[Current Status of Prostate Cancer and Its Relation to Home Medical Care].

Because ofboth the indolent and aggressive nature ofprostate cancers, it is not easy to select the best treatment for patients receiving home medical care who already have many diseases. Since the growth ofprostate cancer is generally slow and all treatments adversely affect the quality of life to some degree, conservative treatment may well be the best option for these patients with prostate cancer. However, it is also true that we often encounter home medical care patients with a locally advanced cancer who had symptoms such as difficulty to urine, macrohematuria and/or lumbago. Such patients need to be diagnosed soon and treated with mainly hormonal therapy after consultation with the specialist. Thus, after a careful evaluation ofthe nature ofthe cancer and comorbidity, we need to provide the best option ofdiagnosis and treatment for home medical care patients to maintain their quality of life.

Prognostic Value of Platelet Counts in Patients with Metastatic Prostate Cancer Treated with Endocrine Therapy.

PURPOSE: The endocrine therapy is effective for patients with advanced prostate cancer, but the disease eventually becomes refractory to treatment. The aim of this study was to investigate prognostic factors and to develop a risk stratification model for survival in patients with advanced prostate cancer undergoing endocrine therapy. MATERIALS AND METHODS: This study included 197 patients with stage IV prostate cancer who were treated with endocrine therapy as primary treatment at Tokyo Medical University, Tokyo, Japan, between January 1999 and November 2012. Prognostic values including baseline clinical laboratory values before endocrine therapy for stage IV prostate cancer were examined. Patients (n = 30) who were not followed or for whom data were unavailable or who were treated with radiotherapy were excluded from the study. Excluding these patients, we retrospectively analyzed 167 patients who were treated with endocrine therapy as the primary treatment. Disease-specific survival (DSS) was evaluated using the Kaplan-Meier method, and prognostic factors were identified using the Cox proportional hazard model analysis. RESULTS: In univariate analyses, patients with a performance status (PS) ? 2, platelet count ? 3.0× 105 µ/L, prostate specific antigen (PSA) > 50 ng/mL, alkaline phosphatase (ALP) > 350 U/L, lactate dehydrogenase (LDH) > 240 IU/L, and Gleason score (GS) ? 8, hemoglobin (Hb) < 12 g/dL, extent of disease (EOD) ? 3 and poorly differentiated adenocarcinoma showed significantly lower DSS than their respective counterparts. Neutrophil-to-Lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and white blood cell (WBC) count were not significantly associated with DSS. In a multivariate Cox proportional hazard model, PS and platelet count were independent prognostic factors. Based on the hazard rate (HR) calculated by the following formula: HR = exp (0.82 × PS + 1.38 × platelet count) patients were stratified into 3 risk groups. The differences in DSS rates among the 3 groups were statistically significant. CONCLUSION: These results suggest that PS and platelet count are independent prognostic factors and that a combination of these factors can be used to stratify metastatic prostate cancer patients treated with endocrine therapy according to their DSS risk.

Peri-operative efficacy and long-term survival benefit of robotic-assisted radical cystectomy in septuagenarian patients compared with younger patients: a nationwide multi-institutional study in Japan.

BACKGROUND: To determine the peri-operative safety and oncological value of robotic-assisted radical cystectomy (RARC) for older and younger patients in an initial Japanese RARC series. METHODS: We retrospectively analyzed the demographics, complications, peri-operative and oncological outcomes of 253 consecutive patients with bladder cancer who underwent RARC at 34 institutions in Japan between April 2009 and March 2017. The patients were assigned to groups according to ages at surgery of < 70 (younger; n = 125) and ≥ 70 (older; n = 128) years. RESULTS: Mean Charlson comorbidity index (p = 0.045) and the incidence of a history of previous abdominal surgery (p = 0.002) were significantly higher, whereas a history of neoadjuvant chemotherapy (p = 0.028) and neobladder (p < 0.001) were significantly lower in the older group. Mean total operative time was significantly shorter (p = 0.019) and mean estimated blood loss (p = 0.013) was significantly lower in the older group. Post-operative Grade ≥ II complications were comparable at 0-30, 31-90 and 91 days after surgery despite urinary tract associations. Rates of positive surgical margins and mean numbers of removed lymph nodes were comparable between the two groups. Although 5-year overall survival rates were significantly lower (p = 0.03) for older patients, 5-year cancer-specific (p = 0.10) and recurrence-free survival rates were comparable (p = 0.20) between the groups. CONCLUSION: Using RARC potentially allows the application of less invasive procedures and cancer control for septuagenarian patients that are equivalent to those for younger patients.

