Association of tumor burden with the eligibility of upfront therapy in patients with castration-naive prostate cancer: A multicenter retrospective study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 107-107
Author(s):  
Hiromichi Iwamura ◽  
Shingo Hatakeyama ◽  
Shintaro Narita ◽  
Toshihiko Sakurai ◽  
Sadafumi Kawamura ◽  
...  

107 Background: Although several large-scale studies reported a robust benefit of upfront therapy for mHNPC, not all patients with mHNPC experienced mCRPC progression. As there is a concern for overtreatment in patients with low-risk/volume disease, we aimed to identify potential candidates for upfront therapy in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: We retrospectively evaluated 679 patients with mHNPC who were initially treated with conventional androgen deprivation therapy. We defined the patients with progression to metastatic castration-resistant prostate cancer (mCRPC) as potential candidates for upfront therapy. To estimate the suitable candidate for upfront therapy, we retrospectively compared mCRPC progression rate, mCRPC-free survival, and overall survival (OS) after castration-resistance (OS-CR) between the low- and high-volume disease groups. Furthermore, we tried to develop a novel prediction model using deep learning algorithm. Results: The number of patients with mCRPC progression (potential candidates for upfront therapy) was 119 (52%) and 319 (71%) in the low- and high-volume disease groups. The mCRPC progression rate and CRPC-free survival were significantly worse in high-volume disease group ( P < 0.01), but no difference was found for OS-CR. Multivariate Cox regression analysis showed no significant association between tumor volume and OS-CR (HR 1.14, P=0.52). The deep learning model showed not high accuracy of mCRPC prediction (AUC 0.66). Conclusions: Approximately a half of patients with low-volume disease had progression to mCRPC. As the OS-CR in the patients with low-volume disease showed poor prognosis as well as those with high-volume disease, upfront therapy may be needed for a half of patients with low-volume disease.

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Takashi Kawahara ◽  
Shuko Yoneyama ◽  
Yoshio Ohno ◽  
Junpei Iizuka ◽  
Yasunobu Hashimoto ◽  
...  

Background. The CHAARTED and LATITUDE trials demonstrated a prolonged overall survival (OS) for metastatic hormone-naïve prostate cancer (mHNPC) patients who receive up-front docetaxel or abiraterone acetate. These studies used their own risk criteria: CHAARTED trial defines high- and low-volume diseases and LATITUDE trial targeting a high-risk disease. The present study explored whether or not the CHAARTED and LATITUDE criteria were useful for predicting the outcome in Japanese bone mHNPC patients, including elderly patients (≥70 years). Methods. A total of 532 mHNPC patients diagnosed from 2004 to 2014 in multithird referral cancer centers were enrolled in this study. All patients had bone metastasis and received combined androgen blockade treatment as an initial hormonal therapy. Results. The number of patients with CHAARTED low-volume and high-volume diseases was 178 (33.5%) and 354 (66.5%), respectively. On the contrary, the number of patients with LATITUDE low-risk and high-risk diseases was 157 (29.5%) and 375 (70.5%), respectively. A total of 307 (57.7%) patients were defined as having both CHAARTED high-volume and LATITUDE high-risk disease. The median castration-resistant prostate cancer- (CRPC-) free survival was 12.5 months for the CHAARTED high volume, 56.9 months for the CHAARTED low volume, 13.6 months for the LATITUDE high risk, and 37.3 months for the LATITUDE low risk, respectively. The OS was 50.1 months in patients with CHAARTED high-volume disease, 95.1 months in patients with CHAARTED low-volume disease, 54.0 months in patients with LATITUDE high-risk disease, and 92.7 months in patients with LATITUDE low-risk disease, respectively. This trend was also observed in elderly (≥70 years old) patients. Conclusions. The patients with CHAARTED high-volume disease or LATITUDE high-risk disease showed a shorter CRPC-free survival and a shorter OS than those in the CHAARTED low-volume disease group or in the LATITUDE low-risk group among Asian Japanese bone metastatic HNPC patients.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 213-213
Author(s):  
Teppei Okamoto ◽  
Shingo Hatakeyama ◽  
Masahiro Takahashi ◽  
Shintaro Narita ◽  
Masanori Ishida ◽  
...  

