Background
Pembrolizumab is effective in a limited number of patients with advanced urothelial carcinoma (UC). Therefore, we evaluated the prognostic value of clinical biomarkers following ...pembrolizumab treatment in patients with advanced UC.
Methods
We retrospectively reviewed the medical records of 121 patients with platinum-refractory advanced UC who received pembrolizumab. Inflammation-based prognostic scores before and 6 weeks after the treatment were recorded. The categorical variables influencing overall survival (OS) and objective response rate (ORR) were analyzed.
Results
Multivariate analyses showed that pretreatment Eastern Cooperative Oncology Group (ECOG) performance score (PS), presence of only lymph node metastasis (only LN mets), C-reactive protein (CRP), and neutrophil/lymphocyte ratio (NLR) were independent prognostic factors for OS (
P
= 0.0077; RR = 2.42,
P
= 0.0049; RR = 0.36,
P
= 0.0047; RR = 2.53, and
P
= 0.0079; RR = 2.33, respectively). The pretreatment risk stratification using ECOG PS, only LN mets, CRP, and NLR was used for estimating the OS (
P
< 0.0001) and ORR (
P
< 0.0001). Furthermore, changes in NLR in response to pembrolizumab were significantly associated with the OS (
P
= 0.0002) and ORR (
P
= 0.0023). This change was also significantly correlated with OS even in the high-risk group stratified by this pretreatment risk stratification (
P
= 0.0069).
Conclusions
This pretreatment risk stratification may be used for estimating the OS and ORR of patients with advanced UC treated with pembrolizumab. If changes in NLR in response to pembrolizumab treatment improve, pembrolizumab should be continued.
Background
Currently, there is no consensus regarding which patients with high-risk prostate cancer (PCa) would benefit the most by radical prostatectomy (RP). We aimed to identify patients with ...high-risk PCa who are treatable by RP alone.
Methods
We retrospectively reviewed data on 315 patients with D’Amico high-risk PCa who were treated using RP without neoadjuvant or adjuvant therapy at the institutions of the Yamaguchi Uro-Oncology Group between 2009 and 2013. The primary endpoint was biochemical progression-free survival (bPFS) after RP. Risk factors for biochemical progression were extracted using the Cox proportional hazard model. We stratified the patients with high-risk PCa into 3 subgroups based on bPFS after RP using the risk factors.
Results
At a median follow-up of 49.9 months, biochemical progression was observed in 20.5% of the patients. The 2- and 5-year bPFS after RP were 89.4 and 70.0%, respectively. On multivariate analysis, Gleason score (GS) at biopsy (≥ 8, HR 1.92,
p
< 0.05) and % positive core (≥ 30%, HR 2.85,
p
< 0.005) were independent predictors of biochemical progression. Patients were stratified into favorable- (0 risk factor; 117 patients), intermediate- (1 risk factor; 127 patients), and poor- (2 risk factors; 57 patients) risk groups, based on the number of predictive factors. On the Cox proportional hazard model, this risk classification model could significantly predict biochemical progression after RP (favorable-risk, HR 1.0; intermediate-risk, HR 2.26; high-risk, HR 5.03;
p
< 0.0001).
Conclusion
The risk of biochemical progression of high-risk PCa after RP could be stratified by GS at biopsy (≥ 8) and % positive core (≥ 30%).
Background
Patients with urinary bladder urothelial carcinoma (UC) with variant histology have features of more advanced disease and a likelihood of poorer survival than those with pure UC. We ...investigated the impact of variant histology on disease aggressiveness and clinical outcome after radical nephroureterectomy (RNU) in Japanese patients with upper tract UC (UTUC). Information on variant histology might guide appropriate patient selection for adjuvant therapy after RNU.
Methods
We enrolled 502 UTUC patients treated with RNU in this retrospective cohort study, and analyzed associations of variant histology with clinicopathological variables and disease-specific survival.
