Classifying cancer pathology reports with hierarchical self-attention networks.

We introduce a deep learning architecture, hierarchical self-attention networks (HiSANs), designed for classifying pathology reports and show how its unique architecture leads to a new state-of-the-art in accuracy, faster training, and clear interpretability. We evaluate performance on a corpus of 374,899 pathology reports obtained from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Each pathology report is associated with five clinical classification tasks - site, laterality, behavior, histology, and grade. We compare the performance of the HiSAN against other machine learning and deep learning approaches commonly used on medical text data - Naive Bayes, logistic regression, convolutional neural networks, and hierarchical attention networks (the previous state-of-the-art). We show that HiSANs are superior to other machine learning and deep learning text classifiers in both accuracy and macro F-score across all five classification tasks. Compared to the previous state-of-the-art, hierarchical attention networks, HiSANs not only are an order of magnitude faster to train, but also achieve about 1% better relative accuracy and 5% better relative macro F-score.

Scalable deep text comprehension for Cancer surveillance on high-performance computing.

BACKGROUND: Deep Learning (DL) has advanced the state-of-the-art capabilities in bioinformatics applications which has resulted in trends of increasingly sophisticated and computationally demanding models trained by larger and larger data sets. This vastly increased computational demand challenges the feasibility of conducting cutting-edge research. One solution is to distribute the vast computational workload across multiple computing cluster nodes with data parallelism algorithms. In this study, we used a High-Performance Computing environment and implemented the Downpour Stochastic Gradient Descent algorithm for data parallelism to train a Convolutional Neural Network (CNN) for the natural language processing task of information extraction from a massive dataset of cancer pathology reports. We evaluated the scalability improvements using data parallelism training and the Titan supercomputer at Oak Ridge Leadership Computing Facility. To evaluate scalability, we used different numbers of worker nodes and performed a set of experiments comparing the effects of different training batch sizes and optimizer functions. RESULTS: We found that Adadelta would consistently converge at a lower validation loss, though requiring over twice as many training epochs as the fastest converging optimizer, RMSProp. The Adam optimizer consistently achieved a close 2nd place minimum validation loss significantly faster; using a batch size of 16 and 32 allowed the network to converge in only 4.5 training epochs. CONCLUSIONS: We demonstrated that the networked training process is scalable across multiple compute nodes communicating with message passing interface while achieving higher classification accuracy compared to a traditional machine learning algorithm.

Deep Learning for Automated Extraction of Primary Sites From Cancer Pathology Reports.

Pathology reports are a primary source of information for cancer registries which process high volumes of free-text reports annually. Information extraction and coding is a manual, labor-intensive process. In this study, we investigated deep learning and a convolutional neural network (CNN), for extracting ICD-O-3 topographic codes from a corpus of breast and lung cancer pathology reports. We performed two experiments, using a CNN and a more conventional term frequency vector approach, to assess the effects of class prevalence and inter-class transfer learning. The experiments were based on a set of 942 pathology reports with human expert annotations as the gold standard. CNN performance was compared against a more conventional term frequency vector space approach. We observed that the deep learning models consistently outperformed the conventional approaches in the class prevalence experiment, resulting in micro- and macro-F score increases of up to 0.132 and 0.226, respectively, when class labels were well populated. Specifically, the best performing CNN achieved a micro-F score of 0.722 over 12 ICD-O-3 topography codes. Transfer learning provided a consistent but modest performance boost for the deep learning methods but trends were contingent on the CNN method and cancer site. These encouraging results demonstrate the potential of deep learning for automated abstraction of pathology reports.

Hierarchical attention networks for information extraction from cancer pathology reports.

OBJECTIVE: We explored how a deep learning (DL) approach based on hierarchical attention networks (HANs) can improve model performance for multiple information extraction tasks from unstructured cancer pathology reports compared to conventional methods that do not sufficiently capture syntactic and semantic contexts from free-text documents. MATERIALS AND METHODS: Data for our analyses were obtained from 942 deidentified pathology reports collected by the National Cancer Institute Surveillance, Epidemiology, and End Results program. The HAN was implemented for 2 information extraction tasks: (1) primary site, matched to 12 International Classification of Diseases for Oncology topography codes (7 breast, 5 lung primary sites), and (2) histological grade classification, matched to G1-G4. Model performance metrics were compared to conventional machine learning (ML) approaches including naive Bayes, logistic regression, support vector machine, random forest, and extreme gradient boosting, and other DL models, including a recurrent neural network (RNN), a recurrent neural network with attention (RNN w/A), and a convolutional neural network. RESULTS: Our results demonstrate that for both information tasks, HAN performed significantly better compared to the conventional ML and DL techniques. In particular, across the 2 tasks, the mean micro and macro F-scores for the HAN with pretraining were (0.852,0.708), compared to naive Bayes (0.518, 0.213), logistic regression (0.682, 0.453), support vector machine (0.634, 0.434), random forest (0.698, 0.508), extreme gradient boosting (0.696, 0.522), RNN (0.505, 0.301), RNN w/A (0.637, 0.471), and convolutional neural network (0.714, 0.460). CONCLUSIONS: HAN-based DL models show promise in information abstraction tasks within unstructured clinical pathology reports.

