Biomedical subjects

M W Kattan

Publications and source records attributed to M W Kattan.

At least 19 recordsLinked to original sources

PubMed2007

Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram.

PURPOSE: Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history. Statistical models have been proposed to predict indolent cancer. We validated and updated model predictions for a screening setting. MATERIALS AND METHODS: We selected 247 patients with clinical stage T1C or T2A from the European Randomized Study on Screening for Prostate Cancer who were treated with radical prostatectomy. We validated a nomogram that had previously been developed in a clinical setting. Predictive characteristics were serum prostate specific antigen, ultrasound prostate volume, clinical stage, prostate biopsy Gleason grade, and total length of cancer and noncancer tissue in biopsy cores. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements. Logistic regression was used to update the previous model and examine the contribution of other potential predictors. RESULTS: Overall 121 of 247 patients (49%) had indolent cancer, while the average predicted probability was around 20% (p <0.001). Effects of individual variables were similar to those found before and discriminative ability was adequate (AUC 0.76). An updated model was constructed, which merely recalibrated the nomogram and did not apply additional predictors. CONCLUSIONS: Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram. However, an updated model can support patients and clinicians when the various treatment options for prostate cancer are considered.

Aged↗

PubMed2006

Long-term outcome among men with conservatively treated localised prostate cancer.

Optimal management of clinically localised prostate cancer presents unique challenges, because of its highly variable and often indolent natural history. There is an urgent need to predict more accurately its natural history, in order to avoid unnecessary treatment. Medical records of men diagnosed with clinically localised prostate cancer, in the UK, between 1990 and 1996 were reviewed to identify those who were conservatively treated, under age 76 years at the time of pathological diagnosis and had a baseline prostate-specific antigen (PSA) measurement. Diagnostic biopsy specimens were centrally reviewed to assign primary and secondary Gleason grades. The primary end point was death from prostate cancer and multivariate models were constructed to determine its best predictors. A total of 2333 eligible patients were identified. The most important prognostic factors were Gleason score and baseline PSA level. These factors were largely independent and together, contributed substantially more predictive power than either one alone. Clinical stage and extent of disease determined, either from needle biopsy or transurethral resection of the prostate (TURP) chips, provided some additional prognostic information. In conclusion, a model using Gleason score and PSA level identified three subgroups comprising 17, 50, and 33% of the cohort with a 10-year prostate cancer specific mortality of <10, 10-30, and >30%, respectively. This classification is a substantial improvement on previous ones using only Gleason score, but better markers are needed to predict survival more accurately in the intermediate group of patients.

Aged↗

PubMed2006

Defining high risk prostate cancer with risk groups and nomograms: implications for designing clinical trials.

PURPOSE: Death from prostate cancer is usually preceded by metastases and it usually occurs in men with high risk disease who experienced biochemical failure with a short prostate specific antigen doubling time. We developed a model for determining disease specific survival in prostate cancer. MATERIALS AND METHODS: We used the model for defining high risk prostate cancer that was developed by the Radiation Therapy Oncology Group and combined it with the Kattan nomogram for predicting the risk of metastases. We selected 414 Radiation Therapy Oncology Group intermediate and high risk patients who were treated with external beam radiotherapy alone. Excluded were patients with low risk disease. The Kaplan-Meier product limit method was used to estimate the probability of freedom from biochemical failure, overall survival and disease specific survival. RESULTS: A significant difference was observed in freedom from biochemical failure, disease specific survival and overall survival among the 3 tertiles created by the nomogram using the cutoff points less than 8.5%, 8.5% to 15% and greater than 15% (p <0.001, 0.0002 and 0.0003, respectively). Only the risk of metastases using the categorized nomogram score (less than 8.5% and 8.5% to 15% vs greater than 15%), not preradiotherapy prostate specific antigen or Radiation Therapy Oncology Group risk (Radiation Therapy Oncology Group 2 vs 3), was a significant predictor of disease specific and overall survival for intermediate/high risk patients and intermediate/high risk with 15% or less risk for metastases. CONCLUSIONS: We combined a risk group stratification scheme for disease specific survival with a nomogram predicting the risk of metastases and created a model that may be useful for designing phase III trials with metastases and disease specific survival as study end points.

Clinical Trials as Topic↗

PubMed2004

Management of prostate-specific antigen relapse in prostate cancer: a European Consensus.

