In radical prostatectomy (RP) procedures, sparing the neurovascular bundles adjacent to the posterolateral aspect of the prostatic fascia has often been suggested as a possible risk factor for positive surgical margins. Here we aimed to quantify the probability of extracapsular extension (ECE) at the posterolateral side of the prostate to aid in nerve-sparing decision making.
Materials and Methods
We evaluated 472 patients who underwent RP between July 2007 and January 2012. All patients underwent preoperative magnetic resonance imaging (MRI) with diffusion-weighted imaging and apparent diffusion coefficient mapping. We analyzed 944 side-specific prostate lobes with preoperative variables. To quantify the risk of side-specific posterolateral ECE after RP, we developed a risk-stratification scoring system through logistic regression analysis.
Overall, 20.6% of 944 prostate lobes had ECE. In the multivariate analysis, prostate-specific antigen (PSA), biopsy Gleason score ≥7, percentage of side-specific cores with tumor, and posterolateral ECE on MRI were independent predictive factors of posterolateral ECE. On internal and external validation to calculate the predicted risk, the Hosmer-Lemeshow goodness-of-fit test showed good calibration (p=0.396).
PSA, biopsy Gleason score, percentage of side-specific cores with tumor, and posterolateral ECE on MRI are independent predictors of posterolateral ECE. The scoring system derived from this study will provide objective parameters for use when deciding if the neurovascular bundle can be safely spared.
Magnetic resonance imaging; Prostatectomy; Prostatic neoplasms
To assess the clinical efficacy and toxicity of whole pelvic intensity-modulated radiotherapy (WP-IMRT) for high-risk prostate cancer.
Materials and Methods
Patients with high-risk prostate cancer treated between 2008 and 2013 were reviewed. The study included patients who had undergone WP-IMRT with image guidance using electronic portal imaging devices and/or cone-beam computed tomography. The endorectal balloon was used in 93% of patients. Patients received either 46 Gy to the whole pelvis plus a boost of up to 76 Gy to the prostate in 2 Gy daily fractions, or 44 Gy to the whole pelvis plus a boost of up to 72.6 Gy to the prostate in 2.2 Gy fractions.
The study cohort included 70 patients, of whom 55 (78%) had a Gleason score of 8 to 10 and 50 (71%) had a prostate-specific antigen level > 20 ng/mL. The androgen deprivation therapy was combined in 62 patients. The biochemical failure-free survival rate was 86.7% at 2 years. Acute any grade gastrointestinal (GI) and genitourinary (GU) toxicity rates were 47% and 73%, respectively. The actuarial rate of late grade 2 or worse toxicity at 2 years was 12.9% for GI, and 5.7% for GU with no late grade 4 toxicity.
WP-IMRT was well tolerated with no severe acute or late toxicities, resulting in at least similar biochemical control to that of the historic control group with a small field. The long-term efficacy and toxicity will be assessed in the future, and a prospective randomized trial is needed to verify these findings.
Prostate neoplasms; Intensity-modulated radiotherapy; Complications
There are concerns whether megestrol acetate (MA) stimulates the growth of prostate cancer in castration-resistant prostate cancer (CRPC). We evaluated the effect of cumulative doses of MA on the disease-specific survival (DSS) in patients with CRPC who were receiving Docetaxel-based chemotherapy. From July 2003 through June 2009, we identified 109 consecutive patients with CRPC and who had received docetaxel-based chemotherapy. Of these patients, 68 (62.4%) have not received MA, whereas 21 patients (19.3%) and 20 patients (18.3%) had received low dose MA (total ≤ 18,400 mg) and high dose MA (total > 18,400 mg), respectively. We assessed the effect of several variables on DSS. None of the clinicopathological variables differed among the three groups. When comparing DSS using Kaplan-Meier analysis, there was no statistically significant survival differences among the three groups (P = 0.546). Using multivariate Cox proportional analyses with backward elimination, the number of docetaxel cycles was only significant factor predicting DSS (HR: 0.578, 95% CI: 0.318-0.923, P = 0.016). Cumulative doses of MA as adjuvant treatment for patients with CRPC and who are receiving docetaxel-based chemotherapy, did not affect their DSS. Therefore, MA can be safely administered in cachexic patients with CRPC.
