Arnon Krongrad

Marriage and mortality in prostate cancer

PURPOSE We evaluated the association of marital status and survival in patients with prostate cancer. MATERIALS AND METHODS Using the 146,979 prostate cancer patients of the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of mortality. RESULTS Married patients had significantly longer median survival than those who were divorced, single, separated or widowed. In models that controlled for age, stage, race and treatment, married patients had a significantly lower risk of mortality than those who were divorced, single, separated or widowed. CONCLUSIONS Several hypothetical models can explain the association of marital status and mortality in men with prostate cancer. The most attractive model relies on the putative salutary effects of being married on social support and/or mood. A social support and depressed mood model of mortality raises the possibility that in prostate cancer quality of life determines quantity of life. Understanding the relationships among marital status, social support, mood and mortality could open the way to rational strategies for postponing death in men with prostate cancer.

Assessment of endpoints for clinical trials for localized prostate cancer

OBJECTIVES The AUA Practice Guidelines Panel convened to address the issue of appropriate endpoints for assessment of treatment modalities for localized carcinoma of the prostate. METHODS A review of the literature and the design of existing clinical trials produced a consensus, which was presented to and critiqued by the members of the general conference. RESULTS The pitfalls associated with identification of local failure endpoints were discussed, and the more accurate endpoints of freedom from metastatic progression and overall survival were recognized. The strict definition that must be fulfilled for intermediate endpoints to become surrogates for metastasis free and/or survival endpoints was stressed. For more efficient and rapid conduct of future clinical trials, the urgent need to validate such surrogate endpoints by evaluation in randomized control trials is obvious. PSA, while an indicator of disease activity and a critical marker for estimating disease progression or regression in response to therapy, is not a surrogate for metastasis free or overall survival. CONCLUSION Until surrogate endpoints are validated, the committee has evaluated the endpoints in current use, reviewed their limitations, and stressed the importance of quality-of-life assessment together with the traditional endpoint assessment.

Involvement of CD44 and its variant isoforms in membrane-cytoskeleton interaction, cell adhesion and tumor metastasis

SummaryCD44s (standard form of CD44) is a transmembrane glycoprotein whose external domain displays extracellular matrix adhesion properties by binding both hyaluronic acid (HA) and collagen. The cytoplasmic domain of CD44s interacts with the cytoskeleton by binding directly to ankyrin. It has been shown that post-translational modifications, such as phosphorylation (by protein kinase C), acylation (by acyl-transferase) and GTP-binding enhance CD44s interaction with cytoskeletal proteins. Most importantly, the interaction between CD44s and the cytoskeletal protein, ankyrin, is required for the modulation of CD44s cell surface expression and its adhesion function.Recently, a number of tumor cells and tissues have been shown to express CD44 variant (CD44v) isoforms. Using RT-PCR and DNA sequence analyses, we have found that unique CD44 splice variant isoforms are expressed in both prostate and breast cancer cell lines and carcinomas. Most importantly, intracellular ankyrin is preferentially accumulated underneath the patched/capped structures of CD44 variant isoform in both breast and prostate cancer cells attached to HA-coated plates. We propose that selective expression of CD44v isoforms unique for certain metastatic carcinomas and their interaction with the cytoskeleton may play a pivotal role in regulating tumor cell behavior during tumor development and metastasis.

Reliability of Spanish Translations of Select Urological Quality of Life Instruments

PURPOSE Many patients with urological disease do not speak English. In medical studies restricting patients to those who speak only English undermines efforts to understand disease because restrictions decrease efficiency of patient recruitment, and because language and culture are associated with variable outcomes. In Spanish speaking locations, such as South Florida, studies would suffer severe selection bias if patients were required to speak English. To allow grouping in future studies of English and Spanish speaking patients we examined the English-Spanish reliability of select instruments that measure health related quality of life in patients with urological disease. MATERIALS AND METHODS We assembled available Spanish versions and translated English versions of questions regarding satisfaction, the American Urological Association symptom index, the University of California, Los Angeles Prostate Cancer Index and a pain inventory. We then examined English-Spanish reliability by asking bilingual men 50 years old or older to complete English and Spanish versions at the same sitting. A convenience sample was recruited from outpatients and volunteers at the Miami Veterans Affairs Medical Center and population based subjects living in largely Hispanic Hialeah, Florida. Reliability estimates were calculated with kappa coefficients for categorical data and intraclass correlation coefficients for quantitative data. RESULTS A total of 100 subjects a median of 59 years old completed the questionnaire, including 55 born in Puerto Rico or Cuba, while the remainder were born at various sites throughout the Americas and Spain. Reliability estimates showed that kappa = > 0.81 for almost all items. For 2 items relating to health and social interactions reliability was poor, and stratification showed that poor reliability was primarily a feature of subjects in good health who are theoretically socially active. CONCLUSIONS Almost all items tested have excellent English-Spanish reliability in a mixed sample of bilingual men. Nonreliability of 2 items relating to health and social interactions probably originates from the effect of language on perception, and invalidates English and Spanish grouping of these items. Because the sample represents many dialects of Spanish, the translations tested may be transported to other cities. In studies that use these instruments investigators can reasonably group answers from English and Spanish speaking study subjects or study the effects of acculturation on quality of life.

