodes is questionable. New treatment possibilities with advanced techniques of radiotherapy, hyperfractionation and dose escalation and/or the addition of systemic chemotherapy may improve outcome. These options should be further explored in clinical trials.

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.

Melanotic neuroectodermal tumour as a predominant component of an immature testicular teratoma. Case report with immunohistochemical investigations.

A case of melanotic neuroectodermal tumour (MNT), or so-called retinal anlage tumour, as a predominant component of an immature testicular teratoma is presented. The patient was a 17-year-old man who furthermore had a mature mediastinal teratoma. The MNT was composed mainly of two cell types: small immature neuroblast-like cells and large columnar or cuboidal epithelial-like cells with or without melanin granules. The tumour cells were arranged in solid formations, nests, cords, alveolar and pseudoglandular structures with cleft-like or glomeruloid-like spaces. Myogenic differentiation was found in minor foci. Immunohistochemistry showed both neuroepithelial and mesenchymal features with positive staining reaction for neuron-specific enolase (NSE), S-100 protein (S-100), melanoma antigen (HMB45), cytokeratin and vimentin. Vimentin, desmin and actin were present in the myoid cells. To the best of our knowledge this is the first reported case of MNT originating in the testis. As this tumour component occurred in an immature teratoma, neuroectodermal differentiation of germ cell origin is considered most likely.

p53 nuclear immunoreactivity as a predictor of response and outcome following chemotherapy for metastatic bladder cancer.

p53 nuclear immunoreactivity was determined in primary bladder tumours from 50 patients who developed metastatic bladder cancer. We investigated the relationship between p53 nuclear immunoreactivity and the response and outcome following chemotherapy. p53 nuclear accumulation was detected in 48% of the primary tumours using the PAb1801 antibody in archival paraffin-embedded tissue sections. All patients received platinum-based combination chemotherapy including methotrexate for metastatic disease. The response to chemotherapy did not relate to the prevalence of p53 nuclear overexpression: 50% of the patients expressing p53 nuclear reactivity achieved a response compared to 27% of those without p53 expression (P = 0.14); overall, 38% of the patients responded. The median survival after chemotherapy was 5.9 months; 8.4 months for patients with p53 nuclear reactivity compared to 5.2 months for those without (P = 0.38). Multivariate analysis showed that performance status but not p53 nuclear status was an independent prognostic factor for survival following chemotherapy. The results indicate that patients with p53 nuclear immunoreactivity in the primary bladder tumour do not have a lower response rate or poorer outcome following chemotherapy for metastatic disease than do patients without p53 nuclear reactivity.

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.

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.

[Repeated irradiation of cancer patients]. / Gentagelse af strålebehandling hos cancerpatienter.

Radiotherapy of a recurrent tumour in a site previously irradiated with a full course of radiotherapy is seldom feasible due to extensive toxicity of the cumulated dose. Curative reirradiation may be possible for very selected patients with head and neck cancer and gynaecological tumour. Patients with long recurrence-free intervals and small localized tumours are most likely to benefit from the treatment. Palliative reirradiation of patients with metastatic disease offers good symptom control in the majority of patients with recurrent symptoms from bone metastases. Some patients with brain metastases, spinal cord compression and symptoms from lung tumours may benefit from reirradiation. The general condition of the patient and the effect of the first treatment influence the effect of the second treatment. The side effects of reirradiation are not well documented. It is not possible to give general guidelines for reirradiation. Every reirradiation has to be individualized with respect to diagnosis, specifications of prior treatment, symptoms and prognosis.

[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.

Pattern of dissemination and survival following isolated locoregional recurrence of breast cancer. A prospective study with more than 10 years of follow up.

PURPOSES: The study evaluated prognostic factors for dissemination and survival in patients with local or regional recurrence of breast cancer. Furthermore, the aim was to define subgroups of patients at different risk of developing metastases in specific anatomical sites. PATIENTS AND METHODS: The study included 140 patients with isolated local or regional node recurrence, who entered a prospective study for staging of patients with first recurrence of breast cancer in the period 1983-85. The primary treatment was a simple mastectomy; node positive patients received adjuvant radiotherapy and chemotherapy or tamoxifen. If possible, the locoregional recurrence was treated with surgery and/or radiotherapy, otherwise by systemic therapy. RESULTS: Median follow up was 10.4 years; 78 patients developed distant metastases (soft tissue, 32%; bone, 45%; viscera 40%). Median time to dissemination was 4.4 years, and the ten year dissemination rate was 72%. Median time to dissemination was 3.7 years for patients with recurrence in the regional nodes compared to 6.5 years for patients with chest wall recurrence only, p = 0.05. No specific time sequence (temporal pattern) was observed in the anatomical distribution of metastases, and the anatomical site of recurrence could not be predicted by any of the prognostic factors. At follow up, 93 patients had died. The median survival was 5.6 years and 30% were alive after 10 years. Forty-three of the 99 patients who received local therapy only did not develop metastases. Fifteen of these patients died without evidence of metastatic disease while 28 patients were still alive without distant recurrence after a median follow up time of 9.3 years (range, 6.5-11.9 years). Level of LDH and the number of positive regional nodes (NPOS) at primary diagnosis were significant independent prognostic factors for survival after recurrence. CONCLUSIONS: Approximately one third of the patients receiving local treatment only, were alive and without distant metastases up to ten years after locoregional recurrence, indicating that there is a subset of patients which may be long term survivors after local treatment only (surgery or radiotherapy). The duration of survival can be estimated by LDH and NPOS, but the model needs validation in a separate data set before clinical use.