Results
The median follow-up was 41.4 months. A total of 60 (12.0 %) UTUC patients had variant histology. UTUC with variant histology was significantly associated with advanced pathological T stage (pT ≥ 3), higher tumor grade (G3), and more lymphovascular invasion (
P
< 0.0001). Variant histology in all patients was significantly associated with worse disease-specific survival after RNU on univariate analysis (
P
= 0.0004), but this effect did not remain significant on multivariate analysis. However, variant histology was a significantly independent predictor for disease-specific survival in patients with pT ≥ 3 tumors (
P
= 0.0095).
Conclusions
UTUC with variant histology might be a phenotype of high-grade, locally aggressive advanced tumors rather than of systemic disease. Variant histology may be useful for selection of patients with pT ≥ 3 UTUC for adjuvant therapy. Prospective studies in a larger number of patients with a centralized pathological review are needed to confirm our results.
Background
The standard of care for treatment of localized muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC). The patient’s condition may affect management of MIBC, especially for ...elderly patients with more comorbid conditions and lower performance status. We retrospectively evaluated the association between clinicopathological data and outcomes for patients with bladder cancer (BCa) treated by RC. We particularly focused on elderly patients (age ≥75 years) with BCa.
Methods
We enrolled 254 patients with BCa who underwent RC and urinary diversion with or without pelvic lymph node dissection. We assessed perioperative complications and clinicopathological data affecting overall survival (OS) after RC.
Results
The incidence of complications was 34.3 %, and that of severe complications (Grade 3–5) was 16.5 %. The elderly group experienced more severe complications (
P
= 0.042). Median follow-up was 43.0 months (range 1.0–155.6). Five-year OS after RC was 62.7 %. OS after RC was no different for patients aged ≥75 and <75 years (
P
= 0.983). Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) and hemoglobin (Hb) concentration were associated with all-cause mortality. Hb concentration of <12.6 g/dl was an independent predictor of a poor prognosis among elderly patients after RC for BCa. ECOG PS >1 tended to affect OS after RC in this group.
Conclusion
ECOG PS and preoperative Hb concentration were useful for prediction of clinical outcome after RC for elderly patients. This information may aid decision-making in the treatment of elderly patients with MIBC.
Objective: In this study, locally advanced bladder cancer was treated by radiation combined with cisplatin therapy and a retrospective analysis was conducted to predict the clinical response to ...chemoradiotherapy (CRT) based on the immunohistochemistry of apoptosis-related proteins. Methods: Sixty-two patients (median age, 68 years; range, 45–89 years) with transitional cell carcinoma of the bladder (pT1G3–pT4M0) treated with CRT (median dose: 40.5 Gy of radiation and 230 mg of cisplatin) were studied. Mucosal biopsy was performed before and after CRT. Paraffin-embedded tumor specimens were examined with TUNEL and were immunostained for Ki-67, p53, Bcl-2 and Bax; the Bax/Bcl-2 ratio and apoptosis index (AI) were calculated. Clinical features of the patients and response to CRT were compared with data obtained from examination of the tumors. Results: The 62 patients had a median follow-up period of 34 months (range, 3–84 months). Responses to CRT were as follows: CR, 34%; PR, 45%; NC, 21%. The survival rate of patients with Ki-67-positive tumors was significantly lower than those of patients with Ki-67-negative tumors (P < 0.05). No significant correlation was observed between the expression of any protein, the AI and the clinical response. However, the Bax/Bcl-2 ratio showed a significant association with the CR rate (P = 0.0289). Conclusions: The results of this study suggest that the combined assessment of Bcl-2 and Bax protein expression may be used to predict a clinical response to CRT based on the Bax/Bcl-2 ratio determined before therapy. The Ki-67 index may be a useful predictor of prognosis in patients treated by CRT.
Background
To verify the actual clinical benefit of docetaxel (DOC) therapy and to explore the prognostic factors that may predict overall survival in Japanese patients with castration-resistant ...prostate cancer (CRPC).