Cachexia; Castration-Resistant Prostate Cancer; Docetaxel; Megestrol Acetate; Survival
To develop a nomogram using transrectal ultrasound (TRUS)-derived information for predicting high grade (HG) prostate cancer (PCa) on initial biopsy.
Data were collected on 1,048 men with serum prostate-specific antigen (PSA) levels 4.0 to 9.9 ng/mL who underwent an initial prostate biopsy. Two logistic regression-based nomograms were constructed to predict the detection of PCa. Nomogram-1 incorporated age, digital rectal examination, PSA and percent free PSA data, whereas nomogram-2 incorporated those factors plus TRUS-derived information (i.e., prostate volume and the presence of hypoechoic lesions). The prediction of any PCa and HGPCa (Gleason score≥7) were determined. Twenty percent of the data were randomly reserved for study validation, and the predictive accuracies of the two nomograms were directly compared.
Of the 1,048 men who underwent biopsy, 216 (20.6%) were found to have any PCa, and 97 (9.3%) were found to have HGPCa. All six risk factors were found to be independent predictors for both any PCa and HGPCa. The area under curve (AUC) for nomogram-2 was 0.76 (95% confidence interval [CI], 0.72 to 0.81) for predicting any PCa, and 0.83 (95% CI, 0.79 to 0.88) for predicting HGPCa. These AUCs were greater than those for nomogram-1 (0.72 [95% CI, 0.68 to 0.76 for any PCa; P<0.001], 0.78 [95% CI, 0.72 to 0.83 for HGPCa; P<0.001]). Removing the TRUS-derived information from nomogram-2 resulted in an incremental AUC decrease of 0.052 for any PCa and 0.063 for HGPCa.
The nomogram using TRUS-derived information had a high predictive accuracy for HGPCa on initial prostate biopsy.
Prostatic neoplasms; Biopsy; Nomograms; Ultrasonography
Prostate-specific antigen (PSA) response rate (>50% PSA decline in pretreatment PSA following chemotherapy) carries a significant survival advantage in castration-resistant prostate cancer (CRPC). We compared PSA response rates in first-, second- and third-line chemotherapy after failure of previous chemotherapy according to chemotherapeutic agents.
We retrospectively evaluated the oncological outcomes and PSA response rates of 384 patients with CRPC, who were treated with chemotherapy and had histologically proven adenocarcinoma of the prostate with failure after androgen ablation therapy between 1991 and 2012, at Asan Medical Center.
In 384 eligible patients, the median age was 67.5 years. The median pretreatment PSA and initial Gleason scores at baseline were 92.4 ng/mL (range, 2.0 to 6,370 ng/mL) and 9 (range, 6 to 10), respectively. The time from first diagnosis of prostate cancer to CRPC was 23 months (range, 1 to 164 months). As first-line chemotherapy, 245 patients (63.8%) received estramustine, 91 (23.7%) received docetaxel, and 39 (10.2%) received mitoxantrone. The PSA response rates were 39.6%, 51.6%, and 46.2%, respectively. Of 169 patients with second-line chemotherapy, estramustine was 15 (8.9%), docetaxel was 84 (49.7%), and mitoxantrone was 52 (30.8%). PSA response rates were 57.1%, 52%, and 28.0%, respectively. Of 81 patients with third-line chemotherapy, estramustine was 18 (22.2%), docetaxel was 16 (19.8%), and mitoxantrone was 28 (34.6%). The PSA response rates were 41.2%, 53.8%, and 11.1%, respectively. Declines in serum PSA levels of at least 50% occurred more frequently after treatment with docetaxel than with other chemo-agents regardless of second-and third-line chemotherapy. Even in third-line chemothrapy, docetaxel maintained the PSA response rate, whereas the PSA response rate of other agents, including mitoxantrone, decreased in patients in whom prior therapy failed.
