Pancreas cancer as a second primary malignancy. A population-based study

BACKGROUND: The study of second primary malignancies may give clues to the etiology of various cancers. Little is known about risk factors for pancreatic carcinoma; therefore, its occurrence as a second primary malignancy was investigated. METHODS: Data from the Surveillance, Epidemiology, and End-Results (SEER) program were used for the period from January 1, 1973 through December 31, 1990. Person-years of follow-up for various cancer sites were calculated, excluding the initial 6 months after diagnosis, and were multiplied times the age- and sex-specific incidence rates for pancreas cancer to calculate the expected number of second primary pancreas cancer cases. The observed number of cases was divided by the expected number to estimate the relative risk (RR) of pancreas cancer as a second primary cancer, and 95% confidence limits were calculated. RESULTS: The risk of second primary cancer was elevated after lung cancer for men (RR 1.3, 95% CI 1.0-1.6) and women (RR 2.5, 95% CI 1.9-3.2). An elevation in risk also was found after head and neck cancer in women (RR 1.8, 95% CI 1.2-2.5) and bladder cancer in women (RR 1.5, 95% CI 1.1-2.0), but not in men. Other significant elevations were found after prostate cancer (RR 1.2, 95% CI 1.1-1.3), and a decreased risk was found after lymphoma in men (RR 0.2, 95% CI 0.0-0.8). CONCLUSIONS: Second primary pancreas cancer is increased after tobacco-related malignancies, particularly in females, supporting the role of cigarette smoking as a risk factor for pancreas cancer and suggesting a stronger effect of cigarette smoking for women. The elevation in risk after prostate cancer and the decreased risk after lymphoma in males need to be confirmed in other data sets.     

Observations on template switching during DNA replication through long inverted repeats

High dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly used in the treatment of patients with lymphoma. As previously shown with conventional treatments, second neoplasms are emerging as a long term complication of the procedure. In this study, we investigate the incidence of second neoplasm in a cohort of 171 patients treated with BEAM or BEAC regimens for Hodgkin's disease (n = 62) and non-Hodgkin's lymphomas (n = 109) followed up for a median of 52 months post ASCT. Six patients developed six second malignancies 12 to 105 months after ASCT: fibrolamellar carcinoma of the liver, malignant fibrous histiocytoma, pancreatic carcinoma, squamous cell carcinoma of the lung, invasive carcinoma of the vulva and acute myelogenous leukemia. The cumulative actuarial risk for developing second malignancy is 16.7% (95% confidence interval: 5.9-39.3%) 13 years after transplant. The age-adjusted incidence of cancer in the study group is 4.1 times higher than that of primary cancer in the general population. These data confirm that ASCT recipients are at increased risk of later malignancies. This complication adds significant morbidity and mortality to the transplant process and therefore, needs to be taken into account in long term evaluation of new strategies which involve early intensification in the treatment of lymphomas.     

Synchronous and metachronous primary malignancies in organs other than the stomach in patients with early gastric cancer

BACKGROUND/AIMS: We investigated the outcomes of patients with early gastric cancer, with special reference to the prognosis of patients with synchronous or metachronous primary malignancies in organs other than the stomach. PATIENTS AND METHODS: Among 890 patients with early gastric cancer, 97 (10.9%) had synchronous or metachronous primary malignancies in organs other than the stomach. Ten-year survival rates were compared between patients who had additional malignancies and patients who had early gastric cancer but no other malignant disease (control group). RESULTS: Synchronous primary malignancies were detected in 32 patients and metachronous primary malignancies were detected in 65 patients (17 had developed before gastrectomy and 48 developed after gastrectomy). Hepatic cell carcinoma, lung cancer and colorectal cancer were frequently detected between 2 and 24 years after gastrectomy. The 10-year survival rate was 80.8% for 769 patients in the control group but it was only 49.7% for the 92 patients with additional malignancies. Moreover, metachronous malignant disease was found more over 10 years after gastrectomy in 30 of the 48 cases (62.5%). CONCLUSIONS: These results suggest the importance of long-term follow-up for detection of metachronous carcinomas at sites other than the stomach for patients with early gastric cancer.     

