scholarly journals Oncological results of neoadjuvant chemohormonal therapy in patients with high and very high-risk prostate cancer

2020 ◽  
Vol 16 (1) ◽  
pp. 54-63
Author(s):  
M. V. Berkut ◽  
A. S. Artemjeva ◽  
S. A. Reva ◽  
S. S. Tolmachev ◽  
S. B. Petrov ◽  
...  

Tolsotogo St., Saint Petersburg 197022, RussiaBackground. Prostate cancer (PCa) of a high and very high risk is a potentially fatal disease that requires an active multimodal approach, including the use of neoadjuvant drug treatment. As option for this treatment is neoadjuvant chemohormonal therapy (NCHT) followed by radical prostatectomy (RPE). However, data on the oncological results of treatment of such patients are still limited and the role of neoadjuvant therapy in the treatment of high and very high-risk PCa remains not fully understood.Objective: to assess the oncological results of treatment patients with localized and locally advanced PCa of high and very high risk after NCHT. Materials and methods. This was a prospective randomized study: patients with PCa of high and very high-risk groups (prostate specific antigen levels (PSA) >20 ng/ml and/or Gleason score ³8 and/or clinical stage >T2c) were treated with RPE only (group RPE; n = 35) or NCHT followed by RPE (NCHT/RPE group; n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m2 up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6 subcutaneous injections every 28 days). After a follow-up examination evaluating the result of the neoadjuvant regimen, patients underwent RPE with extanded lymphadenectomy.Results. A mean follow-up was 37.08 ± 20.46 months. A statistically significant reduction of prostate specific antigen >50 % post-chemohormonal therapy was observed in all 36 cases. Lower postoperative stage was noticed in 38.5 % in NCHT/RPE group compared with 2.7 % in RPE group. Similarly, positive surgical margin rate was higher in group without neoadjuvant therapy – 40 and 25 % (RPE group). Cancerspecific survival was 97.2 % in NCHT/RPE group and 87.56 % in the RP group (p = 0.037), cancer specific survival rate – 91.4 % and 97.2 % respectively (log-rank test p = 0.22). At the same time, no statistically significant differences were obtained in 3-year recurrence free survival between groups: 38.8 % in NCHT/RPE group versus 43.6 % in the RPE group (log-rank test p = 0.36).Conclusion. Conducting NCHT before RPE is a safe and effective strategy in patients with PCa of high and very high risk groups and could improve oncological results.

Author(s):  
Juan José Montaño ◽  
Antoni Barceló ◽  
Paula Franch ◽  
Jaume Galceran ◽  
Alberto Ameijide ◽  
...  

Studies about the survival of patients with prostate cancer by stage or risk of progression are scarce. The aims of this study were (1) to determine the cause-specific survival by risk in prostate cancer patients in Mallorca diagnosed in the period 2006–2011; (2) to identify the factors that explain and predict the likelihood of survival and the risk of dying from this type of cancer; and (3) to determine the distribution of prostate cancer by risk in the patients in Mallorca diagnosed in the period 2006–2011. Incident prostate cancer cases diagnosed between 2006 and 2011 were identified through the Mallorca Cancer Registry. We collected age; date and method of diagnosis; date of follow-up or death; T, N, M and stage according to the TNM 7th edition; Gleason score; prostate-specific antigen (PSA); histology according to the International Classification of Diseases for Oncology (ICD-O) 3rd edition, comorbidities and treatments. We calculated risk in four categories: low, medium, high and very high. The end point of follow-up was 31 December 2014. Multiple imputation (MI) was performed to estimate cases with unknown risk. We identified 2921 cases. Five years after diagnosis, survival after MI was 89% globally, and was 100% for low-risk cases, 96% for medium risk, 93% for high risk and 69% for very-high-risk cases. Cases with histology other than adenocarcinoma, with high (and especially very high) risk, as well as with systemic, mixed and observation/unspecified treatments had worse prognoses.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5061-5061
Author(s):  
Matthew R. Cooperberg ◽  
Paul Brendel ◽  
Daniel J. Lee ◽  
Rahul Doraiswami ◽  
Hariesh Rajasekar ◽  
...  

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]


2021 ◽  
Author(s):  
Xianzhi Zhao ◽  
Yusheng Ye ◽  
Haiyan Yu ◽  
Lingong Jiang ◽  
Chao Cheng ◽  
...  