Prognostic significance of the presence of tertiary Gleason grade 5 in robot-assisted radical prostatectomy specimens in Japanese patients with clinically localized prostate cancer.

BACKGROUND: The aim of this study was to study the prognostic significance of tertiary Gleason grade (TGG) 5 in patients with clinically localized prostate cancer treated with robot-assisted radical prostatectomy (RARP). METHODS: A total of 600 Japanese patients who underwent RARP for clinical stage T1-3N0M0 prostate cancer were evaluated. TGG5 was evaluated according to the International Society of Urological Pathology criterion. Cox hazard regression was used to evaluate the prognostic significance of prostate-specific antigen and pathological features in RARP specimens. RESULTS: Of the 600 RARP specimens, 92 (15%) had TGG5. TGG5 component was found in 30 (10%) of 287 cases with Gleason score (GS) 3 + 4, 55 (37%) of 149 cases with GS 4 + 3 and 7 (17%) of 40 cases with GS 4 + 4. There were no significant differences in pathological stage and surgical margin status between GS 3 + 4 with and without TGG5, as well as between GS 4 + 4 with and without TGG5. Of the 600 patients, 92 (15%) patients had biochemical recurrence (BCR) after surgery, with a median follow-up period of 42 (3-104) months. There were no differences in 5-year BCR-free survival rates between patients with GS 3 + 4 with and without TGG5 (92 vs. 100%, P = 0.16), as well as between patients with GS 4 + 3 with and without TGG5 (79 vs. 71%, P = 0.30). Similarly, there were no differences in 3-year BCRFS rates between patients with GS 4 + 4 with and without TGG5 (80 vs. 71%, P = 0.38). CONCLUSIONS: In our population, the presence of TGG5 in RARP specimens had no strong impact on pathological and prognostic outcomes.

Salvage radiation therapy for prostate cancer patients after prostatectomy.

OBJECTIVES: The aim of this study was to identify risk factors to predict a biochemical recurrence (BCR) in patients treated with salvage radiation therapy (SRT) after radical prostatectomy (RP). METHODS: We retrospectively reviewed 122 Japanese patients who received SRT for BCR after RP. Using uni- and multivariate Cox proportional hazard models, we identified the predictive factors of BCR after SRT. RESULTS: With a median follow-up of 61.3 months, 45.9% of the patients showed BCR after SRT, with 61.5 and 41.8% of non-BCR rates at the second and fifth years. Univariate proportional hazards analysis demonstrated that extraprostatic disease (P = 0.029), seminal vesicle invasion (P = 0.005), microvascular invasion (P = 0.001), postoperative Gleason score (P = 0.008) and pre-SRT prostate-specific antigen (PSA) (P = 0.005) were significantly associated with BCR after SRT. However, only the presence of microvascular invasion and a higher pre-SRT PSA were significant predictors in the multivariate analysis. The non-BCR rate in the second year after SRT for 15 patients with microvascular invasion and pre-SRT PSA > 1.2 ng/ml was only 21% compared to 72.5% of 72 patients with negative microvascular invasion and a pre-SRT PSA of <1.2 ng/ml (P = 0.000031). CONCLUSIONS: While SRT is the most important secondary treatment option for patients with BCR after RP, the effectiveness of SRT may not be uniform. The combination of risk factors such as microvascular invasion in RP specimens and pre-SRT PSA may provide a better way to stratify the risk of BCR after SRT.

Prostate-specific antigen screening impacts on biochemical recurrence in patients with clinically localized prostate cancer.