Renal masses simulating primary renal cell carcinoma in patients with advanced malignancies

Most patients who present with a large solid renal mass and evidence of advanced malignancy will have primary renal cell carcinoma but a small subset with similar features have different and more treatable malignancies. We identified 7 patients with clinical and radiological findings suggestive of metastatic renal cell carcinoma who were ultimately diagnosed as have non-Hodgkin's lymphoma (5), germ cell tumor (1) or transitional cell carcinoma (1). Two of these patients presented with abdominal pain, gross hematuria and a flank mass. Computerized tomography was interpreted as showing renal cell carcinoma in all patients, although lymphoma and sarcoma were included in the differential diagnoses in 2. With the correct diagnosis and appropriate therapy, 4 of the 7 patients are currently disease-free. We emphasize the need for histological documentation in such patients in view of curative therapy available for possible underlying neoplasms simulating renal cell carcinoma.     

Coincident renal cell carcinoma and nonHodgkin's lymphoma: the M. D. Anderson experience and review of the literature

PURPOSE: We recently observed nonHodgkin's lymphoma and renal cell carcinoma occurring simultaneously in several patients. We determine whether the incidence of co-occurrence of the 2 malignancies is greater than expected based on the incidence of each disease in the general population. MATERIALS AND METHODS: Patients diagnosed with simultaneous renal cell carcinoma and nonHodgkin's lymphoma were identified through the medical informatics data base at our cancer center. Charts of all patients were reviewed to collect detailed demographic information and confirm both diagnoses. United States population based cancer statistics (Surveillance, Epidemiology and End Results Program data) were used to arrive at the expected age adjusted incidence of co-occurrence of these diagnoses, and statistical analysis was performed to ascertain any differences between expected and observed incidences. RESULTS: We identified 41 cases with both diagnoses between 1954 and 1995, including 21 diagnosed after 1987. The latter group was used for statistical analysis. The observed rates of renal cell carcinoma developing in the nonHodgkin's lymphoma population (1.86) and nonHodgkin's lymphoma developing in the renal cell carcinoma population (2.67) were greater than expected and both reached statistical significance. CONCLUSIONS: There is a higher than expected incidence of co-occurrence of renal cell carcinoma and nonHodgkin's lymphoma. The cause remains speculative.     

Increased cutaneous toxicity to ionizing radiation in HIV-positive patients. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR)

Little is known about the etiology of esophageal and gastric cardia adenocarcinoma (EGA), a cancer with one of the fastest-rising incidences in the developed world. To explore the etiology of this cancer, we conducted a retrospective cohort analysis using data from the Surveillance, Epidemiology and End Results Program of the United States National Cancer Institute to study EGA and esophageal squamous cell carcinoma (ESC), in association with cancers of other sites. Standardized incidence ratios, adjusted for age, sex, and time period, were calculated as a measure of the relative risk (RR) of developing a second primary cancer (EGA or ESC) following a given first primary site. We found a moderately elevated risk of EGA following cancers of the lung (RR = 1.9 in men and RR = 2.0 in women) and of the head and neck (RR = 2.1 in men and RR = 6.3 in women) and a strongly elevated risk of ESC following cancers of the lung (RR = 2.8 in men and RR = 5.1 in women) and of the head and neck (RR = 9.6 in men and RR = 38.8 in women). A significantly elevated risk following breast cancer in women was observed for both EGA (RR = 2.6; 95% confidence interval, 1.8-3.7) and ESC (RR = 1.4; 95% confidence interval, 1.1-1.9). We also found a significantly elevated risk of EGA following bladder (RR = 2.0), colorectal (RR = 1.7), and prostate (RR = 1.4) cancer in men and of ESC following colorectal cancer (RR = 1.7) in women in this study. The strong association with tobacco-related malignancies in this study reinforces the role of tobacco in the etiology of esophageal cancers, which appears stronger for squamous cell carcinoma than for adenocarcinoma and stronger in women than in men. The study also suggests a possible shared etiology between esophageal adenocarcinoma and colorectal cancer in men and provides new evidence about the association of both adenocarcinoma and squamous cell carcinoma of the esophagus with breast cancer in women. Findings of this study provide clues to the etiology of EGA and ESC.     