Docetacel was the most effective chemotherapeutic agent in second- and third-line trials of chemotherapy in Korean CRPC patients. Although docetaxel is not used as first-line chemotherapy, and new agents are not available for therapy in CRPC patients, we can consider docetaxel a second- or third-line chemotherapy in CRPC.
Castration refractory prostate cancer; Chemotherapy; Prostate-specific antigen
To investigate whether tumor aggressiveness in patients with prostate cancer has changed in Korea since the introduction of prostate-specific antigen (PSA) testing.
Materials and Methods
The data from 2,508 patients with pathologically confirmed prostate cancer who underwent radical prostatectomy at Asan Medical Center between 2000 and 2011 were reviewed. The patients were divided into four 3-year time series, and the changes between the groups in terms of serum PSA levels, pathological Gleason score (GS), and pathological stage were assessed. The change in GS over time in organ-confined disease and in patients whose PSA was below 10 ng/ml was also analyzed.
The mean PSA levels dropped significantly over the 12-year period (p<0.001). The frequency of organ-confined disease increased (55.7% vs. 64.7% vs. 62.9% vs. 63.5%, p=0.043). The frequency of patients with a GS of 8 or more decreased (38.9% vs. 25.7% vs. 18.2% vs. 19.7%) and the frequency of patients with a GS of 6 or less increased (15.0% vs. 18.9% vs. 26.7% vs. 18.2%, p=0.003). However, the vast majority (more than 70%) of all cases had a high GS (7 or greater) at all time points. The GS distribution did not change over time in patients whose PSA levels were below 10 ng/ml or in those who had organ-confined disease.
In 2000 to 2011, the preoperative PSA, pathological stage, and pathological GS dropped. However, the majority of the prostate cancers in Korean men were poorly differentiated, even when the patients had organ-confined disease or their PSA levels were less than 10 ng/ml.
Korea; Neoplasm grading; Prostatic neoplasms
The aim of this study was to evaluate the recent changes in the clinicopathologic features of prostate cancer in Korea and to compare these features with those of Western populations.
Materials and Methods
We retrospectively reviewed the data of 1582 men undergoing radical prostatectomy for clinically localized prostate cancer between 1995 and 2007 at 10 institutions in Korea for comparison with Western studies. The patients were divided into two groups in order to evaluate the recent clinicopathological changes in prostate cancer: Group 1 had surgery between 1995 and 2003 (n=280) and Group 2 had surgery between 2004 and 2007 (n=1302). The mean follow-up period was 24 months.
Group 1 had a higher prostate-specific antigen level than Group 2 (10.0 ng/mL vs. 7.5 ng/mL, respectively; p<0.001) and a lower proportion of biopsy Gleason scores ≤6 (35.0% vs. 48.1%, respectively; p<0.001). The proportion of patients with clinical T1 stage was higher in Group 2 than in Group 1. Group 1 had a lower proportion of organ-confined disease (59.6% vs. 68.6%; p<0.001) and a lower proportion of Gleason scores ≤6 (21.3% vs. 33.0%; p<0.001), compared to Group 2. However, the relatively higher proportion of pathologic Gleason scores ≤6 in Group 2 was still lower than those of Western men, even though the proportion of organ-confined disease reached to that of Western series.
Korean men with prostate cancer currently present better clinicopathologic parameters. However, in comparison, Korean men still show relatively worse pathologic Gleason scores than Western men.
Prostate neoplasms; prostatectomy; treatment outcome; ethnic groups
To evaluate the treatment outcome and prognostic factor after postoperative radiotherapy in retroperitoneal sarcoma.