OBJECTIVE: To clarify the impact of prostate-specific antigen screening on surgical outcomes of prostate cancer. METHODS: Patients who underwent radical prostatectomy were divided into two groups according to prostate-specific antigen testing opportunity (group 1, prostate-specific antigen screening; group 2, non-prostate-specific antigen screening). Perioperative clinical characteristics were compared using the Wilcoxon rank-sum and χ2 -tests. Cox proportional hazards models were used to identify independent predictors of postoperative biochemical recurrence-free survival. RESULTS: In total, 798 patients (63.2%) and 464 patients (36.8%) were categorized into groups 1 and 2, respectively. Group 2 patients were more likely to have a higher prostate-specific antigen level and age at diagnosis and larger prostate volume. Clinical T stage, percentage of positive cores and pathological Gleason score did not differ between the groups. The 5-year biochemical recurrence-free survival rate was 83.9% for group 1 and 71.0% for group 2 (P < 0.001). On multivariate analysis, prostate-specific antigen testing opportunity (hazard ratio 2.530; P < 0.001) was an independent predictive factor for biochemical recurrence after surgery, as well as pathological T stage, pathological Gleason score, positive surgical margin and lymphovascular invasion. Additional analyses showed that prostate-specific antigen screening had a greater impact on biochemical recurrence in a younger patients, patients with a high prostate-specific antigen level, large prostate volume and D'Amico high risk, and patients meeting the exclusion criteria of the Prostate Cancer Research International Active Surveillance study. CONCLUSIONS: Detection by screening results in favorable outcomes after surgery. Prostate-specific antigen screening might contribute to reducing biochemical recurrence in patients with localized prostate cancer.

Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer.

Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo. hu11B6 demonstrates exquisite targeting specificity for KLK2. A single administration of actinium-225 labeled hu11B6 eradicates disease and significantly prolongs survival in animal models. DNA damage arising from alpha particle irradiation induces AR and subsequently KLK2, generating a unique feed-forward mechanism, which increases binding of hu11B6. Imaging data in nonhuman primates support the possibility of utilizing hu11B6 in man.

The Impact of Lateral Bladder Neck Preservation on Urinary Continence Recovery After Robot-Assisted Radical Prostatectomy.

OBJECTIVE: Urinary incontinence is one of the most bothersome adversities after robot-assisted radical prostatectomy (RARP). The aim of this study was to investigate the urinary continence recovery and the effect of various surgical techniques. MATERIALS AND METHODS: We previously reported that posterior rhabdosphincter reconstruction and nerve-sparing were independent predictors of urinary continence recovery 1 month after catheter removal in 199 patients who underwent RARP. Retrospectively, we further reviewed those 199 patients for urinary continence recovery at 3 months or later after RARP. The relationships of urinary continence with perioperative findings, including surgical procedures, were evaluated at 3 to 12 months after RARP. The Fisher exact test and Mann-Whitney rank sum test were used for evaluating variables between the groups. Multivariate logistic regression analysis was performed to investigate the association between urinary continence and perioperative factors. RESULTS: On univariate analyses, surgeon experience, lateral bladder neck preservation (BNP), anterior reconstruction, and posterior reconstruction were significantly associated with urinary continence recovery 3 months after RARP, but only lateral BNP was independently associated with urinary continence recovery in a multivariate analysis. Similarly, on univariate analyses, surgeon experience, lateral BNP, and posterior reconstruction were significantly associated with continence recovery at 6 months or later after surgery. However, multivariate analyses showed that only lateral BNP was significantly associated with urinary continence recovery 6 months or later after surgery. CONCLUSION: Although the lateral BNP technique did not affect immediate urinary continence recovery, this procedure was significantly associated with continence recovery 3 months or later after RARP.

No clinical significance of the time interval between biopsy and robotic-assisted radical prostatectomy for patients with clinically localized prostate cancer on biochemical recurrence: a propensity score matching analysis.