Rheumatoid arthritis and the risk of malignancy

OBJECTIVE: To determine the relative risks of malignancy and of site-specific malignancies in patients with rheumatoid arthritis (RA). METHODS: In a prospective cohort study, 862 patients with RA (96% white) were enrolled from 1966 to 1974 and were followed up for up to 35 years (mean 17.4 years) at the University of Saskatchewan Rheumatic Disease Unit. All diagnoses of cancer were cross-referenced with the Provincial Cancer Registry. Expected cancer incidence rates were determined based on province of Saskatchewan population statistics matched to each study patient for age, sex, and calendar year. Standardized incidence ratios (SIRs) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. RESULTS: A total of 136 cases of cancer were observed compared with 168 expected (SIR 0.80, P = 0.011 [95% CI 0.67-0.95]). The relative risk of colorectal malignancy was significantly reduced in the RA study population (SIR 0.52, P = 0.037 [95% CI 0.25-0.96]). A significant excess of leukemia was found (SIR 2.47, P = 0.026 [95% CI 1.12-4.69]), whereas the incidence rates for Hodgkin's disease and non-Hodgkin's lymphoma and all other site-specific malignancies were not found to be significantly different from general population rates. CONCLUSION: In our cohort of RA patients, colorectal cancer was detected in only half the expected number of patients. This risk reduction may be related to long-term nonsteroidal antiinflammatory drug (NSAID) use in RA, as has been suggested in several other studies of long-term NSAID use. An increased risk of leukemia was confirmed. This may be due to the persistent immune stimulation associated with RA itself, since other potential explanatory factors for increased leukemia were not apparent. Despite the excess of hemopoietic malignancy and despite treatment of RA with potentially oncogenic agents, the overall risk of malignancy was reduced in this RA cohort.     

Sudden death in young people with mitral valve prolapse or mitral valve prolapse in young people who died suddenly

We report multiple malignancies in four patients with metachronous renal adenocarcinomas. The group of patients includes two women treated for primary breast and ovarian cancer and two men with prostate and colon cancer respectively. The occurrence of renal cancer following these primary solid tumors was not associated with previous treatments. The authors review the literature and discuss pathogenic mechanisms underlying renal cell carcinoma.     

Stroke volume response to cycle ergometry in trained and untrained older men

We evaluated the risk of development of second primary cancers, with particular reference to subsequent hepatocellular carcinoma (HCC), in 592 patients diagnosed as non-Hodgkin's lymphoma (NHL), at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978-1994, 2,163 person-years of observation were accrued, and 27 of the patients developed a second primary cancer, yielding an observed-to-expected ratio (O/E) of 1.53 [95% confidence interval (CI) = 1.01-2.23]. Significant excess risk was noted for primary liver cancer (PLC; O/E = 4.36, 95% CI = 1.99-8.28; O = 9) and non-lymphocytic leukemia (O/E = 26.17, 95% CI = 5.26-76.46; O = 3). The excess risk of PLC was relatively constant within the first 10 years after the NHL diagnosis. Patients who received chemotherapy as the NHL treatment had a significantly increased risk of PLC (O/E = 5.91, 95% CI = 2.70-11.23; O = 9). Their clinical reports indicated that all nine patients with PLC were diagnosed as HCC, and eight of them had clinical and/or histologic evidence of cirrhosis at the time of HCC diagnosis. None of the nine patients had a history of blood transfusion between the first NHL treatment and the diagnosis of HCC. These findings suggested that Japanese NHL patients might have an increased risk of developing HCC, and they indicated the importance of medical surveillance for liver malignancies, as well as subsequent leukemias. Possible explanations for the excess risk of subsequent HCC are discussed.     

Risk of cancer among patients with cutaneous basal cell carcinoma

A population-based cohort of 37,674 patients diagnosed during the period 1978-1991 and registered in the Danish Cancer Registry with basal cell carcinoma of the skin (BCC) were followed for the occurrence of new malignancies. BCC patients experienced significantly increased cancer incidence rates compared with the general Danish population. The elevated cancer risk was not restricted to new cutaneous malignancies. Cancers at various sites, including lip, salivary glands, larynx, lung, breast, kidney and non-Hodgkin lymphoma occurred in significant excess. Patients diagnosed with BCC before the age of 60 years were at higher risk of developing new malignancies than patients diagnosed with BCC at an older age. This age association pertained particularly to breast cancer, testicular cancer and non-Hodgkin lymphoma.     

FPSUND: a pan-Canadian evaluation of a clinical classification of urinary incontinence