213 Background: To evaluate the prognostic impact of time to castration resistance (TCR) in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: We retrospectively evaluated 283 mHNPC patients with metastatic castration-resistant prostate cancer (mCRPC) who were initially treated with androgen deprivation therapy as metastatic hormone-naïve prostate cancer in 14 hospitals between September 2008 and October 2018. Overall survival (OS) and OS after castration resistance (OS-CR) were compared between the <12 months (TCR <12M) and ≥12 months (TCR ≥12M). The association between the first-line life-prolonging therapy (docetaxel or new androgen receptor-targeted agents: ART) and TCR on OS-CR was investigated using multivariate Cox regression analysis via inverse probability of treatment weighting (IPTW) model. Results: Median age and time to CRPC were 72 years and 12 months, respectively. The number of patients in the TCR<12M and ≥12M groups were 137 and 146, respectively. Of 283, baseline parameters such as age, extent of disease (EOD), hemoglobin (Hgb), lactate dehydrogenase (LDH), and serum albumin levels were significantly differences in between the groups. We observed significantly poor OS and OS-CR in the TCR <12M group than those in the TCR ≥12M group. First-line docetaxel therapy did not significantly improved OS-CR regardless of TCR. Background (age, ECOG PS, GS, Hgb, tumor volume, serum data, and TCR)-adjusted multivariate Cox regression analyses showed that first-line docetaxel therapy was significantly associated with shorter OS-CR than first-line ART therapy in the TCR <12M group. Conclusions: The prognostic impact of TCR on OS was significant. However, the association between the first-line life-prolonging therapy and TCR on OS need further study.


2021 ◽  
Author(s):  
Jialin Meng ◽  
Zichen Bian ◽  
Chenyu Zhu ◽  
Zhi Tao ◽  
Xiaoyan Jin ◽  
...  

Abstract Background: We aimed to establish and validate a coagulation-feature-based nomogram to predict recurrence-free survival for prostate cancer patients.Methods: The study contained 168 prostate cancer patients who had received radical prostatectomy between 2012 and 2018. The Kaplan-Meier plot and log-rank analysis were used to screen recurrence-free survival-related features. The nomogram was established by combining the significant coagulation features with clinicopathological characteristics by using Cox regression analysis. The accuracy and clinical significance of the nomogram model were assessed by receiver operating characteristic (ROC) curve, Kaplan-Meier plot, and calibration plot. Besides, we explored the correlation between coagulation pathway activity and patients’ prognosis based on public datasets by using gene set variation analysis (GSVA) analysis.Results: The results suggested that patients in the high-risk subgroup showed unfavorable prognoses than those in the low-risk subgroup classified by the nomogram model in both the training (log-rank P < 0.0001) and validation (log-rank P = 0.0004) cohorts. The nomogram model exhibited high discriminative accuracy in the training cohort [1-year area under the curve (AUC) of 0.74, and 3-year AUC of 0.69], which was confirmed in the internal validation cohort (C-index = 0.651). Besides, the calibration plots confirmed good concordance for the prediction of recurrence-free survival at 1 and 3 years. Besides, the subgroup analyses confirmed the usage of this model in different clinicopathological subgroups. Finally, GSVA analyses suggested that patients with higher coagulation pathway scores mostly had unfavorable prognoses than those with lower scores, a result consistent with the findings obtained above.Conclusions: In conclusion, we develop a practical nomogram model for the recurrence-free survival predicting of prostate cancer patients. This model may offer clinicians prognostic assessments and facilitate personalized treatment.


2021 ◽  
Vol 11 ◽  
Author(s):  
Waseem Masalha ◽  
Dieter Henrik Heiland ◽  
Christine Steiert ◽  
Marie T. Krüger ◽  
Daniel Schnell ◽  
...  

ObjectiveSpheno-orbital meningiomas (SOM) are rare intracranial tumors that arise at the sphenoid wing. These tumors can invade important neurovascular structures making radical resection difficult, while residual tumors often lead to recurrence. The purpose of this study was to evaluate prognostic factors influencing the recurrence and progression-free survival (PFS) rates of spheno-orbital meningiomas, with a particular focus on the role of surgery and postoperative radiotherapy.MethodsBetween 2000 and March 2020, 65 cases of spheno-orbital meningioma were included, of which 50 cases underwent surgical treatment alone, and 15 cases underwent resection and radiotherapy. A Kaplan-Meier analysis was performed to provide median point estimates and PFS rates; further, Cox regression analysis was used to identify significant factors associated with treatment.ResultsGross total resection significantly reduced the risk of recurrence (p-value = 0.0062). There was no significant benefit for progression-free survival after postoperative radiotherapy (p-value = 0.42). Additionally, spheno-orbital meningiomas with an invasion of the cavernous sinus and intraconal invasion showed significantly worse PFS compared to other locations (p-value = 0.017).ConclusionThe maximal safe resection remains the most important prognostic factor associated with lower recurrence rates and longer PFS in patients with spheno-orbital meningioma. The invasion of the cavernous sinus and intraconal invasion was an independent factor associated with worse PFS. Patients with postoperative high-precision radiotherapy did not show significantly better PFS due to the small number of patients.