PURPOSE: To investigate the impact of the time interval (TI) between prostate biopsy and robot-assisted radical prostatectomy (RARP) on the risk of biochemical recurrence (BCR). METHODS: We retrospectively reviewed the medical records of 793 consecutive patients who were treated with RARP at our institution. Patients were divided into three groups, according to TI, to compare BCR-free survival (BCRFS) rates: Group 1 (n = 196), TI < 3 months; Group 2 (n = 513), 3 ≤ TI < 6 months; Group 3 (n = 84), TI ≥ 6 months. Eighty-three patients with TI ≥ 6 months were matched with an equal number of patients with TI < 6 months based on propensity scores by using four preoperative factors: prostate-specific antigen (PSA), primary (pGS) and secondary (sGS) Gleason score and positive prostate biopsy. RESULTS: The 5-year BCRFS rates for TI Groups 1, 2, and 3 were 76%, 80.7% and 82.6% (P = 0.99), respectively. The multivariate analysis revealed that PSA, pGS, sGS and a positive prostate biopsy were independent preoperative risk factors for BCR. The propensity adjusted 5-year BCRFS for patients with TI ≥ 6 months was 84.0%. This was not worse than that of patients with TI < 6 months (71.0%, P = 0.18). CONCLUSIONS: In our cohorts, a delay in the time from biopsy to RARP did not significantly affect recurrence. Therefore, hasty treatment decisions are unnecessary for at least 6 months after diagnosis of early prostate cancer.

Development of a Nomogram for Predicting Severe Neutropenia Associated With Docetaxel-Based Chemotherapy in Patients With Castration-Resistant Prostate Cancer.

BACKGROUND: Neutropenia is a major adverse event of docetaxel-based chemotherapy. The present study was undertaken to evaluate the incidence of neutropenia and to develop a nomogram for predicting Grade 4 neutropenia during the first cycle of docetaxel-based chemotherapy in patients with castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: This study included 112 patients with CRPC treated with docetaxel-based systemic chemotherapy. We evaluated the incidence and risk factors for Grade 4 neutropenia in the first cycle of chemotherapy. RESULTS: Sixty-two of 112 patients (55.4%) developed Grade 4 neutropenia in the first cycle of docetaxel-based chemotherapy. There were significant differences in age, baseline white blood cell count, and baseline neutrophil count between patients with non-Grade 4 neutropenia and those with Grade 4 neutropenia in univariate analyses. The serum prostate-specific antigen level, hemoglobin level, creatinine, albumin, Eastern Cooperative Oncology Group performance status, metastatic sites, extent of disease, and history of external beam radiotherapy to the prostate were not significantly different between the 2 groups. Multivariate logistic regression analysis showed that age (odds ratio [OR], 1.08; P = .019) and baseline neutrophil counts (OR, 0.79; P = .045) were significant independent risk factors for severe neutropenia. A nomogram and a calibration plot on the basis of these results were developed from a multivariate logistic regression analysis to predict the probability of Grade 4 neutropenia. CONCLUSION: Age and baseline neutrophil counts were significant independent risk factors for Grade 4 neutropenia. The nomogram to predict it provides useful information for the management of patients with CRPC treated with docetaxel chemotherapy.

Preoperative determinant of early postoperative renal function following radical cystectomy and intestinal urinary diversion.

PURPOSE: To identify preoperative factors correlated with postoperative early renal function in patients who had undergone radical cystectomy (RC) and intestinal urinary diversion. METHODS: We retrospectively identified 201 consecutive bladder cancer patients without distant metastasis who had undergone RC at our institution between 2003 and 2012. The estimated glomerular filtration rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology equation before RC and 3 months following RC. Univariate and stepwise multiple linear regression analyses were applied to estimate postoperative renal function and to identify significant preoperative predictors of postoperative renal function. RESULTS: Patients who had undergone intestinal urinary diversion and were available for the collection of follow-up data (n = 164) were eligible for the present study. Median preoperative and postoperative eGFRs were 69.7 (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In univariate analyses, age, preoperative proteinuria, thickness of abdominal subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative eGFR, and urinary diversion type were significantly associated with postoperative eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age, and TSF were significant factors for predicting postoperative eGFR (p < 0.001, p = 0.02, and p = 0.046, respectively). The estimated postoperative eGFRs correlated well with the actual postoperative eGFRs (r = 0.65, p < 0.001). CONCLUSIONS: Preoperative eGFR, age, and TSF were independent preoperative factors for determining postoperative renal function in patients who had undergone RC and intestinal urinary diversion. These results may be used for patient counseling before surgery, including the planning of perioperative chemotherapy administration.