A European Consensus on the management of prostate-specific antigen (PSA) relapse in patients with prostate cancer has been formulated. The key recommendations proposed are that total PSA is the best detection tool for prostate cancer, with free and complexed PSA having a role in the PSA range 1-4 ng/ml. PSA relapse after radical prostatectomy (RP) has been defined as a value of 0.2 ng/ml with one subsequent rise, while the ASTRO definition should be used after radiotherapy. A PSA level of less than 0.4 ng/ml after hormonal therapy can be considered an indicator of a positive response. Continuous assessment using nomograms or artificial neural networks will help to determine whether progression after local therapy is distant or local, which is the basis for treatment decisions. Secondary treatment after local failure of RP should be initiated when PSA levels reach 1.0-1.5 ng/ml and salvage radiotherapy can be considered with or without hormonal therapy. Local failure after radiotherapy can be treated with a choice of high-intensity-focused ultrasound, salvage RP (only in highly selected patients), cryotherapy or external beam radiation. Treatment of distant failure involves hormonal manipulation, the type and the timing of which is based on both physician and patient preferences.

Antineoplastic Agents, Hormonal↗

PubMed2003

[Can nomograms derived in the U.S. applied to German patients? A study about the validation of preoperative nomograms predicting the risk of recurrence after radical prostatectomy].

In patients suffering from prostate cancer, preoperative nomograms, which predict the risk of recurrence may provide a helpful tool in regard to the counselling and planning of an appropriate therapy. The best known nomograms were published by the Baylor College of Medicine, Houston and the Harvard Medical School, Boston. We investigated these nomograms derived in the U.S. when applied to German patients. Data from 1003 patients who underwent radical prostatectomy at the University-Hospital Hamburg were used for validation. Nomogram predictions of the probability for 2-years (Harvard nomogram) and 5-years (Kattan nomogram) freedom from PSA recurrence were compared with actual follow-up recurrence data using areas under the receiver-operating-characteristic curves (AUC). The recurrence free survival after 2 and 5 years was 78% and 58%, respectively. The AUC of the Harvard nomogram predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction of 0.83. Thereby, the Kattan nomogram showed a significant higher predictive accuracy (p=0.0274). For that reason preoperative nomograms derived in the U.S. can be applied to german patients. However, we would recommend the utilization of the Kattan nomogram due to its higher predictive accuracy.

Biomarkers, Tumor↗

PubMed2001

Preoperative plasma levels of transforming growth factor beta(1) strongly predict clinical outcome in patients with bladder carcinoma.

BACKGROUND: Elevated local and circulating levels of transforming growth factor (TGF)-beta(1) have been associated with cancer invasion, progression, and metastasis. The authors tested the hypothesis that preoperative plasma TGF-beta(1) levels would independently predict cancer stage and prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder. METHODS: The study group consisted of 51 patients who underwent radical cystectomy for muscle-invasive or intravesical immuno- and/or chemotherapy refractory Tis, Ta, or T1 TCC (median follow-up, 45.7 months). Preoperative plasma levels of TGF-beta(1) were measured and correlated with pathologic features and clinical outcome. Transforming growth factor-beta(1) levels also were measured in 44 healthy men without any cancer. RESULTS: The mean preoperative plasma TGF-beta(1) level in patients who eventually developed metastases to distant (11.9 +/- 0.9 ng/mL) or regional (9.6 +/- 2.4 ng/mL) lymph nodes was significantly higher than that in patients with nonmetastatic muscle-invasive TCC (5.4 +/- 1.1 ng/mL), which, in turn, was significantly higher than that in patients with nonmetastatic Tis, Ta, or T1 TCC (4.5 +/- 1.2 ng/mL) and healthy subjects (4.5 +/- 1.2 ng/mL; P < 0.001). Preoperative plasma TGF-beta(1) level was an independent predictor of lymphovascular invasion (P = 0.002), metastases to lymph nodes (P = 0.030), disease recurrence (P = 0.009), and disease specific survival (P = 0.015). In a subgroup of patients with muscle-invasive TCC, TGF-beta(1) level was associated with disease recurrence (P = 0.005) and death from bladder carcinoma (P = 0.001). CONCLUSIONS: The authors confirm that plasma TGF-beta(1) levels are elevated in patients with muscle-invasive TCC before cystectomy. Transforming growth factor-beta(1) levels are highest in patients with bladder carcinoma metastatic to lymph nodes and are a strong independent predictor of disease recurrence and disease specific mortality.