To obtain quantitative information on the risk of invasive cancers following a diagnosis of basal cell carcinoma (BCC) of the skin, patients with incident BCC cases listed in the cancer registries of the Swiss cantons of Vaud and Neuchatel between 1974 and 1994 were actively followed up through December 31, 1994, for the occurrence of subsequent invasive neoplasms. Among 11,878 persons with incident BCC who were followed for a total of 76,510 person-years at risk, 1,543 metachronous cancers were observed versus 1,397.9 expected, corresponding to a standardized incidence ratio (SIR) of 1.1 (95% confidence interval (CI) 1.0-1.2). However, after exclusion of skin cancers (mostly squamous cell carcinoma and melanoma), 975 second primary cancers were observed versus 1,059 expected (SIR = 0.9, 95% CI 0.8-1.0). Significant excesses were registered for cancer of the lip (SIR = 2.2), for squamous cell skin cancer (SIR = 4.5) and melanoma of the skin (SIR = 2.5), and for non-Hodgkin's lymphoma (SIR = 1.9). The SIRs were also above unity, though not significantly, for cancers of the salivary glands (SIR = 2.8) and the small intestine (SIR = 2.1) and for soft-tissue sarcomas (SIR = 1.7). The SIR for lung cancer was 0.9. The SIRs for salivary gland and skin cancer were appreciably greater below age 70 years. For most sites, particularly for squamous cell cancer and melanoma of the skin, the SIRs remained elevated 5 or more years after BCC diagnosis. The cumulative incidence of squamous cell skin cancer was 13% at 19 years; this stresses the importance of carefully monitoring skin lesions among persons previously diagnosed with BCC.     

Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract

A retrospective analysis of 74 cases of transitional cell carcinoma of the renal pelvis and ureter treated at this institution over the past 30 years is presented. When nephrectomy alone or incomplete nephroureterectomy was performed, subsequent transitional cell carcinoma developed in 30% of the ureteral stumps. Subsequent bladder carcinoma occurred in 25% of the patients with primary upper urinary tract carcinoma. The type of initial surgery performed did not appear to influence this incidence of subsequent bladder tumors. Contralateral upper urinary tract carcinoma developed in only one patient. When nephroureterectomy is performed for carcinoma of the renal pelvis and ureter, a cuff of bladder that includes the ureteral orifice should be removed to obviate recurrent disease in the ureteral stump. Since single-incision nephroureterectomy did not include the intramural ureter in 50% of the cases in which it was performed, a second incision may be required for adequate exposure.     

Clinical manifestations and therapies of AIDS associated tumors

We are giving an overview over the clinical features and different therapeutic options of HIV associated malignancies. There are three AIDS-defining malignancies: - Kaposi's sarcoma - Non-Hodgkin's lymphoma (NHL) - cervical cancer. In Kaposi sarcoma there is a broad therapeutic spectrum from cryotherapy to systemic chemotherapy depending on the site and stage of the Kaposi sarcoma. In NHL early therapeutic intervention is necessary because of the fast progress of the tumor. The cervical cancer in HIV-infected women seems to be more aggressive than in non-infected and also needs early therapeutic intervention. Many other tumors seem to occur more frequently in patients with HIV infection: anorectal cancer, malignant testicular tumors, lung cancer, Hodgkin's lymphoma, basal cell carcinoma, squamous cell carcinoma, and even malignant melanoma. The cancer incidence in HIV-patients seems to be higher among nonblacks. Most of the immunodeficiency associated tumors are virus induced and they are accompanied by a persistent viral infection, including HHV-8 in Kaposi's sarcoma; Epstein Barr virus (EBV) in NHL; and human papillomavirus (HPV) in cervical cancer. But there are also types of virus induced tumors which are not frequently associated with HIV-infection like the primary hepatocellular carcinoma in patients with hepatitis B virus infection.     

Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers

A new tumor suppressor gene PTEN/MMAC1 was recently isolated at chromosome 10q23 and found to be inactivated by point mutation or homozygous deletion in glioma, prostate and breast cancer. PTEN/MMAC1 was also identified as the gene predisposing to Cowden disease, an autosomal dominant cancer predisposition syndrome associated with an increased risk of breast, skin and thyroid tumors and occasional cases of other cancers including bladder and renal cell carcinoma. We screened 345 urinary tract cancers by microsatellite analysis and found chromosome 10q to be deleted in 65 of 285 (23%) bladder and 15 of 60 (25%) renal cell cancers. We then screened the entire PTEN/MMAC1 coding region for mutation in 25 bladder and 15 renal cell primary tumors with deletion of chromosome 10q. Two somatic point mutations, a frameshift and a splicing variant, were found in the panel of bladder tumors while no mutation was observed in the renal cell carcinomas. To screen for homozygous deletion, we isolated two polymorphic microsatellite repeats from genomic BAC clones containing the PTEN/MMAC1 gene. Using these new informative markers, we identified apparent retention at the gene locus indicative of homozygous deletion of PTEN/MMAC1 in four of 65 bladder and 0 of 15 renal cell tumors with LOH through chromosome 10q. Identification of the second inactivation event in six bladder tumors with LOH of 10q implies that the PTEN/MMAC1 gene is occasionally involved in bladder tumorigenesis. However, the low frequency of biallelic inactivation suggests that either PTEN/MMAC1 is inactivated by other mechanisms or it is not the only target of chromosome 10q deletion in primary bladder and renal cell cancer.     