Clinical significance of preoperative renal function and gross hematuria for intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To investigate the predictive values of perioperative factors and to develop a nomogram for intravesical recurrence after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. METHODS: A retrospective analysis of 144 patients who underwent radical nephroureterectomy from 1996 to 2014 was carried out. The actuarial probabilities of the intravesical recurrence-free survival rate were calculated using the Kaplan-Meier method. Prognostic indicators for intravesical recurrence were identified using competing-risks regression analyses. RESULTS: Intravesical recurrence occurred in 63 patients during the follow-up period. The intravesical recurrence-free survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In univariate analysis, the presence of gross hematuria (P = 0.028) and the preoperative serum creatinine level (P = 0.033) were significantly associated with intravesical recurrence. In multivariate analysis, the presence of gross hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145-3.496; P = 0.013) and the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95% CI 1.161-3.534; P = 0.021) were independent predictors for intravesical recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the model was developed. The concordance index of this model was 0.632. CONCLUSION: The presence of gross hematuria and preoperative serum creatinine levels seem to be independent predictors for intravesical recurrence after radical nephroureterectomy. Our nomogram developed based on these factors might aid in appropriate patient selection for clinical trials of novel therapeutic interventions, including administration of intravesical chemotherapy.

A Case of Primary Small-Cell Carcinoma of the Bladder.

Primary small-cell carcinoma arising from the bladder (SmCCB) is uncommon. It differs from urothelial carcinoma (UC), the most common type of bladder cancer, with respect to its cell of origin, biology, and prognosis. Biologically, prostatic SmCCB is much more aggressive than UC, and the prognosis for cases with distant metastasis is especially poor. We report here a case of primary SmCCB (cT3bN1M0) treated with radical cystectomy.

Sarcopenia as a Novel Preoperative Prognostic Predictor for Survival in Patients with Bladder Cancer Undergoing Radical Cystectomy.

PURPOSE: To investigate the prognostic significance of sarcopenia on long-term outcomes in patients with bladder cancer after radical cystectomy (RC). METHODS: We retrospectively reviewed 136 patients undergoing RC for urothelial carcinoma at our institution. Prognostic impact of the preoperative clinical, laboratory, and radiologic parameters were evaluated by Cox proportional hazard model analyses, and a nomogram was developed to predict cancer-specific survival (CSS) after RC. RESULTS: The mean follow-up was 46.7 months. Patients with sarcopenia had a significantly shorter CSS than those without sarcopenia. On univariate Cox analysis, clinical T stage, histology of transurethral resection of bladder tumor (TURBT) specimen, pretreatment hemoglobin, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment serum C-reactive protein level, pretreatment serum albumin level, presence of hydronephrosis, and presence of sarcopenia were associated with significantly worse CSS. On multivariate Cox stepwise analysis, sarcopenia (hazard rate [HR] = 2.3, p = 0.015), clinical T stage (cT4: HR = 5.3; p = 0.0096), presence of hydronephrosis (HR = 2.0; p = 0.033), histology of TURBT specimen (HR = 2.2, p = 0.044), and NLR (HR = 1.3; p = 0.0048) were significant independent predictors of an unfavorable prognosis Based on the results of the multivariate analysis, we developed a nomogram to predict 1-, 3-, and 5-year CSS after RC. CONCLUSIONS: Sarcopenia, clinical T stage, presence of hydronephrosis, histology of TURBT specimen, and NLR are novel preoperative prognostic factors even after adjustment for other known preoperative predictors in patients undergoing RC for bladder cancer.

Assessment of Prostate Cancer Aggressiveness by Use of the Combination of Quantitative DWI and Dynamic Contrast-Enhanced MRI.