Adult↗

PubMed2001

Potency after permanent prostate brachytherapy for localized prostate cancer.

PURPOSE: The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy of sildenafil were studied. METHODS AND MATERIALS: This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated with sildenafil were evaluated as to its efficacy. RESULTS: The median follow-up of this cohort was 34 months (6--92), with a median age of 68 years (47--80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p = 0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p = 0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p = 0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response to sildenafil was significantly better in those patients not treated with NAAD (p = 0.04). CONCLUSIONS: The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who received sildenafil exhibited improved potency in a majority of cases.

Adenocarcinoma↗

PubMed2001

Preoperative plasma levels of transforming growth factor beta(1) (TGF-beta(1)) strongly predict progression in patients undergoing radical prostatectomy.

PURPOSE: Elevated local and circulating levels of transforming growth factor beta(1) (TGF-beta(1)) have been associated with prostate cancer invasion and metastasis. We tested the hypothesis that preoperative plasma TGF-beta(1) levels would independently predict cancer stage and prognosis in patients who undergo radical prostatectomy. PATIENTS AND METHODS: The study group consisted of 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer (median follow-up, 53.8 months). Preoperative plasma levels of TGF-beta(1) were measured and correlated with pathologic parameters and clinical outcomes. TGF-beta(1) levels also were measured in 44 healthy men without cancer, in 19 men with prostate cancer metastatic to regional lymph nodes, and in 10 men with prostate cancer metastatic to bone. RESULTS: Plasma TGF-beta(1) levels in patients with lymph node metastases (14.2 +/- 2.6 ng/mL) and bone metastases (15.5 +/- 2.4 ng/mL) were higher than those in radical prostatectomy patients (5.2 +/- 1.3 ng/mL) and healthy subjects (4.5 +/- 1.2 ng/mL) (P <.001). In a preoperative analysis, preoperative plasma TGF-beta(1) level and biopsy Gleason sum both were predictors of organ-confined disease (P =.006 and P =.006, respectively) and PSA progression (P <.001 and P =.021, respectively). In a postoperative multivariate analysis, preoperative plasma TGF-beta(1) level, pathologic Gleason sum, and surgical margin status were predictors of PSA progression (P =.020,P =.020, and P =.022, respectively). In patients who progressed, preoperative plasma TGF-beta(1) levels were higher in those with presumed distant compared with local-only failure (P =.019). CONCLUSION: Plasma TGF-beta(1) levels are markedly elevated in men with prostate cancer metastatic to regional lymph nodes and bone. In men without clinical or pathologic evidence of metastases, the preoperative plasma TGF-beta(1) level is a strong predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.

Adult↗

PubMed2001

Prediction of response to salvage radiation therapy in patients with prostate cancer recurrence after radical prostatectomy.

PURPOSE: To identify factors predictive of local recurrence as defined by a complete response to salvage radiation therapy in patients whose disease recurs after radical prostatectomy. PATIENTS AND METHODS: Ninety-five patients with recurrence after radical prostatectomy who were evaluated by prostatic fossa biopsies, and a subset of 49 of these patients treated with radiation for control of presumed or biopsy-proven local recurrence, were studied. RESULTS: Biopsies were positive in 40 (42%) of the 95 biopsied patients. Multivariate analysis revealed that prebiopsy prostate-specific antigen (PSA) level, postrecurrence PSA doubling time, and positive digital rectal examination (DRE) of the prostatic fossa were all statistically significant predictors of a positive biopsy. For the 49 patients subsequently treated with salvage radiation therapy, the overall actuarial 3- and 5-year PSA relapse-free probabilities were 43% and 24%, respectively. Univariate analysis showed no differences in the PSA relapse-free probabilities associated with any pathologic features of the radical prostatectomy specimen, biopsy confirmation of local recurrence, or DRE of the prostatic fossa. In multivariate analysis, controlling for all other variables, preradiation PSA and postrecurrence PSA doubling time measured before radiation were the only statistically significant predictors of outcome. CONCLUSION: DRE of the prostatic fossa, prebiopsy PSA, and postrecurrence PSA doubling time predict which patients will have biopsy-proven local recurrence. However, response to salvage radiation therapy is associated with postrecurrence PSA doubling time and with preradiation PSA level only. DRE of the prostatic fossa and biopsy confirmation of local recurrence are not associated with salvage radiation outcome.