Materials and Methods
Forty patients were treated with surgical resection and postoperative radiotherapy for retroperitoneal sarcoma from August 1990 to August 2008. Treatment volume was judged by the location of initial tumor and surgical field, and 45-50 Gy of radiation was basically delivered and additional dose was considered to the high-risk area.
The median follow-up period was 41.4 months (range, 3.9 to 140.6 months). The 5-year overall survival (OS) was 51.8% and disease free survival was 31.5%. The 5-year locoregional recurrence free survival was 61.9% and distant metastasis free survival was 50.6%. In univariate analysis, histologic type (p = 0.006) was the strongest prognostic factor for the OS and histologic grade (p = 0.044) or resection margin (p = 0.032) had also effect on the OS. Histologic type (p = 0.004) was unique significant prognostic factor for the actuarial local control.
Retroperitoneal sarcoma still remains as a poor prognostic disease despite the combined modality treatment including surgery and postoperative radiotherapy. Selective dose-escalation of radiotherapy or combination of effective chemotherapeutic agent must be considered to improve the treatment result especially for the histopathologic type showing poor prognosis.
Sarcoma; Retroperitoneal; Radiotherapy; Postoperative; Outcome
The survival benefits of adjuvant androgen-deprivation therapy (ADT) in prostate cancer and lymph node metastasis remain unclear. We assessed the role of ADT in disease progression after radical prostatectomy (RP).
Materials and Methods
Of 937 patients who underwent RP, we identified 40 (4.2%) who had lymph node metastasis. A total of 18 received adjuvant ADT (ADT group) and 22 were observed (observation group). Clinical progression-free survival (PFS), cancer- specific survival (CSS), and overall survival (OS) were compared in the 2 groups. Prognostic factors for clinical progression and biochemical recurrence (BCR) were analyzed.
The 5-year PFS, CSS, and OS of the entire cohort were 75.0%, 85.0%, and 72.5%, respectively. In the ADT group, 6 patients (33.3%) showed clinical progression at a median 42.7 months. The 5-year PFS, CSS, and OS rates of this group were 72.2%, 83.3%, and 72.2%, respectively. In the observation group, 14 patients (63.6%) received salvage therapy owing to BCR. Nine patients (40.9%) with BCR in the observation group showed clinical progression at a median 43.4 months after RP. The 5-year PFS, CSS, and OS rates of this group were 77.2%, 86.4%, and 72.8%, respectively. In the observation group, the BCR rate was lower in patients with pT3a or less disease than in those with pT3b disease.
Adjuvant ADT in node-positive prostate cancer did not reduce or delay disease progression or improve survival. Because a substantial number of untreated patients with pT3a or less disease did not experience recurrence, administration of ADT should be initiated carefully. However, in patients with pT3b disease, adjuvant ADT and radiotherapy could be considered.
Androgens; Lymph nodes; Prostatectomy
To assess the validity of the 2009 TNM classification for renal cell carcinoma (RCC) and compare its ability to predict survival relative to the 2002 classification.
Materials and Methods
We identified 1,691 patients who underwent radical nephrectomy or partial nephrectomy for unilateral, sporadic RCC between 1989 and 2007. Cancer-specific survival was estimated by the Kaplan-Meier method and was compared among groups by the log-rank test. Associations of the 2002 and 2009 TNM classifications with death from RCC were evaluated by Cox proportional hazards regression models. The predictive abilities of the two classifications were compared by using Harrell's concordance (c) index.
There were 234 deaths from RCC a mean of 38 months after nephrectomy. According to the 2002 primary tumor classification, 5-year cancer-specific survival was 97.6% in T1a, 92.0% in T1b, 83.3% in T2, 61.9% in T3a, 51.1% in T3b, 40.0% in T3c, and 33.6% in T4 (p for trend<0.001). According to the 2009 classification, 5-year cancer-specific survival was 83.2% in T2a, 83.8% in T2b, 62.6% in T3a, 41.1% in T3b, 50.0% in T3c, and 26.1% in T4 (p for trend<0.001). The c index for the 2002 primary tumor classification was 0.810 in the univariate analysis and increased to 0.906 in the multivariate analysis. The c index for the 2009 primary tumor classification was 0.808 in the univariate analysis and increased to 0.904 in the multivariate analysis.