Transitional carcinomas of the urinary tract: synchronous and metachronous lesions

OBJECTIVE: The urothelium is a pseudostratified cylindrical epithelium that lines the calices, renal pelvis, urethers, bladder, part of the urethra and part of the prostate ducts. Transitional cell carcinoma (TCC) is a malignant neoplasia that can appear in any site where urothelium is present, being the bladder the most frequently affected organ. We performed an analysis of our experience and conducted a literature-based metanalysis to evaluate the coexistence of tumoral lesions at different locations in the urinary tract. MATERIAL AND METHODS: Between 1983 and 1993, 397 patients with TCC lesions involving the upper urinary tract (UUT), bladder, urethra or prostate, were diagnosed and treated. Coexistence, either synchronic or metachronic, of several lesions in different sites of the urinary tract was considered as a multiple tumor. RESULTS: Overall, 440 tumors were diagnosed in 397 patients. A single lesion appeared in 360 patients, while 37 presented multiple locations with a total of 79 tumors. The lesions were located at the following levels: 17 renal, 21 uretheral, 372 vesical, 13 in the urethra and 17 in the prostate ducts. According to the location, the frequency of single lesions was: UUT 58%, bladder 91%, urethra 8% and prostate ducts 35%. Synchronic UUT and intravesical tract tumors develops in 1% and 4% of patients with bladder TCC, respectively. Two percent of vesical tumors showed metachronic relationship with UUT tumors and the same rate was seen for intravesical lesions. CONCLUSIONS: Urothelial UUT tumors have a typical nosologic entity with specific features. Their coexistence with vesical tumors is frequent. When tumors of the bladder occur after a UUT tumor the interval of highest incidence between diagnoses is 2-3 years, and there are no histological risk factors among them for prognosis. Transitional cell prostatic urethral tumors are most often secondary to histologically similar, poor prognosis, bladder tumors, and usually synchronic.     

AIDS and neoplasms in Mexico

OBJECTIVE: To describe the epidemiological profile of AIDS and malignancies in Mexico. MATERIAL AND METHODS: The study population included a group of AIDS patients seen at four National Institutes of Health and one at a general hospital in Mexico City, from 1983 to 1992. Demographic, clinical and laboratory information was obtained. RESULTS: A total of 202 patients were studied; 199 men and three women. The mean age was of 34.5 years (range 18-67 years). Kaposi's sarcoma was the most frequent malignancy, with 166 cases, followed by non-Hodgkin's lymphoma, with 33 cases. The three women had non-Hodgkin's lymphoma, one of them associated with cervical carcinoma. Rectal cancer was present in three cases. DISCUSSION: The spectrum of AIDS-associated malignancies in Mexico is similar to that described in other populations. The early diagnosis of this complication is necessary, as well as the search for therapeutic actions to prevent severe immunosuppression and the consequent appearance of malignancies.     

A conceptual model of adaptation to illness and quality of life for cancer patients treated with bone marrow transplants

OBJECTIVES: Our goal was to determine the risk of cancer after hospitalization for endometriosis. STUDY DESIGN: Records of 20,686 women hospitalized with endometriosis during the period 1969 to 1983, as identified through the nationwide Swedish Inpatient Register, were linked against the National Swedish Cancer Registry through 1989 to identify all subsequent diagnoses of cancer. The study subjects were followed up for a mean of 11.4 years, with the cohort contributing 216,851 woman years of follow-up. Standardized incidence ratios were computed by the use of age- and period-specific incidence rates derived from the Swedish population. Because of the high proportion of subjects with gynecologic operations (55.6%), evaluation of the risk of gynecologic cancers involved truncation of person years at the time of any such operation. RESULTS: The overall cancer risk was 1.2 (95% confidence interval 1.1 to 1.3). Significant excesses were observed for breast cancer (standardized incidence ratio = 1.3, 95% confidence interval 1.1 to 1.4), ovarian cancer (1.9, 1.3 to 2.8), and hematopoietic malignancies (1.4, 1.0 to 1.8); this latter excess was largely driven by an excess risk of non-Hodgkin's lymphoma (1.8, 1.2 to 2.6). The risk of ovarian cancer was particularly elevated among subjects with a long-standing history of ovarian endometriosis (4.2, 2.0 to 7.7). Cervical cancer risk was slightly reduced (0.7, 0.4 to 1.3) whereas no association was observed for cancer of the endometrium (1.1, 0.6 to 1.9). CONCLUSIONS: These findings suggest that further attention be given to the risk of breast, ovarian and hematopoietic cancers among women with endometriosis and to exploring possible hormonal and immunologic reasons for the excess risks.     