Predictors of general quality of life in patients with benign prostate hyperplasia or prostate cancer

PURPOSE Studies in disease specific populations have emphasized disease specific quality of life with little study of general quality of life. Furthermore, studies of general quality of life in disease specific populations have mostly examined the importance of disease specific variables, and have generally yielded poor correlations of such variables and general quality of life. We attempted to model the emotional component of general quality of life in patients with prostate disease. MATERIALS AND METHODS We integrated prospectively collected disease specific and nonspecific clinical and self-reported patient data. We also applied neural network and more conventional statistical tools to examine the relative use of various available analytical methodologies in modeling general quality of life. RESULTS Neural networks created reasonably good models of the emotional component of general quality of life. Logistic regression analysis also created reasonably good models and, given current computational schemes, allowed for identification of significant inputs in the models more readily than did the feed-forward, back propagation neural networks. All models of general quality of life relied primarily on disease nonspecific inputs, including social support, activities of daily living and coping. CONCLUSIONS Our observations suggested that efforts to optimize general quality of life in patients with prostate disease must integrate disease nonspecific variables.

Radical prostatectomy: geographic and demographic variation

OBJECTIVES Previous reports have documented a geographic variation in the use of radical prostatectomy. We examined whether this phenomenon can be explained by factors other than geography alone. METHODS This study was based on the data from nine geographic regions of the Surveillance, Epidemiology, and End Results (SEER) program for the years 1983 through 1994. Patients with localized or regional prostate cancer were included in the analysis. Logistic regression analysis was used to investigate the influence of geographic and demographic factors on the use of radical prostatectomy. The squared multiple correlation coefficient R(2) was used to measure the proportion of variation in the selection of radical prostatectomy explained by each factor of interest. RESULTS As previously reported, the use of radical prostatectomy was significantly associated with geographic location; the degree of geographic variation varied as a function of age and was most dramatic in the youngest (younger than 45 years) and the oldest (75 years or older) groups. Overall, however, geography explained less than 2% of the total variation in the use of radical prostatectomy. Age was the most important factor that influenced the use of radical prostatectomy. CONCLUSIONS Geography explains only a small proportion of the variation in the use of radical prostatectomy. In fact, of the factors examined, only age appeared to meaningfully explain the variation in the use of radical prostatectomy. Overall, our ability to explain the variation in the use of radical prostatectomy remains meager, and new factors must be identified if we are to better understand how patients and physicians make clinical decisions.

Variation in prostate cancer survival explained by significant prognostic factors

PURPOSE Traditional survival analytical tools do not reveal the ability of significant prognostic factors to predict (that is, explain variation in) survival. We used survival data in patients with prostate cancer to illustrate how the association of factors with survival diverges from their ability to explain variation in survival; bladder cancer was included as a point of general comparison. MATERIALS AND METHODS We used the 1973 to 1990 records of the Surveillance Epidemiology and End Results program. Multivariate proportional hazards models were used to identify factors that significantly associated with survival. The proportion of variation explained by these factors was estimated with the Schemper method. RESULTS The dataset included 10,636 patients with prostate cancer and 1,070 with bladder cancer. Median survival was significantly longer in prostate than bladder cancer; other characteristics were similarly distributed. Age, stage and marital status were associated with survival in both cancers (p value range 0.0001 to 0.0009). The total proportion of variation explained was 7.1% and 32.1% for prostate and bladder cancer, respectively. In prostate cancer, age, stage and marital status explained 0.6, 5.5 and 0.4%, of the adjusted proportion of variation explained, respectively, and in bladder cancer, they explained 14.7, 8.9 and 0.6%, respectively. CONCLUSIONS Proportional hazards models identified but did not reveal the ability of significant prognostic factors to explain variations in survival. The proportion of variation explained analyses illustrate why predicting survival is so difficult, especially in prostate cancer. The prognostic factors used do not possess the ability to explain variation in survival; new prognostic factors must be identified.