Aged↗

PubMed2001

Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer.

OBJECTIVES: To develop a prognostic nomogram to predict the freedom from recurrence for patients treated with permanent prostate brachytherapy for localized prostate cancer. METHODS: We performed a retrospective analysis of 920 patients treated with permanent prostate brachytherapy between 1992 and 2000. The clinical parameters included clinical stage, biopsy Gleason sum, pretreatment prostate-specific antigen (PSA) value, and administration of external beam radiation. Patients who received neoadjuvant androgen deprivation therapy were excluded. Failure was defined as any post-treatment administration of androgen deprivation, clinical relapse, or biochemical failure, defined as three PSA rises. Patients with fewer than three PSA rises were censored at the time of the first PSA rise. Data from two outside institutions served as validation. RESULTS: A nomogram that predicts the probability of remaining free from biochemical recurrence for 5 years after brachytherapy without adjuvant hormonal therapy was developed using Cox proportional hazards regression analysis. External validation revealed a concordance index of 0.61 to 0.64, and calibration of the nomogram suggested confidence limits of +5% to -30%. CONCLUSIONS: The pretreatment nomogram we developed may be useful to physicians and patients in estimating the probability of successful treatment 5 years after brachytherapy for clinically localized prostate cancer.

Adenocarcinoma↗

PubMed2001

Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis.

OBJECTIVES: Elevated circulating levels of interleukin 6 (IL-6) have been associated with cancer metastasis. IL-6 binds either to membrane or to soluble IL-6 receptor (IL-6sR), which then induces homodimerization of gp130 that activates downstream signaling. We tested the hypothesis that preoperative plasma IL-6 and IL-6sR levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy. METHODS: Plasma levels of IL-6 and IL-6sR were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone. RESULTS: Plasma IL-6 and IL-6sR levels were highest in patients with bone metastases (P <0.001). The preoperative IL-6 and IL-6sR levels were associated with the preoperative prostate-specific antigen (PSA) level (P </=0.041), prostatectomy tumor volume (P </=0.048), and final Gleason sum (P </=0.042). The preoperative IL-6 and IL-6sR levels and biopsy Gleason sum were independent predictors of PSA progression (P </=0.029). However, in a model that included both IL-6 and IL-6sR, only IL-6sR and the biopsy Gleason sum predicted progression (P </=0.040). In patients whose disease progressed, the preoperative IL-6 and IL-6sR levels were highest in those with presumed aggressive failure (P </=0.042). CONCLUSIONS: Plasma IL-6 and IL-6sR levels were dramatically elevated in the men with prostate cancer metastatic to bone. In patients with clinically localized prostate cancer, the preoperative plasma IL-6 and IL-6sR levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.

Adult↗

PubMed2001

Prognostic significance of the diameter of perineural invasion in radical prostatectomy specimens.

We assessed whether the quantification of cancer invasion into the perineural space influences the prognosis of patients treated with radical prostatectomy. We conducted a retrospective study of clinical and pathologic features in 640 consecutive patients with clinical stage Tla-T3bNXM0 prostate cancer who were treated with radical retropubic prostatectomy by the same surgeon between 1989 and 1995. None had received preoperative hormonal therapy or radiotherapy. Detailed pathologic analysis, including the presence and maximum diameter of perineural invasion (PNI), was performed by 2 pathologists. Treatment failure was defined as either a serum prostate-specific antigen (PSA) level > 0.4 ng/mL and rising or initiation of adjuvant therapy. The median follow-up time was 48 months (range, 1 to 111 months). Overall, PNI was detected in 477 patients (75%). The progression-free 5-year probability rate after prostatectomy for patients with PNI was 70% +/- 3% compared with 94% +/- 2% for patients without PNI (P <.001). The mere presence of PNI was not an independent predictor of progression in a Cox proportional hazards analysis when the other established prognostic factors (serum PSA level, pathologic stage, surgical margin, and tumor volume) were considered. However, the increasing diameter of the largest focus of PNI was strongly associated with other established prognostic factors and the probability of progression after radical prostatectomy. Although little adverse effect in patients with PNI < 0.25 mm was seen 5 years after surgery, those with a PNI diameter of 0.25 to 0.5 mm were significantly (P <.001) less likely to remain free of progression; only 36% of those with PNI of 0.5 to 0.75 mm (P <.001) and 14% of those with PNI > or =0.75 mm (P =.002) were free of progression. In a Cox proportional hazard analysis, the PNI diameter was an independent predictor of prognosis. These results support that the measurement of the PNI diameter, easily recorded from prostatectomy specimens, could add important information to the prognosis of prostate cancer patients. Controversy regarding the significance of PNI may result from the lack of quantitative assessment of PNI in previous studies.