Methods
Baseline characteristics-matched CRPC patients who received conventional androgen-deprivation therapy (ADT) or ADT plus DOC were compared retrospectively. The primary endpoint was overall survival (OS) from primary therapy. Secondary endpoints were response of tumor(s), prostate-specific antigen (PSA) levels, and toxicity.
Results
Median OS was significantly longer in the DOC group (
n
= 117) than the control group (
n
= 118) (94.0 vs. 70.0 months,
P
= 0.0077) and the corresponding hazard ratio (HR) for death in DOC group was 0.566 95% confidence interval (95%CI) 0.370–0.867;
P
= 0.0088. Effective DOC groups medium dose (50–69 mg/m
2
) and high dose (≥70 mg/m
2
) had significantly longer median OS than control even when survival times were calculated from the start of castration-resistant events (151 vs. 36 months;
P
= 0.0173) and the corresponding HR for death in the DOC group was 0.515 (95%CI 0.293–0.903;
P
= 0.0205). In multivariate analysis, statistically significant prognostic indicators were Gleason score, time to CRPC events, and receipt of DOC therapy. Response rate of both measurable lesion and PSA was not significantly different between each DOC dose group. Grade 3 or 4 adverse events associated with low- 30–49 mg/m
2
, medium-, and high-dose DOC were 21.9, 35.7, and 90.7%, respectively. No death due to DOC therapy was reported.
Conclusion
Treatment with DOC improves OS from primary therapy compared with conventional ADT alone in Japanese patients with CRPC.
Recent studies have reported that centrosome hyperamplification (CH) is closely related to chromosomal instability in bladder cancer. In this study, we investigated whether CH could be used as a ...prognostic biomarker for patients with bladder cancer.
CH was evaluated by immunohistochemistry in 50 bladder cancers (< or =pT1: 43; > or =pT2: 7). In addition, numerical aberrations of chromosomes 7, 9, and 17 and gain of 20q13, on which the Aurora-A gene is located, were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed. Preliminary experiments on eight bladder cancer cell lines found that six had over 5% of CH cells associated with a gain of 20q13 and overexpression of Aurora-A; therefore, CH-positive cases (CH+) were defined as those having over 5% of cells with > or =3 centrosomes per cell.
CH+, 20q13 gain, chromosomal instability, and DNA aneuploidy were detected in 30 (60%), 18 (36%), 22 (44%), and 19 (38%) patients, respectively. There were significant differences in tumor number, grade, recurrence, and progression between the CH+ and CH- groups. The later had significantly higher recurrence-free and progression-free survivals than the former (P = 0.0028 and P = 0.0070, respectively, log-rank test). Multivariate analysis revealed that CH+ was the strongest predictor for tumor recurrence in nonmuscle invasive (pTa and pT1) bladder cancer (hazard ratio, 1.882; 95% confidence interval, 1.161-3.325; P = 0.0094).
Detection of CH may provide crucial prognostic information about tumor recurrence in bladder cancer.
It has been shown that the matrix metalloproteinase (MMP)-1 promoter polymorphism 1G/2G is associated with an increased risk of developing various cancers including renal cell carcinoma (RCC), and is ...in linkage disequilibrium (LD) with the MMP-3 promoter polymorphism 5A/6A. These two genes are localized in 11q22 adjacent to each other. However, the relationship between the MMP-3 5A/6A polymorphism and susceptibility to cancer remains ambiguous. In this study, we genotyped eight polymorphisms in the region containing the MMP-1 and MMP-3 genes in 177 healthy subjects, and explored the relationships between RCC and these polymorphisms or haplotypes in 156 RCC cases and 230 age- and gender-matched controls. All the subjects studied were of Japanese descent. There were three polymorphisms that showed stronger LD with the MMP-1 1G/2G promoter variant than with the MMP-3 5A/6A promoter variant. One of these three polymorphisms was present in exon 2 of the MMP-3 gene and caused an amino acid change, Glu45Lys (G/A). When the genotype distribution of Glu45Lys was compared between RCC patients and controls, the frequency of the G/G genotype was significantly higher in the patients age- and gender-adjusted odds ratio (OR) = 1.81, 95% confidence interval (CI) = 1.20–2.74. A significant increase in the frequency of the 2G/2G genotype of the MMP-1 1G/2G polymorphism was also observed in the patients (age- and gender-adjusted OR = 1.86, CI = 1.23–2.82), whereas there was no significant difference for the MMP-3 5A/6A polymorphism. As expected based on these genotype-level results, the frequency of the 2G-G haplotype of MMP-1 1G/2G and MMP-3 Glu45Lys (G/A) polymorphisms was significantly higher in the patients than in the controls (crude OR = 1.95, CI = 1.31–2.91). These findings suggest that this haplotype of MMP-1 and MMP-3 variants may be associated with the risk of developing RCC.