Our data suggest that the predictive ability the 2009 TNM classification is not superior to that of the 2002 classification.
Kidney neoplasms; Mortality; Neoplasm staging; Prognosis; Renal cell carcinoma
We compared the efficacy of radical cystectomy (RC) and non-RC treatment [transurethral resection of bladder tumor (TURB) only, partial cystectomy, or TURB followed by radiotherapy] in octogenarians with muscle-invasive bladder cancer (MIBC).
Materials and Methods
A total of 177 patients aged 80 years or more underwent TURB at our institute, and 41 patients had MIBC according to the histologic examination. Fourteen patients with lymph node or distant metastasis were excluded, and 27 patients were ultimately included. Patients were stratified by treatment modality (RC vs. non-RC), Charlson Comorbidity Index (low CCI vs. high CCI), and clinical tumor stage (organ-confined disease vs. extravesical disease). The effects of several variables on cancer-specific and overall survival were assessed.
Of the 27 patients, 11 (41%) underwent RC and 16 (59%) underwent non-RC treatment. Patients in the RC group were younger and more likely to have low CCI scores. There were no significant differences in overall or cancer-specific survival in the RC and non-RC groups. Patients with clinically organ-confined disease had better survival outcomes than did those with extravesical disease. Stratification of patients by CCI indicated that overall survival was better in patients with low CCI scores (p=0.013), although cancer-specific survival was similar in the two CCI groups. Univariate and multivariate analysis indicated that clinical tumor stage and CCI were independently associated with overall survival.
RC in octogenarians with MIBC does not improve overall survival compared with other treatment modalities. However, clinically organ-confined disease and low CCI score were associated with better overall survival.
Aged; Comorbidity; Cystectomy; Urinary bladder neoplasms
We investigated the clinical significance of large difference (≥ 2 points) between biopsy-derived (bGS) and post-prostatectomy Gleason scores (pGS). At 14 medical centers in Korea, 1,582 men who underwent radical prostatectomy for prostate cancer were included. According to the difference between bGS and pGS, the patients were divided into three groups: A (decreased in pGS ≥ 2, n = 30), B (changed in pGS ≤ 1, n = 1,361; control group), and C (increased in pGS ≥ 2, n = 55). We evaluated various clinicopathological factors of prostate cancer and hazards for biochemical failure. Group A showed significantly higher mean maximal percentage of cancer in the positive cores (max%) and pathological T stage than control. In group C, the number of biopsy core was significantly smaller, however, tumor volume and max% were significantly higher and more positive biopsy cores were presented than control. Worse pathological stage and more margin-positive were observed in group A and C than in control. Hazard ratio for biochemical failure was also higher in group A and C (P = 0.001). However, the groups were not independent factors in multivariate analysis. In conclusion, large difference between bGS and pGS shows poor prognosis even in the decreased group. However it is not an independent prognostic factor for biochemical failure.
Prostatic Neoplasms; Gleason Score; Prognosis
Over the past decade, continent urinary diversion, especially orthotopic bladder substitutions, has become increasingly popular following radical cystectomy for bladder cancer. The ultimate goal of orthotopic bladder substitution is to offer patients the best quality of life, similar to that of patients with native bladders. To achieve that purpose, surgeons should be familiar with the characteristics of good candidates for neobladders, the possible intraoperative and postoperative problems related to the surgery, and the solutions to these problems. Postoperative surveillance and instructions given to the patients also contribute to successful, functional results. Here, we reviewed the indications, pitfalls, and solutions for orthotopic bladder substitutions and the patients' quality of life after surgery. When performed properly, orthotopic continent diversion offers good quality of life with few long-term complications. Therefore, we believe it is the best option for the majority of patients requiring cystectomy.