Adenocarcinoma↗

PubMed2001

Primary Gleason pattern as a predictor of disease progression in gleason score 7 prostate cancer: a multivariate analysis of 823 men treated with radical prostatectomy.

Gleason score (GS) is a powerful predictor of disease progression in men with prostate cancer (PCa). The majority of clinically localized prostate cancers, however, are moderately (GS5/6) or moderate to poorly (GS7) differentiated tumors with indeterminate prognosis. Differences in disease progression between patients with GS5/6 and GS7 tumors suggest the presence of any component of high-grade tumor (Gleason pattern [GP] 4/5) worsens prognosis markedly. Indeed, McNeal et al. have shown that quantification of GP4/5 provides prognostic information beyond the standard GS. Few investigators have analyzed whether primary and secondary GPs are important prognostically within GS7 PCa. All 823 whole-mount radical prostatectomy specimens with GS7 from a single surgeon (P.T.S.) were analyzed. Tumors were either 3+4 or 4+3, and primary GP was assigned by the same pathologist (T.M.W.). A total of 643 patients with 3+4 tumors and 180 patients with 4+3 tumors were studied. Statistical analysis using the log-rank test showed a significant difference in recurrence-free survival between patients with primary GP4 and those with GP3 (p <0.0001). However, in multivariate analysis with preoperative prostate-specific antigen, total tumor volume, surgical margin status, and the presence or absence of seminal vesicle involvement, extraprostatic extension, and lymph node metastasis, the primary GP did not retain independent significance (p = 0.0557). GS7 PCa is a heterogeneous group of tumors. In this cohort of men with GS7 tumors treated by radical retropubic prostatectomy, primary GP showed a significant correlation with other histologic and clinical predictors of disease progression; however, it was not independently predictive of disease progression in multivariate analysis (p = 0.76).

Adenocarcinoma↗

PubMed2001

Incidence, location, and significance of periprostatic and periseminal vesicle lymph nodes in prostate cancer.

Pelvic lymph node metastases in prostate cancer (PCa) carry an ominous prognosis. Periprostatic/periseminal vesicle (PP/PSV) lymph nodes are present in some individuals, but their incidence and involvement by metastases are unknown. A total of 832 of 1233 (67.5%) patients who underwent radical retropubic prostatectomy for clinically localized PCa at the Methodist Hospital from 1983 to 1998 by one surgeon (P.T.S.) had whole-mount slides available for review. Of these, 92 (11.1%) had received preoperative therapy (radiation in 48 [5.8%], hormonal in 44 [5.3%]). Slides were examined with the naked eye by placing them on a white illuminated background, and any area suggestive of a lymph node in PP/PSV fat was confirmed microscopically and assessed for the presence of metastases. Thirty-seven of 832 patients (4.4%) had 39 PP/PSV lymph nodes-one bilateral, one with two ipsilateral lymph nodes, and the rest solitary. Sizes ranged from 0.7 to 4.5 mm (mean 1.8 mm). Distribution was 2 of 39 (5.1%) apical, 3 of 39 (7.7%) mid, 17 of 39 (43.6%) base, and 17 of 39 (43.6%) seminal vesicle. Five patients (0.6%) had metastatic PCa to the PP/PSV lymph nodes. All five patients were of advanced pathologic T stage [one pT3a (extraprostatic extension) and four pT3b (seminal vesicle invasion)]. Only two of those five (40%) had metastases (all ipsilateral) to pelvic lymph nodes. In three of five (60%) the metastases were isolated to the PP/PSV lymph nodes. Metastases were to the lymph nodes in the periseminal vesicle fat in four of five (80%) of the cases and in the fat surrounding the base of the prostate in one of five (20%). Four of five (80%) patients recurred. Histologic grade (Gleason score), tumor volume, and failure (recurrence) rates were significantly different between the five patients with metastases and the 32 patients without metastases to the PP/PSV lymph nodes (p <0.0001, p <0.0001, and p = 0.005, respectively). However, there was no evidence that an individual patient's probability of having a PP/PSV lymph node increased with resection of the neurovascular bundle (p = 0.7698). PP/PSV lymph nodes are uncommon, but based upon these limited data, it appears that patients with metastases limited to PP/PSV lymph nodes have a poor prognosis (similar to pelvic lymph node metastases) and should be included in the American Joint Committee on Cancer (AJCC) Staging Manual to indicate "N1" if positive for metastases.