2019 ◽  
Vol 47 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Francesco Pasqualetti ◽  
Marco Panichi ◽  
Martina Sollini ◽  
Aldo Sainato ◽  
Luca Galli ◽  
...  

Abstract Background In the last years, functional imaging has given a significant contribution to the clinical decision-making of biochemically relapsed prostate cancer (PCa). Hereby, we present a prospective study aiming to validate the role of [18F]Fluoro-Methyl Choline ([18F]FMCH) PET/CT in the selection of PCa patients suitable for stereotactic body radiotherapy (SBRT). Methods Patients with biochemical recurrence limited up to three lesions revealed by [18F]FMCH PET/CT were enrolled in the present study and treated with SBRT on all active lesions. Systemic therapy-free survival since the [18F]FMCH PET/CT was considered as the primary endpoint. Results Forty-six patients were evaluated, and a total of 67 lesions were treated. After a median follow-up of 28.9 months, systemic therapy was started in 30 patients (65.2%) and median systemic therapy-free survival was 39.1 months (95% CI 6.5–68.6); 6, 12, and 24-month ratios were 93.5%, 73.9%, and 63.1%, respectively. At univariate Cox regression analysis, Delta PSA demonstrated an impact on systemic therapy-free survival (p < 0.001). Conclusions Based on our findings, [18F]FMCH PET/CT can identify oligometastatic prostate cancer patients suitable for SBRT, resulting in a systemic therapy-free survival of 39.1 months.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhihao Zou ◽  
Ren Liu ◽  
Yingke Liang ◽  
Rui Zhou ◽  
Qishan Dai ◽  
...  

BackgroundProstate cancer (PCa) is the most common malignant male neoplasm in the American male population. Our prior studies have demonstrated that protein phosphatase 1 regulatory subunit 12A (PPP1R12A) could be an efficient prognostic factor in patients with PCa, promoting further investigation. The present study attempted to construct a gene signature based on PPP1R12A and metabolism-related genes to predict the prognosis of PCa patients.MethodsThe mRNA expression profiles of 499 tumor and 52 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. We selected differentially expressed PPP1R12A-related genes among these mRNAs. Tandem affinity purification-mass spectrometry was used to identify the proteins that directly interact with PPP1R12A. Gene set enrichment analysis (GSEA) was used to extract metabolism-related genes. Univariate Cox regression analysis and a random survival forest algorithm were used to confirm optimal genes to build a prognostic risk model.ResultsWe identified a five-gene signature (PPP1R12A, PTGS2, GGCT, AOX1, and NT5E) that was associated with PPP1R12A and metabolism in PCa, which effectively predicted disease-free survival (DFS) and biochemical relapse-free survival (BRFS). Moreover, the signature was validated by two internal datasets from TCGA and one external dataset from the Gene Expression Omnibus (GEO).ConclusionThe five-gene signature is an effective potential factor to predict the prognosis of PCa, classifying PCa patients into high- and low-risk groups, which might provide potential novel treatment strategies for these patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Alexander Kretschmer ◽  
Johanna Milow ◽  
Chukwuka Eze ◽  
Alexander Buchner ◽  
Minglun Li ◽  
...  

IntroductionThe role of salvage lymph node dissection (SLND) and radiotherapy (SLNRT) in the management of nodal-only recurrent prostate cancer (PC) remains controversial. In addition, impact on health-related quality of life (HRQOL) has not been adequately evaluated yet.Materials and MethodsAnalysis was limited to patients that were diagnosed with nodal-only recurrent PC via PSMA-PET/CT. SLND was performed via open approach. For SLNRT, dose regimens were normo- or slightly hypo-fractionated with a simultaneous boost to the PET-positive recurrences. EORTC QLQ-C30 and PR-25 questionnaires were used to assess HRQOL. Continence status was assessed using daily pad usage and the validated ICIQ-SF questionnaire. For multivariable analysis, Cox regression models were used (p&lt;0.05).Results138 patients (SLND: 71; SLNRT: 67) were included in the retrospective analysis. Median follow-up was 47 months (mo) for SLNRT patients (IQR 40–61), and 33mo for SLND patients (IQR 20–49; p&lt;0.001). In total, 61 patients (91.0%) in the SLNRT cohort and 43 patients (65.2%; p&lt;0.001) in the SLND cohort underwent ADT anytime during the follow-up period. In multivariate Cox regression analysis, SLNRT could be confirmed as an independent predictor for increased PSA progression-free survival (PFS; HR 0.08, 95%CI 0.040 – 0.142, p&lt;0.001). Estimated median metastasis-free survival (MFS) was 70mo for the total cohort without statistically significant differences between both subgroups (p=0.216). There were no significant differences regarding general HRQOL, daily pad usage, and ICIQ-SF scores between the respective cohorts.ConclusionsIn a large contemporary series of patients with nodal-only recurrent PC based on PSMA-PET/CT staging, we observed significantly increased PSA PFS in patients undergoing SLNRT while no significant differences could be observed in MFS, and functional outcomes including HRQOL.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 137-137
Author(s):  
David Pfister ◽  
Friederike Haidl ◽  
Tim Nestler ◽  
Pia Paffenholz ◽  
Axel Heidenreich