Cystectomy; Quality of life; Urinary bladder; Urinary bladder neoplasms; Urinary diversion
The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma.
Materials and Methods
We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery.
Malignant tumors were significantly larger than benign tumors (11.1±4.0 cm vs. 6.2±3.4 cm, p<0.001), and postoperative persistence of arterial hypertension was more frequent after removal of malignant than benign tumors (p=0.001). Among the 147 patients without metastatic disease at diagnosis, those who developed metastasis had significantly lower concentrations of urinary catecholamine metabolites per unit of tumor, including vanillylmandelic acid (1.2 vs. 3.7 mg/day/cm, p=0.049), epinephrine (4.5 vs. 168.9 µg/day/cm, p=0.008), and norepinephrine (13.1 vs. 121.8 mg/day/cm, p<0.001). The overall 5-year metastasis-free survival rate was 84.4% and was significantly higher in patients with smaller tumors (≤5.5 vs. >5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (>2.1 vs. ≤2.1 mg/day/cm; 94.9% vs. 70.9%, p=0.019).
Large tumor size (>5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (≤2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.
Adrenal gland neoplasms; Catecholamines; Pheochromocytoma; Tumor burden
Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC.
Materials and Methods
The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort.
Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827.
Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are considered.
Prostatic neoplasms; nomograms; insignificant
To analyze the biochemical recurrence-free and cancer-specific survival after radical prostatectomy in a consecutive series of patients with prostate cancer.
Materials and Methods
We retrospectively reviewed data for 1,822 patients who underwent radical prostatectomy with pelvic lymph node dissection at our institution between 1990 and 2009. After excluding 498 patients who were treated with neoadjuvant androgen deprivation therapy or who were followed up for ≤6 months, we included 1324 patients (mean age, 64.4 years; mean prostate-specific antigen [PSA] level, 12.3 ng/ml). We assessed patient age at the time of surgery, preoperative PSA concentration, biopsy and pathologic Gleason scores, pathologic stage, surgical margin status, disease progression, and survival.
The mean follow-up time was 40 months (range, 6-193 months). The 5- and 10-year biochemical recurrence-free survival rates were 73.2% and 66.2%, respectively, and the 10-year cancer-specific survival rate was 92.4%. The mean time from surgery to biochemical recurrence was 18 months. In the multivariate analysis, Gleason score (4+3 vs. 2-6, p=0.004; 8-10 vs. 2-6, p<0.001), pathologic stage (pT3a vs. pT2, p=0.001; pT3b-4 vs. pT2, p<0.001; pN1 vs. pT2, p<0.001), and resection margin status (p<0.001) were statistically significant predictors of biochemical recurrence, with only pathologic stage (pT3b-4 vs. pT2, p=0.006; pN1 vs. pT2, p=0.010) being a statistically significant predictor of cancer-specific survival.
Radical prostatectomy resulted in favorable cancer control in more than 70% of patients after 5 years and a low (<10%) cancer-specific mortality rate after 10 years. The factors predictive of biochemical recurrence were Gleason score, pathologic stage, and resection margin status.
Prostatectomy; Prostatic neoplasms
We developed a nomogram to predict the probability of extracapsular extension (ECE) in localized prostate cancer and to determine when the neurovascular bundle (NVB) may be spared. Total 1,471 Korean men who underwent radical prostatectomy for prostate cancer between 1995 and 2008 were included. We drew nonrandom samples of 1,031 for nomogram development, leaving 440 samples for nomogram validation. With multivariate logistic regression analyses, we made a nomogram to predicts the ECE probability at radical prostatectomy. Receiver operating characteristic (ROC) analyses were also performed to assess the predictive value of each variable alone and in combination. The internal validation was performed from 200 bootstrap re-samples and the external validation was also performed from the another cohort. Overall, 314 patients (30.5%) had ECE. Age, Prostate specific antigen (PSA), biopsy Gleason score, positive core ratio, and maximum percentage of biopsy tumor were independent predictors of the presence of ECE (all P values <0.05). The nomogram predicted ECE with good discrimination (an area under the ROC curve of 0.777). Our nomogram allows for the preoperative identification of patients with an ECE and may prove useful in selecting patients to receive nerve sparing radical prostatectomy.