Abstract Objective To evaluate the efficacy and toxicity of SBRT for localized prostate cancer (PCa). Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China. Methods In this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray) from October 2012 to July 2019. Follow-up was performed every 3 months for evaluations of efficacy and toxicity. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 respectively. Factors predictive of bPFS were identified with COX regression analysis. Results 133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of the NCCN risk classification) with a median age of 76 years (range: 54–87 years) received SBRT. The median dose was 36.25Gy (range: 34-37.5Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6% respectively. Urinary symptoms were all alleviated after SBRT. All the patients tolerated SBRT with only 1 (0.8%) and 1 (0.8%) patient reporting grade-3 acute and late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis Conclusion SBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3199-3199
Author(s):  
Panagiotis Baliakas ◽  
Theodoros Moysiadis ◽  
Anastasia Hadzidimitriou ◽  
Aliki Xochelli ◽  
Mattias Mattsson ◽  
...  

Abstract The classification of CLL patients according to the somatic hypermutation status (SHM) of the immunoglobulin heavy variable (IGHV) genes, namely mutated (M-CLL) versus unmutated (U-CLL), reflects fundamental differences in disease biology and clinical course. Realizing this, here we followed a compartmentalized approach and addressed the issue of prognostication separately for M-CLL and U-CLL. In a multi-institutional cohort of 2366 patients [M-CLL, n=1364 (58%); U-CLL, n=1002 (42%)] consolidated within ERIC, the European Initiative in CLL, we assessed the clinical impact of 'traditional' (age and clinical stage at the time of diagnosis, gender, CD38 expression, FISH detected abnormalities included in the Döhner hierarchical model of cytogenetic aberrations), and novel prognosticators (recurrent mutations within the TP53, SF3B1, NOTCH1, MYD88, and BIRC3 genes; IGHV gene usage; membership in stereotyped subsets) within M-CLL and U-CLL. Our statistical approach was based both on Cox regression models and recursive partitioning algorithms; internal validation was performed via bootstrapping procedures. Given the retrospective nature of our study, time-to-first-treatment (TTFT) was the primary endpoint. As expected, M-CLL exhibited significantly longer TTFT compared to U-CLL [median TTFT: not yet reached (M-CLL) vs 1.9 years (95% CI: 0.01-12.3 years, U-CLL), p<0.0001]. Advanced clinical stages (Binet B-C) were associated with shorter TTFT in both M-CLL and U-CLL; a significantly worse outcome was also identified for Binet C versus Binet B cases (p<0.0001). Binet A patients received our special focus, representing 90% and 67% of M-CLL and U-CLL studied cases, respectively. Amongst Binet A M-CLL cases, TP53 aberrations [TP53abs, deletions of chromosome 17p, del(17p) and/or TP53 mutations], stereotyped subset #2 membership and trisomy 12 were identified as equally adverse prognostic indicators [median TTFT: 5.5 (95% CI: 0.2-12.8), 4 (95% CI: 0.6-6.8) and 7.3 (95% CI: 0.7-13.4) years, respectively; p-value: non-significant when applying the log-rank test for all paired comparisons); of note, TP53abs were mutually exclusive with the other two features. Amongst Binet A U-CLL cases, TP53abs, SF3B1 mutations and deletion of chromosome 11q [del(11q)] had an overall similar adverse impact [median TTFT for TP53abs, SF3B1 mutations and del(11q): 1.8 (95% CI: 0.01-4.4), 2 (95% CI: 0.01-7.7) and 2.1 (95% CI: 0.01-8.1) years, respectively, p-value: non-significant when applying the log-rank test for all paired comparisons]. Within the remaining Binet A U-CLL cases [i.e. those lacking TP53abs and/or SF3B1 mutations and/or del(11q)], the only parameter associated with shorter TTFT was male gender (median TTFT: 3.5 years, 95% CI: 0.5-8.1 years). Based on these findings, we developed two prognostic indices for assessing TTFT tailored specifically to M-CLL and U-CLL, respectively. Within M-CLL (Figure 1A), 4 subgroups were identified: (i) very high risk: Binet C with identical 5- and 10-year treatment-probability (TP) of 92%; (ii) high risk: Binet B, 5y-TP and 10y-TP: 64% and 84%, respectively; (iii) intermediate risk: Binet A with one of the following: TP53abs or +12 or subset #2 membership, 5y-TP and 10y-TP: 40% and 55%, respectively; and (iv) low risk: Binet A nonTP53abs/+12/subset#2, 5y-TP and 10y-TP: 12% and 25%, respectively. Within U-CLL (Figure 1B), 5 subgroups were identified: (i) very high risk: Binet C with 5- and 10-year TP of 100%; (ii) high risk: Binet B, identical 5y-TP and 10y-TP: 90% and 100%, respectively; (iii) intermediate risk: Binet A with one of the following: TP53abs or SF3B1 mutations or del(11q), 5y-TP and 10y-TP: 78% and 98%, respectively; (v) low risk: Binet A, male nonTP53abs/SF3B1mut/del(11q), 5y-TP and 10y-TP: 65% and 85%, respectively and (iv) very low risk: Binet A, female nonTP53abs/SF3B1mut/del(11q), 5y-TP and 10y-TP: 45% and 65%, respectively. In conclusion, we identified clinicobiological parameters with distinct prognostic implications for M-CLL and U-CLL. These parameters were used in order to develop prognostic indices tailored to SHM status that were found capable of distinguishing subgroups with markedly different outcomes. We argue that such a compartmentalized approach may supersede previous attempts, thus overcoming the pronounced heterogeneity of CLL and optimizing prognostication. PB and TM contributed equally as first authors Figure 1 Figure 1. Disclosures Rosenquist: Gilead Sciences: Speakers Bureau.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 177-177
Author(s):  
Takamitsu Inoue ◽  
Norihiko Tsuchiya ◽  
Shigeyuki Matsui ◽  
Tomomi Kamba ◽  
Koji Mitsuzuka ◽  
...  