A recent report demonstrated that the deletion of chromosome 8p22 could predict disease progression in stage III (capsular penetrating) prostate cancer. We studied if the status of chromosomal ...deletions of 8p22 could reflect pathological stage as well as patient prognosis, thereby serving as a diagnostic tool to optimize the treatment strategy in prostate cancer.
A total of 97 patients (41 Japanese and 56 Swedish) were studied by the fluorescence in situ hybridization technique. Seventy-seven patients (23 pT2, 18 pT3, and 36 pN+ tumors) underwent surgery (radical prostatectomy or lymph node dissection). The specimens were prepared by touch biopsy. From another 20 cases, fine-needle aspiration biopsies were obtained.
8p22 deletions were detected in 47 (61%) and 11 (55%) specimens of 77 touch biopsies and 20 fine-needle aspiration biopsies, respectively. No significant difference was found in the frequency of 8p22 deletion between different preparations of specimens, as well as between different races (Japanese versus Swedish). The frequency of 8p22 deletion was statistically higher in patients with pT3 or more than in those with pT2 (P < 0.01). Disease progression was evaluated in 57 patients. The Cox proportional hazards model revealed 8p22 deletion to be the strongest parameter to predict disease progression (hazards ratio = 5.75; P = 0.0001).
Studies on chromosomal deletions of 8p22 by fluorescence in situ hybridization technique may serve as a genetic marker to optimize the treatment strategy in patients with prostate cancer to the optimal treatment.
Background
After radical nephroureterectomy (RNU), substantial numbers of patients with upper urinary tract urothelial carcinoma (UUT-UC) are ineligible for adjuvant chemotherapy owing to diminished ...renal function. Accurate preoperative prediction of survival is considered important because neoadjuvant chemotherapy may be as effective for high-risk UUT-UC as for muscle-invasive bladder cancer. We performed risk group stratification to predict survival based on specific preoperative factors.
Methods
We enrolled 536 UUT-UC patients treated with RNU in this retrospective cohort study and assessed preoperative clinical and laboratory variables influencing disease-specific survival.
Results
The median follow-up was 40.9 months. Using univariate analysis, tumor location; number of tumors; hydronephrosis; clinical T stage; clinical N category; voided urine cytology; neoadjuvant chemotherapy; hemoglobin; white blood cell (WBC) counts; and C-reactive protein had a significant influence on disease-specific survival (
P
< 0.05). Multivariate analysis revealed that clinical T stage, voided urine cytology, and WBC were independent predictors (
P
= 0.041,
P
= 0.020, and
P
= 0.017, respectively). We divided patients into three risk groups based on the number of the three independent predictors: 0, low risk; 1, intermediate risk; 2 and 3, high risk. Significant differences in disease-specific survival were found among these risk groups (
P
≤ 0.0047).
Conclusions
Our results suggest that risk group stratification based on preoperative clinical T stage, voided urine cytology, and WBC counts may be useful for selection of UUT-UC patients for neoadjuvant chemotherapy. Prospective studies with larger numbers of patients and a longer follow-up period are needed to confirm our results.
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