Nomograms; Patient Selection; Prostatic neoplasms; Prostatectomy
Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil®) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-α. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-α (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-α (T), TNF-α and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.
Dendritic Cells; Prostatic Neoplasms; Cancer Vaccines; Immunotherapy
To analyze the preoperative clinical and pathological characteristics of patients with pT0 prostate cancer.
Materials and Methods
We retrospectively reviewed the records of 702 patients who underwent radical prostatectomy (RP) at our institution between January 2004 and July 2008 for clinically localized prostate cancer. If there was no evidence of residual tumor in the pathological specimen of the prostate, a patient was staged as pT0. Patients with pT0 disease were compared with a control group of patients who were operated on during the same period.
Overall, 9 (1.3%) patients were staged as pT0 on the pathologic examination. Significant differences were observed between the pT0 group and the control patients in the biopsy Gleason score (p=0.004), the number of positive cores on biopsy (p=0.018), the tumor length of positive cores (p<0.001), and prostate volume (p=0.015). Cutoff values predictive of pT0 tumor status were defined as a biopsy Gleason score sum ≤6, 2 or fewer positive biopsy cores, tumor length on biopsy ≤2 mm, and prostate volume >30 cm3. Whereas 8 of the 9 (88.9%) pT0 patients showed all of these characteristics, only 55 of the 693 (7.9%) control patients fulfilled the criteria. The combination suggested above afforded a sensitivity of 88.8% and a specificity of 92.1% for the prediction of pT0 status.
The frequency of pT0 prostate cancer seen on RP was 1.3%. A combination of clinicopathological features, incorporating a biopsy Gleason score, the number of positive biopsy cores, tumor length on biopsy, and prostate volume, was useful to predict pT0 stage on RP.
Biopsy; Neoplasm staging; Prostatectomy; Prostatic neoplasms
To assess the efficacy and safety of treating Korean patients with metastatic hormone-refractory prostate cancer (HRPC) using docetaxel plus prednisolone chemotherapy.
Materials and Methods
This was a retrospective cohort study performed in 98 patients with metastatic HRPC between October 2003 and April 2008. After screening, 72 patients fit the eligibility criteria for inclusion in this study. Treatment consisted of 5 mg prednisolone twice daily and 75 mg/m2 docetaxel once every 3 weeks.
Patient demographic characteristics included: median age 67 years (range, 51~86), median ECOG performance status 1 (0~2), Gleason score ≥8 in 61 patients (86%), and median serum PSA 45.5 ng/mL (range, 3.7~2,420.0). A total of 405 cycles of treatment were administered with a median 6 cycles (range, 1~20) per patient. The median docetaxel dose-intensity was 24.4 mg/m2/week (range, 17.5~25.6). A PSA response was seen in 51% of 63 evaluable patients at 12 weeks and maximal PSA decline ≥50% in 59% of 70 evaluable patients. Tumor response was evaluated in 13 patients, 4 patients achieved PR, and 5 patients had SD with a response rate of 31%. With a median follow-up duration of 23.1 months (95%CI, 16.7~29.5), the median time to PSA progression was 5.1 months (95%CI, 4.5~5.8) and median overall survival was 22.8 months (95%CI, 16.6~29.1). Nine (13%) patients experienced grade 3 or higher febrile neutropenia.
This chemotherapy regimen (docetaxel every 3 weeks plus prednisolone daily) demonstrated a strong response in Korean patients with metastatic HRPC, while the toxicity profile was manageable and similar to that observed in Western patients.