Designing a public square for research computing.

A set of principles is proposed for sponsors and developers of research computing applications that can increase the likelihood of successful adoption by researchers.

Evaluation of prediagnostic prostate-specific antigen dynamics as predictors of death from prostate cancer in patients treated conservatively.

Prostate-specific antigen (PSA) dynamics have been proposed to predict outcome in men with prostate cancer. We assessed the value of PSA velocity (PSAV) and PSA doubling time (PSADT) for predicting prostate cancer-specific mortality (PCSM) in men with clinically localized prostate cancer undergoing conservative management or early hormonal therapy. From 1990 to 1996, 2,333 patients were identified, of whom 594 had two or more PSA values before diagnosis. We examined 12 definitions for PSADT and 10 for PSAV. Because each definition required PSA measurements at particular intervals, the number of patients eligible for each definition varied from 40 to 594 and number of events from 10 to 119. Four PSAV definitions, but no PSADT, were significantly associated with PCSM after adjustment for PSA in multivariable Cox proportional hazards regression. All four could be calculated only for a proportion of events, and the enhancements in predictive accuracy associated with PSAV had very wide confidence intervals. There was no clear benefit of PSAV in men with low PSA and Gleason grade 6 or less. Although evidence that certain PSAV definitions help to predict PCSM in the cohort exist, the value of incorporating PSAV in predictive models to assist in determining eligibility for conservative management is, at best, uncertain.

Postoperative nomogram predicting the 9-year probability of prostate cancer recurrence after permanent prostate brachytherapy using radiation dose as a prognostic variable.

PURPOSE: To report a multi-institutional outcomes study on permanent prostate brachytherapy (PPB) to 9 years that includes postimplant dosimetry, to develop a postimplant nomogram predicting biochemical freedom from recurrence. METHODS AND MATERIALS: Cox regression analysis was used to model the clinical information for 5,931 patients who underwent PPB for clinically localized prostate cancer from six centers. The model was validated against the dataset using bootstrapping. Disease progression was determined using the Phoenix definition. The biological equivalent dose was calculated from the minimum dose to 90% of the prostate volume (D90) and external-beam radiotherapy dose using an alpha/beta of 2. RESULTS: The 9-year biochemical freedom from recurrence probability for the modeling set was 77% (95% confidence interval, 73-81%). In the model, prostate-specific antigen, Gleason sum, isotope, external beam radiation, year of treatment, and D90 were associated with recurrence (each p < 0.05), whereas clinical stage was not. The concordance index of the model was 0.710. CONCLUSION: A predictive model for a postimplant nomogram for prostate cancer recurrence at 9-years after PPB has been developed and validated from a large multi-institutional database. This study also demonstrates the significance of implant dosimetry for predicting outcome. Unique to predictive models, these nomograms may be used a priori to calculate a D90 that likely achieves a desired outcome with further validation. Thus, a personalized dose prescription can potentially be calculated for each patient.

Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy.

PURPOSE: Controversy exists as to whether current pretreatment prostate-specific antigen (PSA) dynamics enhance outcome prediction in patients undergoing treatment for prostate cancer. We assessed whether pretreatment PSA velocity (PSAV) or doubling time (PSADT) predicted outcome in men undergoing radical prostatectomy and whether any definition enhanced accuracy of an outcome prediction model. PATIENTS AND METHODS: The cohort included 2,938 patients with two or more PSA values before radical prostatectomy. Biochemical recurrence (BCR) occurred in 384 patients, and metastases occurred in 63 patients. Median follow-up for patients without BCR was 2.1 years. We used univariate Cox proportional hazards regression to evaluate associations between published definitions of PSADT and PSAV with BCR and metastasis. Predictive accuracy was assessed using the concordance index. RESULTS: On univariate analysis, two of 12 PSADT and four of 10 PSAV definitions were univariately associated with both BCR and metastasis (P < .05). One PSADT and one PSAV definition had a higher predictive accuracy for BCR over PSA alone, and four PSAV definitions improved prediction of metastasis. However, the improvements in predictive accuracy were small, associated with wide CIs, and markedly reduced if additional predictors of stage and grade were included alongside PSA. Modeling with random variables suggests that similar results would be expected by chance. CONCLUSION We found no clear evidence that any definition of PSA dynamics substantially enhances the predictive accuracy of a single pretreatment PSA alone.

Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.

PURPOSE: To investigate the biochemical control rates and survival for Gleason score 7-10 prostate cancer patients undergoing permanent prostate brachytherapy as a function of the biologic effective dose (BED). METHODS AND MATERIALS: Six centers provided data on 5,889 permanent prostate brachytherapy patients, of whom 1,078 had Gleason score 7 (n = 845) or Gleason score 8-10 (n = 233) prostate cancer and postimplant dosimetry results available. The median prostate-specific antigen level was 7.5 ng/mL (range, 0.4-300). The median follow-up for censored patients was 46 months (range, 5-130). Short-term hormonal therapy (median duration, 3.9 months) was used in 666 patients (61.8%) and supplemental external beam radiotherapy (EBRT) in 620 (57.5%). The patients were stratified into three BED groups: <200 Gy (n = 645), 200-220 Gy (n = 199), and >220 Gy (n = 234). Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. RESULTS: The 5-year bFFF rate was 80%. The bFFF rate stratified by the three BED groups was 76.4%, 83.5%, and 88.3% (p < 0.001), respectively. Cox regression analysis revealed Gleason score, prostate-specific antigen level, use of hormonal therapy, EBRT, and BED were associated with bFFF (p < 0.001). Freedom from metastasis improved from 92% to 99% with the greatest doses. The overall survival rate at 5 years for the three BED groups for Gleason score 8-10 cancer was 86.6%, 89.4%, and 94.6%, respectively (p = 0.048). CONCLUSION: These data suggest that permanent prostate brachytherapy combined with EBRT and hormonal therapy yields excellent bFFF and survival results in Gleason score 7-10 patients when the delivered BEDs are >220 Gy. These doses can be achieved by a combination of 45-Gy EBRT with a minimal dose received by 90% of the target volume of 120 Gy of (103)Pd or 130 Gy of (125)I.

Customized dose prescription for permanent prostate brachytherapy: insights from a multicenter analysis of dosimetry outcomes.

PURPOSE: To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group. METHODS AND MATERIALS: Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. (125)I was used in 2,293 (58%), (103)Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140-200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log-rank test. RESULTS: The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). CONCLUSIONS: These data suggest that permanent brachytherapy dose prescriptions can be customized to risk status. In low-risk patients, achieving a BED of >or=140 Gy might be adequate for prostate-specific antigen control. However, high-risk disease might require a BED dose of >or=200 Gy.

Evaluation of postradiotherapy PSA patterns and correlation with 10-year disease free survival outcomes for prostate cancer.

PURPOSE: To describe the prostate-specific antigen (PSA) pattern profiles observed after external beam radiotherapy with and without short-term neoadjuvant androgen deprivation therapy (ST-ADT) and to report the association of established posttreatment PSA patterns with long-term disease-free survival outcomes. METHODS AND MATERIALS: A total of 1,665 patients were treated with conformal external beam radiotherapy for clinically localized prostate cancer. Of 570 patients who had the requisite>10 consecutive PSA measurements for statistical analysis, 194 patients received a median of 3 months of ADT before radiotherapy and 376 were treated with radiotherapy alone. The median follow up was 103 months. RESULTS: In the group treated with ST-ADT, three distinct postradiotherapy PSA patterns were identified: a stable trend (44%), an increasing trend followed by stabilization of the PSA (25%), and an increasing trend (31%). Among the subgroup that demonstrated a rising and subsequent stabilizing patterns, PSA levels had gradually risen to a median value of 0.9 ng/mL after therapy, stabilized, and remained durably suppressed. The only identified trends among patients treated with external beam radiotherapy without ST-ADT were declining PSA levels followed by stable PSA trends or declining patterns followed by rising levels. Patients whose PSA levels stabilized after an initial rise or those with slowly rising PSA profiles had a lower incidence of distant metastasis compared to those with accelerated rises after therapy. CONCLUSIONS: For those treated with external beam radiotherapy in conjunction with ST-ADT, a significant percentage who develop a rising PSA after treatment are expected to manifest subsequent stabilization at plateaued levels of approximately 1.0 ng/mL, which can remain durably suppressed. The likelihood of distant metastasis in these patients is low despite the PSA stabilization at levels 1.0 ng/mL or higher and comparable to outcomes observed for those with lower nonrising PSA values.