OBJECTIVE: The objective of this study was to investigate whether the apparent diffusion coefficient (ADC) value from DWI and the forward volume transfer constant (K(trans)) value from dynamic contrast-enhanced MRI independently predict prostate cancer aggressiveness, and to determine whether the combination of both parameters performs better than either parameter alone in assessing tumor aggressiveness before treatment. MATERIALS AND METHODS: This retrospective study included 158 men with histopathologically confirmed prostate cancer who underwent 3-T MRI before undergoing prostatectomy in 2011. Whole-mount step-section pathologic maps identified 195 prostate cancer foci that were 0.5 mL or larger; these foci were then volumetrically assessed to calculate the per-tumor ADC and K(trans) values. Associations between MRI and histopathologic parameters were assessed using Spearman correlation coefficients, univariate and multivariable logistic regression, and AUCs. RESULTS: The median ADC and K(trans) values showed moderate correlation only for tumors for which the Gleason score (GS) was 4 + 4 or higher (ρ = 0.547; p = 0.042). The tumor ADC value was statistically significantly associated with all dichotomized GSs (p < 0.005), including a GS of 3 + 3 versus a GS of 3 + 4 or higher (AUC, 0.693; p = 0.001). The tumor K(trans) value differed statistically significantly only between tumors with a GS of 3 + 3 and those with a primary Gleason grade of 4 (p ≤ 0.015), and it made a statistically significant contribution only in differentiating tumors with a GS of 4 + 3 or higher (AUC, 0.711; p < 0.001) and those with a GS of 4 + 4 or higher (AUC, 0.788; p < 0.001) from lower-grade tumors. Combining ADC and K(trans) values improved diagnostic performance in characterizing tumors with a GS of 4 + 3 or higher and those with a GS of 4 + 4 or higher (AUC, 0.739 and 0.856, respectively; p < 0.01). CONCLUSION: Although the ADC value helped to differentiate between all GSs, the K(trans) value was only a benefit in characterizing more aggressive tumors. Combining these parameters improves their performance in identifying patients with aggressive tumors who may require radical treatment.

Impact of a preoperatively estimated prostate volume using transrectal ultrasonography on surgical and oncological outcomes in a single surgeon's experience with robot-assisted radical prostatectomy.

BACKGROUND: To assess the impact of preoperatively estimated prostate volume (PV) using transrectal ultrasonography (TRUS) on surgical and oncological outcomes in robot-assisted radical prostatectomy (RARP). METHODS: We analyzed the experience of a single surgeon at our hospital who performed 436 RARPs without neoadjuvant hormone therapy between August 2006 and December 2013. Patients were divided into three groups according to their preoperative PV calculated using TRUS (PV ≤ 20 cm(3): group 1, n = 61; 20 < PV < 50 cm(3): group 2, n = 303; PV ≥ 50 cm(3): group 3, n = 72). RESULTS: Blood loss was significantly higher in group 3 than in group 1 and group 2. In stage pT2 patients, the rate of positive surgical margin (PSM) was significantly lower in group 3 than in group 1. In addition, perioperative complications significantly increased with increasing PV, while the extraprostatic extension (EPE) rate significantly decreased with increasing PV. The preoperative biopsy Gleason score, prostate-specific antigen (PSA) density, and clinical T2 stage were inversely correlated with increasing PV. Biochemical recurrence-free survival after RARP was significantly lower in group 1 than in groups 2 and 3. CONCLUSIONS: A large prostate size was significantly associated with increased blood loss and a higher rate of perioperative complications. A small prostate size was associated with a higher PSM rate, PSA density, Gleason score, EPE rate, and biochemical recurrence rate. These results suggest that RARP was technically challenging in patients with large prostates, whereas small prostates were associated with unfavorable oncological outcomes.

Automatic classification of prostate cancer Gleason scores from multiparametric magnetic resonance images.

Noninvasive, radiological image-based detection and stratification of Gleason patterns can impact clinical outcomes, treatment selection, and the determination of disease status at diagnosis without subjecting patients to surgical biopsies. We present machine learning-based automatic classification of prostate cancer aggressiveness by combining apparent diffusion coefficient (ADC) and T2-weighted (T2-w) MRI-based texture features. Our approach achieved reasonably accurate classification of Gleason scores (GS) 6(3 + 3) vs. ≥7 and 7(3 + 4) vs. 7(4 + 3) despite the presence of highly unbalanced samples by using two different sample augmentation techniques followed by feature selection-based classification. Our method distinguished between GS 6(3 + 3) and ≥7 cancers with 93% accuracy for cancers occurring in both peripheral (PZ) and transition (TZ) zones and 92% for cancers occurring in the PZ alone. Our approach distinguished the GS 7(3 + 4) from GS 7(4 + 3) with 92% accuracy for cancers occurring in both the PZ and TZ and with 93% for cancers occurring in the PZ alone. In comparison, a classifier using only the ADC mean achieved a top accuracy of 58% for distinguishing GS 6(3 + 3) vs. GS ≥7 for cancers occurring in PZ and TZ and 63% for cancers occurring in PZ alone. The same classifier achieved an accuracy of 59% for distinguishing GS 7(3 + 4) from GS 7(4 + 3) occurring in the PZ and TZ and 60% for cancers occurring in PZ alone. Separate analysis of the cancers occurring in TZ alone was not performed owing to the limited number of samples. Our results suggest that texture features derived from ADC and T2-w MRI together with sample augmentation can help to obtain reasonably accurate classification of Gleason patterns.