Hormone-refractory prostate cancer; Chemotherapy; Docetaxel; Prednisolone; Febrile neutropenia
Radical nephrectomy with inferior vena cava (IVC) thrombectomy remains the most effective therapeutic option in patients with renal cell carcinoma and IVC tumor thrombus. Cephalic extension of the thrombus is closely related to perioperative morbidity. We purposed to design a safe and successful surgical strategy through a review of our surgical experience and treatment results in 35 patients (male:female=28:7, mean age=56 yr [32-77]) who underwent IVC thrombectomy with radical nephrectomy between January 1997 and December 2006. The limit of tumor extension was level I in 10 patients (28.6%), level II in 17 (48.6%), and level III and IV in 4 patients each (11.4%). Liver mobilization with hepatic vascular exclusion was performed in 12 patients and cardiopulmonary bypass in 7. Thirty-two primary closures, 2 patch closures, and 1 graft interposition were performed. One patient underwent simultaneous pulmonary embolectomy because of an operative pulmonary embolism. There was no operative mortality, and the overall survival at 5-yr was 50.8%. Complete thrombus removal without tumor fragmentation under long venotomy on fully exposed involved IVC is recommended for successful result in a bloodless operative field. The applicability of liver mobilization, hepatic vascular exclusion, and cardiopulmonary bypass, can be determined by the level of thrombus.
Vena Cava, Inferior; Thrombectomy; Kidney Neoplasms
The short-term safety and efficacy of zoledronic acid for the treatment of skeletal metastasis was evaluated in patients with hormone-refractory prostate cancer.
Patients and Methods
A total of 19 hormone-refractory prostate cancer patients with bone metastases were enrolled. All patients received up to six infusions of zoledronic acid (4 mg, given intravenously over 15 minutes, every 3 - 4 weeks). Safety was assessed by monitoring a`dverse events and serum creatinine levels. Efficacy was assessed by monitoring skeletal-related events, brief pain inventory score, quality of life score, type of pain medication, and analgesic score. Mean age of patients was 67.3 years (46 - 86 years), mean time from diagnosis of bone metastases was 27.6 months (0 - 117 months), and mean time from diagnosis of hormone-refractory disease was 7.5 months (0 - 26 months).
There was no clinically significant change in serum creatinine levels. Eleven adverse events (musculoskeletal disorders and systemic disorders) in 8 patients were classed as having a possible relationship to study drug. Fifteen patients completed six courses of zoledronic acid infusion. There were no significant changes in the brief pain inventory composite scores, quality of life questionnaire scores or analgesic score. No new skeletal-related events developed during the treatment period.
Zoledronic acid administered in this study as a 15-minute infusion demonstrated an acceptable and well-known safety profile in patients with refractory prostate cancer with bone metastases. However, prospective placebo-controlled clinical trials are required to elucidate the efficacy of zoledronic acid.
Prostatic neoplasms; neoplasm metastasis; zoledronic acid
We analyzed the prostate cancer data of 317 Korean men with clinically localized prostate cancer who underwent radical prostatectomy at Asan Medical Center between June 1990 and November 2003 to construct nomograms predicting the pathologic stage of these tumors, and compared the outcome with preexisting nomograms. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease (OCD), extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node metastasis (LNM) using serum prostate-specific antigen (PSA), Gleason score and clinical stage. Nomograms representing percent probabilities were constructed and compared with those presented by Partin et al. by calculating areas under the receiver operating characteristics (ROC) curves. Median serum PSA at surgery was 10.8 ng/mL, and median biopsy Gleason score was 7. Overall OCD, ECE, SVI and LNM rates were 59.6%, 20.5%, 11.7% and 8.2%, respectively, and areas under the curves were 0.724, 0.626, 0.662, and 0.794, respectively. Pathologic stage of localized prostate cancer in Korean men may be predicted using the Partin table, with acceptable accuracy for OCD and LNM, but less so for ECE and SVI.
Prostatic Neoplasms; Korean; Prediction; Comparison; Nomograms