Cancer-specific survival and predictors of prostate-specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy.

BACKGROUND: The objectives of the current study were to determine the long-term biochemical recurrence (BCR) and cancer-specific survival (CSS) rates for men with seminal vesicle invasion (SVI) and to identify risk factors for freedom from BCR and CSS in patients who received treatment in the prostate-specific antigen era and who had SVI identified at the time of radical prostatectomy (RP). METHODS: Prospective clinical, pathologic, and outcome data were collected for 5377 men who underwent RP between June 1983 and August 2004. There were 936 patients who were excluded because they received treatment before RP. Multivariable analysis was used to identify the factors that predicted BCR and CSS. RESULTS: Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91 of those 387 patients (24%) had lymph node involvement (LNI). In total, 210 patients experienced BCR. For patients without LNI, the 10-year and 15-year freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10-year BCR-free probability was 10%, but the 10-year CSS probability was 74%. By 10 years, patients with LNI were 3 times more likely to die from cancer than from other causes; nonetheless, 66% of patients were alive despite their advanced stage. The preoperative prostate-specific antigen level, extracapsular extension, LNI, and Gleason grade were associated independently with BCR. Gleason scores of 8 to 10 and LNI were significant predictors of CSS. CONCLUSIONS: SVI does not invariably signal BCR or death from cancer in patients who undergo RP and pelvic lymph node dissection. Fifteen years later, approximately 33% of men with SVI and negative lymph nodes are expected remain free of BCR, and CSS was surprisingly good.

Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy.

An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy.

The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer.

PURPOSE: We examined the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed 5,038 consecutive patients who underwent radical retropubic prostatectomy between 1983 and 2003. Clinicopathological parameters, including the administration of neoadjuvant hormonal therapy, preoperative prostate specific antigen, specimen Gleason score, surgeon and pathological stage, were collected prospectively in our prostate cancer database. We excluded men treated with radiation or chemotherapy before surgery. BCR was defined as 2 postoperative prostate specific antigen increases greater than 0.2 ng/ml. Cox models were used to determine whether the number of nodes removed or the number of positive nodes predicted freedom from BCR after adjustment for prognostic covariates. RESULTS: The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p = 0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p <0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p = 0.01). CONCLUSIONS: Nodal disease increased the risk of progression. Extensive lymphadenectomy enhances the accuracy of surgical staging. However, we were unable to determine that removing more nodes improves freedom from BCR uniformly. Since the proportion of patients with prostate cancer with positive nodes is low, the value of extensive lymphadenectomy requires a multi-institutional, randomized clinical trial.

Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy.

PURPOSE: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. METHODS AND MATERIALS: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). RESULTS: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of <4, 4-10, and >10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. CONCLUSIONS: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent disease.

Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer.

PURPOSE: To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy. RESULTS: The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months. CONCLUSION: In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.

Morbidity and functional outcomes of salvage radical prostatectomy for locally recurrent prostate cancer after radiation therapy.

PURPOSE: Few patients with locally recurrent prostate cancer after external beam (EB) or interstitial (I) radiotherapy (RT) are considered candidates for salvage radical prostatectomy (RP) due to high reported rates of major complications and urinary incontinence. We report the morbidity associated with salvage RP in 100 consecutive patients. MATERIALS AND METHODS: From 1984 to 2003 salvage RP was performed for recurrent prostate cancer following EBRT in 58 cases, and IRT in 42 (28 retropubic) and (14 transperineal). Clinical information was obtained from a prospective database. RESULTS: Since 1993, the major complication rate has decreased significantly (13% vs 33%, p = 0.02), including the rectal injury rate (2% vs 15%, p = 0.01). Compared with retropubic IRT and/or pre-radiotherapy pelvic lymph node dissection the risk of major complications following EBRT or transperineal IRT was significantly less (OR 0.2, p = 0.006). At 5 years an estimated 39% of patients were dry and 68% required 1 pad daily or less. A total of 23 patients with moderate-severe incontinence underwent artificial sphincter placement. The anastomotic stricture rate was 30%. The 5-year potency rate was 28% following unilateral or bilateral nerve sparing RP and 45% in previously potent patients. CONCLUSIONS: Due to patient selection the major complication rate after salvage RP has improved significantly with time and it is similar to that of standard RP. Rates of anastomotic stricture and moderate to severe incontinence are higher than those observed after standard RP. However, most patients recover reasonable urinary continence and a substantial number of select patients recover potency. The acceptable morbidity profile of salvage RP following EBRT and transperineal IRT should persuade more physicians to consider patients for this potentially curative procedure.