Metastatic urothelial cancer: evaluation of prognostic factors and change in prognosis during the last twenty years.

OBJECTIVE: This study was designed to establish prognostic factors for survival of patients with locally advanced or metastatic urothelial cancer. We have furthermore investigated changes in patient characteristics and treatment strategies during the last 20 years. PATIENTS AND METHODS: Between 1992 and 1997, a total of 156 patients with newly diagnosed recurrent locally advanced disease (nonresectable, radioresistant) and/or metastatic transitional cell carcinoma of the urothelial tract were included in a protocol evaluating clinical and laboratory prognostic factors at baseline. The relationship between these characteristics and survival was analyzed using univariate and multivariate methods. The results were compared to the survival results of similar patients treated previously from 1976 to 1991. RESULTS: Median survival after diagnosis of recurrent locally advanced or metastatic disease was 5.8 months. Multivariate analysis showed that good performance status (PS), normal alkaline phosphatase (AP), absence of liver metastases and chemotherapy were independent prognostic factors for long survival. An increase in survival was found when comparison was made with 240 patients treated in the period from 1976 to 1991, but the period of treatment had no independent importance in multivariate analysis. CONCLUSION: PS, AP and liver metastases are the major important prognostic factors in metastatic urothelial cancer. Stage migration and increased use of chemotherapy may have contributed to improved median survival during the last 20 years.

Pattern of metastases in relation to characteristics of primary tumor and treatment in patients with disseminated urothelial carcinoma.

PURPOSE: The anatomical pattern of recurrence and metastases in patients with urothelial cancer are described, and the relationship between treatment and features of the primary invasive tumor and the subsequent pattern of metastases is analyzed. MATERIALS AND METHODS: Between 1976 and 1991, 240 patients with recurrent or metastatic urothelial cancer were admitted to our department. RESULTS: The majority of the patients had recurrence within 2 years after initial diagnosis. Local recurrences and lung metastases were diagnosed significantly earlier than other metastases. Multiple sites were involved in more than half of the patients. The most common sites of recurrence were local in the bladder in 65% of the cases and bone in 35%, followed by lymph nodes in 26% and lung in 20%. The pattern of metastases was similar in patients with different histological findings, grade and location of the primary tumor. Patients younger than 60 years and those with cancer of the renal pelvis more often had distant metastases compared to older patients with bladder cancer. Local recurrences were less frequent in patients who had undergone cystectomy compared to those treated with radiotherapy only. Moreover, patients with local recurrences were likely to have metastases elsewhere. CONCLUSIONS: Bone was the most frequent site of metastases outside the pelvis and all patients suspected to have recurrence should be examined for bone metastases. The results indicate that the pattern of recurrence and metastases are not dependent on the features of the primary tumor.

Prognostic factors and significance of chemotherapy in patients with recurrent or metastatic transitional cell cancer of the urinary tract.

BACKGROUND: Prognostic factors for patients with disseminated transitional cell carcinoma of the urothelium (TCC) has been examined only in patients selected for studies with chemotherapy. This study was performed to determine important prognostic factors in patients with disseminated TCC and evaluate the impact of chemotherapy. METHODS: The prognostic factors for survival were analyzed in 240 patients with disseminated TCC admitted from 1976 to 1992. Information on prior medical history, baseline variables, and treatment were related to survival after dissemination. Both univariate and multivariate analyses were performed to identify factors of independent importance. RESULTS: Univariate analyses indicated that performance status; hemoglobin; leukocyte count; platelet count; concentrations of serum creatinine, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase; hydronephrosis; bone metastases; disease extension; and chemotherapy were related significantly to survival. Multivariate analysis demonstrated that a good performance status, a normal alkaline phosphatase concentration, and a normal serum creatinine concentration were independent prognosticators for long survival. When chemotherapy was included in the analysis, it was found to be the most important independent prognostic factor in conjunction with alkaline phosphatase and performance status. CONCLUSION: This study has established the importance of performance status and alkaline phosphatase as the most important prognostic factors of survival in patients with disseminated TCC regardless of treatment. Chemotherapy was found to be an independent prognostic variable that indicates a possible prolongation of survival in patients receiving chemotherapy.