Adenocarcinoma↗

PubMed2001

E-cadherin immunostaining of bladder transitional cell carcinoma, carcinoma in situ and lymph node metastases with long-term followup.

PURPOSE: We analyze the expression of E-cadherin in bladder transitional cell carcinoma, areas of carcinoma in situ and lymph node metastases, and determine the value of E-cadherin immunoreactivity for predicting disease progression and survival of patients with bladder transitional cell carcinoma. MATERIALS AND METHODS: The study group consisted of 77 patients who underwent radical cystectomy. Formalin fixed paraffin sections were processed with a hot, citric acid antigen retrieval method, followed by immunostaining with anti-E-cadherin monoclonal antibody and a standard avidin biotin complex technique. E-cadherin expression was also evaluated in carcinoma in situ sections (18) and in regional lymph node metastases (17). RESULTS: Loss of normal membrane E-cadherin immunoreactivity was found in 59 (77%) patients. Abnormal expression of E-cadherin was associated with muscle invasive disease (p = 0.010) and lymph node metastasis (p = 0.044). Of the 18 carcinoma in situ specimens 15 (83%) and of the 17 metastatic lymph nodes 13 (76%) had abnormal E-cadherin expression. Concordance rates of E-cadherin status in carcinoma in situ areas and metastatic lymph nodes with the primary tumors were 85% and 88%, respectively. At a median followup of 128 months, abnormal E-cadherin expression was significantly associated with disease progression (p = 0.0219) and bladder cancer specific survival (p = 0.037). E-cadherin expression and pathological stage but not grade were independent predictors of disease progression (p = 0.042, 0.047 and 0.158, respectively). CONCLUSIONS: In bladder cancer altered E-cadherin expression is associated with the degree of invasiveness, lymph node metastasis and increased risk of death from bladder cancer. Furthermore, E-cadherin status is an independent predictor of disease progression in patients treated with cystectomy for transitional cell carcinoma of the bladder.

Aged↗

PubMed2001

A catalog of prostate cancer nomograms.

PURPOSE: Prediction is central to the management of prostate cancer. Nomograms are devices that make predictions. We organized many nomograms for prostate cancer. MATERIALS AND METHODS: Using MEDLINE a literature search was performed on prostate cancer nomograms from January 1966 to February 2000. We recorded input variables, prediction form, the number of patients used to develop the nomogram and the outcome being predicted. We also recorded the accuracy measures reported by the original authors and whether the nomograms have withstood validation. In addition, we noted whether the nomograms were proprietary or in the public domain. Each nomogram was classified into patient clinical disease state and the outcome being predicted. RESULTS: The literature search generated 42 published nomograms that may be applied to patients in various clinical stages of disease. Of the 42 nomograms only 18 had undergone validation, of which 2 partially failed. Few nomograms have been compared for predictive superiority and none appears to have been compared with clinical judgment alone. CONCLUSIONS: Patients with prostate cancer need accurate predictions. Prognostic nomograms are available for many clinical states and outcomes, and may provide the most accurate predictions currently available. Selection among them and progress in this field are hampered by the lack of comparisons for predictive accuracy.

Biopsy↗

PubMed2001

A postoperative prognostic nomogram for renal cell carcinoma.

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.

Carcinoma, Renal Cell↗

PubMed2001

Time trade-off utility modified to accommodate degenerative and life-threatening conditions.

The time trade-off is often argued to be the preferred utility assessment method. When measuring current health in its classic form, it involves a comparison of two certainties: perfect health and current health, each for a fixed period of time and followed by death. This makes the time trade-off insensitive to patient fears regarding premature death or worsening health. We suggest the classic time trade-off be modified to include subjective rather than actuarial life expectancy, and relaxation of the current health option to include uncertainty in quantity and quality of life. We illustrate the mechanics of this modified time trade-off and report a preliminary application to 122 men presenting to a prostate cancer screening program. Further analysis of this modified time trade-off appears warranted.

Attitude to Health↗