Prediction of renal function after nephroureterectomy in patients with upper tract urothelial carcinoma.

OBJECTIVE: The estimated glomerular filtration rate is significantly decreased after nephroureterectomy. Deteriorating renal function likely affects the eligibility for cisplatin-based chemotherapy in patients with upper tract urothelial carcinoma. The present study was undertaken to identify preoperative factors for the prediction of postoperative renal function and develop a prediction model. METHODS: Between June 1996 and January 2014, 110 patients who underwent radical nephroureterectomy at our institution were analyzed in this study. The estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease study equation. Univariate linear regression analyses were performed to investigate the correlation between postoperative estimated glomerular filtration rate and preoperative variables. A stepwise multivariate linear regression analysis was performed to identify independent predictors of postoperative estimated glomerular filtration rate. RESULTS: Comparison of preoperative and postoperative estimated glomerular filtration rate for each patient showed a median difference of 13.1 ml/min/1.73 m(2). The postoperative estimated glomerular filtration rate was significantly lower than the preoperative estimated glomerular filtration rate (P < 0.001). On univariate analysis, age and preoperative estimated glomerular filtration rate were significantly correlated with postoperative estimated glomerular filtration rate. On multivariate analysis, age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictive factors of postoperative estimated glomerular filtration rate. The predicted postoperative estimated glomerular filtration rate, which was calculated using these independent factors, showed a significant correlation with the observed postoperative estimated glomerular filtration rate (correlation coefficient = 0.7533). CONCLUSIONS: Age, preoperative estimated glomerular filtration rate and the presence of hydronephrosis were independent predictors of postoperative estimated glomerular filtration rate in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. The predicted postoperative estimated glomerular filtration rate based on these factors may be useful for choosing alternative management strategies such as neoadjuvant chemotherapy for patients with upper tract urothelial carcinoma.

The role of single instillation chemotherapy in patients who receive subsequent bacillus Calmette-Guérin: A retrospective single centre study, and systematic review of the literature.

INTRODUCTION: This retrospective study was undertaken to evaluate the combined effect of immediate intravesical chemotherapy and subsequent bacillus Calmette-Guérin (BCG) therapy. METHODS: The study population consisted of 207 intermediate- or high-risk patients with non-muscle invasive bladder cancer who underwent an induction course of BCG between 1993 and 2007. We introduced single immediate instillation of 50 mg epirubicin for all cases in 2004, and thus earlier cases could be considered as historical controls. The primary endpoint was recurrence-free survival (RFS). For cumulative analysis, we systematically reviewed studies indexed in databases. Including ours, the records of 856 patients from a total of 7 studies, including ours, were finally analyzed. RESULTS: In our cohort, the 5-year RFS in patients who received the combination therapy was 66.2%, compared to 55.2% in the BCG alone group (p = 0.149). Multivariate analysis on tumour recurrence showed that patients with the combination therapy had a hazard ratio (HR) of 0.74 (p = 0.189). A subsequent literature review revealed that RFS rates in the combination groups were higher than those in the corresponding BCG alone groups in 4/7 studies (p = 0.02-0.15), and lower in 1 study (p = 0.51). We identified 5 studies which examined a HR for combination therapy, and performed a cumulative analysis. Adding a single chemo-instillation prior to BCG resulted in a significant reduction in tumour recurrence (summary HR 0.69, p = 0.010). CONCLUSIONS: Our analysis suggested that the combination of single chemo-instillation with subsequent BCG therapy exhibited an additive effect against potential tumour recurrence.