Conventional (clear cell) renal carcinoma metastases have greater bcl-2 expression than high-risk primary tumors.

Bcl-2 antagonizes p53-induced apoptosis and may contribute to chemoresistance. In renal cell carcinoma (RCC), the role of bcl-2 is not well-defined, though its expression is reportedly low in primary tumors and lacks prognostic value. This study evaluates patterns of bcl-2 expression in high-risk (pT(3)) primary tumors and in matched patient metastases. Immunohistochemical analysis of bcl-2 was performed on 149 cases of conventional (clear cell) RCC (112 pT(3) primaries, 37 metastases). Paraffin-embedded tissues were obtained from nephrectomies and metastatic resections. Median follow up was 48 months in the entire cohort and 69 months in living patients. We evaluated associations between bcl-2 expression and tumor recurrence or patient survival with the Cox regression test, and used the t-test and Pearson correlation methods to evaluate bcl-2 expression in primary and metastatic cases. Bcl-2 expression was observed at a higher frequency in metastases (21/37 cases; 57%) compared to primary tumors (24/112 cases; 21%; P < 0.001). The percentage of cells stained was greater in metastases than primary tumors (P = 0.003). This finding was also noted when expression in metastatic cases was compared with matched primaries (P = 0.05). Bcl-2 expression did not predict disease-free (P = 0.30), disease-specific (P = 0.90), or overall (P = 0.51) survival. Most RCC primary tumors have low-to-absent levels of bcl-2 protein, whereas most RCC metastases display greater protein levels. Bcl-2 expression in primary tumors does not predict clinical outcome. However, expression of bcl-2 protein occurs at a high frequency in RCC metastases when compared to primary tumors. It may be reasonable to target RCC patients displaying altered bcl-2 levels for molecular therapies, such as anti-bcl2, should metastatic disease develop.

Mode of presentation of renal cell carcinoma provides prognostic information.

PURPOSE: Broadened applications of imaging modalities have increased the incidental detection of renal cell carcinoma (RCC) over the past decade. Previous small series have suggested a prognostic benefit for incidental presentation. This study utilizes a large contemporary patient cohort to examine patterns of RCC presentation and their clinical implications. MATERIALS AND METHODS: Retrospective analysis was performed on 721 patients (260 women, 461 men) who underwent 750 nephrectomies for treatment of RCC between 7/1/89 and 12/31/97; 29 patients required two operations for bilateral RCC. Median age and follow-up were 63 years and 41 months, respectively. Indicators of symptomatic presentation included flank pain, flank mass, hematuria, varicocele, constitutional symptoms, paraneoplastic syndromes, and bone pain related to metastatic disease. Mode of presentation was compared with clinicopathologic parameters using Chi-square and t-test analyses. Survival analysis was performed using Kaplan-Meier estimates (log-rank test) and Cox regression modeling. RESULTS: Incidental and symptomatic presentation occurred in 57% and 42% of cases, respectively. When compared to incidental cases, symptomatic presentation was predominantly detected in younger patients (mean age, 59 years; P < .001), in males (P < .04), and in tumors with conventional (clear cell) histology (P < .001), larger size (mean, 8 cm; P < .001), and non-organ confined pathology (P < .001). In univariate analysis, symptomatic cases had a more adverse disease-free (P < .0001) and disease-specific (P < .0001) survival. In multivariate analysis, mode of presentation was an independent predictor of disease-free (P < 0.0001) and disease-specific survival (P < 0.005). CONCLUSIONS: Symptomatic presentation correlates with an aggressive histology and advanced disease. Incidental tumors may be frequently detected in female and elderly patients, as these groups traditionally seek general medical care more regularly. Mode of presentation can independently predict an adverse patient outcome and should be included in RCC-specific modeling systems.