Radiation therapy in non-surgically-treated nonmetastatic prostate cancer: geographic and demographic variation

OBJECTIVES To examine the geographic variation in the use of radiation to treat nonmetastatic prostate cancer and to identify factors that explain the variation in the United States. METHODS This study was based on data from the nine geographic regions of the Surveillance, Epidemiology, and End Results Program for 1983 through 1996. Patients with localized or regional prostate cancer who did not undergo surgical treatment were included in the analysis. Logistic regression analysis was used to investigate the influence of geographic and demographic factors on the use of radiation. The squared multiple correlation coefficient R(2) was used to measure the proportion of variation in the selection of radiation explained by each factor of interest. RESULTS Compared with San Francisco, the adjusted odds ratios for 6 of the 8 geographic areas had highly significant P values, suggesting the use of radiation therapy varies from region to region. However, geographic location only explained less than 3% of the total variation in the use of radiation. The geographic location explained a much higher proportion of variation in the youngest (younger than 55 years) and the oldest (80 years old or older) groups. Overall, age was the most important factor that influenced the use of radiation. CONCLUSIONS The finding that geographic location explains a significant proportion of the variation in the use of radiation in the youngest and oldest age groups demonstrates the outcome of longstanding controversies in the nonsurgical treatment of prostate cancer. Documenting the impact of the interaction of age and geographic location on the treatment approaches provides for better understanding of the impact of patients and physicians making clinical decisions in the management of nonmetastatic prostate cancer.

Overall and disease-specific survival after radical prostatectomy: geographic uniformity

OBJECTIVES To examine whether the survival (both overall and disease-specific) of patients who underwent radical prostatectomy varies from region to region in the United States. Previous reports have documented a geographic variation in the use of radical prostatectomy. METHODS This study was based on the data from nine geographic regions of the Surveillance, Epidemiology, and End Results Program (SEER) for 1983 through 1992. Patients with localized prostate cancer who underwent radical prostatectomy were included in the analysis. A proportional hazards model was used to investigate whether geographic variation is associated with both overall and disease-specific survival. RESULTS From 1983 through 1992, the SEER Program collected information from nine geographic regions on 66,293 patients with localized prostate cancer (mean age 71.8 +/- 8.4 years), who had SEER grade codes of 1, 2, or 3. Of these patients, 11,429 (mean age 65.3 +/- 6.5 years) underwent radical prostatectomy and lymph node dissection. Coxs proportional hazards analyses revealed that the impact of geographic location on both overall and disease-specific survival in patients who underwent radical prostatectomy was not statistically significant. CONCLUSIONS The results of this study indicate that the survival (both overall and disease-specific) of patients with localized prostate cancer who underwent radical prostatectomy is not influenced by geographic location, suggesting that their survival is relatively uniform across the geographic regions in the United States.

Bilateral Ureteral Obstruction After Asymptomatic Appendicitis

X 41-year-old man presented elsewhere in January 1995 with gross hematuria but no pain, dysuria, decreasing urine output, stones or fever. Excretory uography and cystoscopy revealed no source of bleeding and the hematuria resolved spontaneously. The patient continued to have intermittent, painless, gross hematuria every few months and presented to us in August 1996. Excretory urography revealed bilateral hydroureteronephrosis. Computerized tomography demonstrated thickening of the pelvic and retroperitoneal organs consistent with an inflammatory process. Retrograde pyelography revealed bilateral distal ureteral narrowing and a filling defect in the left mid ureter (see figure). LeR ureteroscopy and biopsy showed inflammation. Urine cytology revealed reactive urothelial cells and atypia. A barium enema showed diverticulosis and narrowing at the mid sigmoid colon. Colonoscopy demonstrated an extrinsic compression at thc level of the mid sigmoid colon. Abdominal exploration revealed a necrotic perforated appendix and abscess, and widespread pelvic inflammatory changes compressing both ureters. Left ureterotomy demonstrated a 4 mm. stone. The mass surrounding the left ureter was excised and the ureter was repaired by urcteroureterostomy . On the right side distal ureterectoniy and reimplantation with a psoas hitch were performed to bypass the obstructing phlegmon. Convalescence was uneventful. Accepted for publication November 8, 1996. Retrograde pyelo ama demonstrate right ureteral narrowing (A) and left ureteral &g defect (B) .