Molecular diagnosis of mutations responsible for recurrent and severe forms of primary congenital glaucoma

BACKGROUND: A markedly increased incidence of malignancy in transplant recipients is well recognized. However, the incidence and pattern of post-transplantation malignancies shows some discrepancy among different reports. The renal transplant recipients monitored at Taichung Veterans' General Hospital comprise the largest group in Taiwan. An analysis of the characteristics of post-transplant malignancies emphasizes the differences from malignancies that occur in the Taiwanese general population and those reported in Western countries. METHODS: The incidence and characteristics of de novo malignancy in 390 renal transplant recipients who underwent renal transplantation between May 1983 and June 1996 were analyzed. A total of 232 men and 158 women (mean age at transplantation: 38.5 +/- 10.7 years) were included. The relative risk for developing malignancies was calculated based on the sex- and age-matched cancer incidence of reference for the Taiwanese population; data from the Cancer Registry Annual Report in Taiwan (1989) was obtained for comparison. RESULTS: A total of 25 cancers were diagnosed in 24 renal transplant recipients, for an incidence of 6.2%. The relative risk of renal malignancy was 13.8-fold higher among transplant recipients than in the general population. The impact of gender and age on the development of post-transplantation malignancy was not significant. The most common types of cancer were transitional cell carcinoma (TCC) of the urinary tract (8/25), and hepatoma (8/25), followed by two cases of Kaposi's sarcoma. Aside from immunosuppressive agents, the high incidence of hepatoma and TCC may be attributed to the high incidence of hepatitis infection and the possible carcinogenic effect of abnormal milieu induced by uremia per se. Survival was largely dependent on the extent of disease at presentation, and post-transplantation cancer did not show more aggressive behavior if detected early. CONCLUSIONS: The high cumulative incidence of malignancies makes it imperative to define an effective safe immunosuppressive regimen to achieve a lower risk of malignancies. In the future, the prime approach to treatment of post-transplantation malignancies should begin with early detection and ensuing aggressive treatment to improve the outcome.     

Does prostate transitional cell carcinoma preclude orthotopic bladder reconstruction after radical cystoprostatectomy for bladder cancer?

PURPOSE: We determined if urethral preservation and orthotopic bladder replacement in patients with transitional cell carcinoma within the prostatic urethra or prostate placed these patients at risk for urethral recurrence or death. MATERIALS AND METHODS: The clinical course of all patients undergoing urethral preservation and orthotopic bladder replacement was reviewed. The urethra was sacrificed only if the distal prostatic urethral margin was positive for transitional cell carcinoma. The pathological T stage and the grade of the primary malignancy, local recurrence, site of recurrence (urethral, pelvic, distant) and death were documented. RESULTS: Of 81 patients 70 were evaluable (June 1996) with a mean followup of 35 months. Of the 70 patients 48 were alive without evidence of disease for a mean of 38 months (range 8 to 107) and 5 died without evidence of disease. Eight of these 53 patients (15%) had prostatic involvement (carcinoma in situ in 6, intraductal carcinoma in 1 and stromal invasive transitional cell carcinoma in 1). Of the 70 patients 17 had disease recurrence (13 died of disease and 4 are alive, 1 of whom had urethral recurrence without initial prostatic transitional cell carcinoma). Of the 17 patients (35%) 6 had transitional cell carcinoma prostatic involvement (carcinoma in situ in 4 and stromal invasion in 2), and 5 of these 6 died, none with or of urethral recurrence but of the primary bladder pathology. Of these 5 patients 1 had stromal invasive transitional cell carcinoma of the prostate and experienced a bulbar urethra recurrence at 1 month and a pelvic recurrence at 3 months, and died at 5 months. Death was not secondary to the urethral recurrence. Thus, of the 14 patients who had prostatic transitional cell carcinoma, only 1 had urethral recurrence (7%), and this recurrence did not present as the cause of death. CONCLUSIONS: The guidelines for urethral resection can be relaxed, increasing the opportunities for orthotopic reconstruction, without placing the patients at increased risk for death of transitional cell carcinoma.