137 Background: Improved imaging modalities identify metastatic prostate cancer earlier. Atypical and oligometastatic disease is identified more often. Thus a more individual treatment approach in oligometastatic prostate cancer is getting more popular. We demonstrate our results in recurrent disease in seminal vesical remnants after radical prostatectomy and radiotherapy. Methods: A total of 33 patients underwent open resection of locoregional recurrence in seminal vesicals. In case of suspicious 68Ga-PSMA-PET findings in the small pelvis an additional ipsilateral lymph node dissection was performed in 10 patients. 11 patients already received hormone treatment fulfilling the definition of castration resistant prostate cancer. Age, PSA-DT, PSA, time to recurrence after primary treatment resection status were used in a uni and multivariate-cox regression analysis for biochemical relapse after surgery. Results: Median patient age at time of salvage surgery was 70(57-77) years. Median PSA and PSA-DT was 2.79(0.4-61.54)ng/ml and 5.4(1.6-20.1)months respectively. Median surgical time and hospital stay was 132 (75-313)min and 5.5(4-13)days. Median progression-free survival was 29 (8-47) months. After a mean follow-up of 22 months (3-68) months three patients died 8, 14, and 40 months after salvage surgery. In a univariable cox-regression analyses age at time of surgery, preoperative PSA and the time from primary treatment to salvage surgery have been identified as significant parameters for biochemichal relapse. Only the interval from primary to salvage surgery was significant with a Hazard ratio of 1.008 (95%-CI 1.001-1.015, p=0,018) in multivariate analysis. 4 adjunctive surgeries (Ureterovericoneostomy n=3 and one nephrectomy) were needed due to local progressive disease. Conclusions: Seminal vesicle resection is feasible with no significant intra and postoperative complications even in CRPC. Although there is a good median progression-free survival after 5 years almost all patients had biochemical or systemic relapse. Salvage surgery must be seen as prevention for local symptoms, to our experience most often postrenal ipsilateral obstruction.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 917
Author(s):  
Jun A ◽  
Baotong Zhang ◽  
Zhiqian Zhang ◽  
Hailiang Hu ◽  
Jin-Tang Dong

Molecular signatures predictive of recurrence-free survival (RFS) and castration resistance are critical for treatment decision-making in prostate cancer (PCa), but the robustness of current signatures is limited. Here, we applied the Robust Rank Aggregation (RRA) method to PCa transcriptome profiles and identified 287 genes differentially expressed between localized castration-resistant PCa (CRPC) and hormone-sensitive PCa (HSPC). Least absolute shrinkage and selection operator (LASSO) and stepwise Cox regression analyses of the 287 genes developed a 6-gene signature predictive of RFS in PCa. This signature included NPEPL1, VWF, LMO7, ALDH2, NUAK1, and TPT1, and was named CRPC-derived prognosis signature (CRPCPS). Interestingly, three of these 6 genes constituted another signature capable of distinguishing CRPC from HSPC. The CRPCPS predicted RFS in 5/9 cohorts in the multivariate analysis and remained valid in patients stratified by tumor stage, Gleason score, and lymph node status. The signature also predicted overall survival and metastasis-free survival. The signature’s robustness was demonstrated by the C-index (0.55–0.74) and the calibration plot in all nine cohorts and the 3-, 5-, and 8-year area under the receiver operating characteristic curve (0.67–0.77) in three cohorts. The nomogram analyses demonstrated CRPCPS’ clinical applicability. The CRPCPS thus appears useful for RFS prediction in PCa.


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