177 Background: Individual genetic variations may have a significant influence on the survival of metastatic prostate cancer (PCa) patients. We aimed to identify target genes and their variations involved in the survival of PCa patients using a single nucleotide polymorphism (SNP) panel. Methods: A total of 185 PCa patients with bone metastasis at initial diagnosis were analyzed. Each patient was genotyped using a Cancer SNP panel that contained 1421 SNPs in 408 cancer-related genes. SNPs associated with the survival were screened by log rank test. A prognostic scoring index using selected SNPs was developed by incorporating the difference in their effect sizes to classify high-risk and low-risk groups and its predictive accuracy was assessed. Results: Fourteen SNPs in six genes, XRCC4, PSM1, GATA3, IL13, CASP8, and IGF1, were identified to have statistically significant association with the cancer-specific survival. The cancer-specific survivals of patients grouped according to the number of risk genotypes of 6 SNPs selected from the 14 SNPs differed significantly (0-1 vs 2-3 vs 4-6 risk genotypes, P = 7.20×10−8). The predictive model using the 14 SNPs showed a statistically significant cross-validated accuracy in predicting the groups at high and low risk groups for poor survival (P = 0.0050). The high-risk group was independently associated with the survival in a multivariate analysis that included conventional clinicopathological variables (P = 0.0060). Conclusions: Using a panel of the SNPs, the prediction of the survival and optimization of the individualized treatment for patients with advanced PCa may be possible.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 103-103
Author(s):  
Jeffrey J. Tosoian ◽  
Debasish Sundi ◽  
Brian Francis Chapin ◽  
Emmanuel S. Antonarakis ◽  
Meera Chappidi ◽  
...  

103 Background: Beginning in 2014, the National Comprehensive Cancer Network (NCCN) recognized very high-risk (VHR) prostate cancer (cT3b-T4, or primary Gleason pattern 5, or more than 4 biopsy cores with Gleason score 8-10, or multiple HR features) as a classification distinct from high-risk (HR) disease. Using prospectively collected institutional data, we describe contemporary treatment patterns and short-term outcomes in the VHR population. Methods: Men who underwent radical prostatectomy (RP) between January 2010 and June 2015 were identified using the Johns Hopkins RP database, and trends in management were compared across the study period. Pathological and short-term clinical outcomes were assessed in men with VHR cancer. Non organ-confined disease (NOCD) was defined as ≥ pT3 disease or lymph node positivity, persistent postoperative PSA as ≥ 0.2 ng/mL, and biochemical recurrence (BCR) as a PSA ≥ 0.2 ng/mL following an initial undetectable postoperative PSA. Results: During the study period, 4,954 men underwent RP, of which 161 (3.2%) men had VHR cancer at diagnosis. The annual proportion of men who underwent RP with VHR cancer increased over the study period (chronologically 1.8%, 1.0%, 3.3%, 4.1%, 5.6%, and 5.2%; p<0.001). Sixteen percent of men with VHR disease were enrolled in pre-surgical clinical trials, with an increase from 0% of men in 2010 to 19.1% in 2015 (p=0.11). At RP, 39% of the VHR cohort had seminal vesicle invasion, 26% had lymph node involvement, and a total of 74% had NOCD. Following surgery, 33% of men had PSA persistence, and 40% experienced either PSA persistence or BCR during follow-up (median 13.4 months). Of 136 men with at least one follow-up assessment, 15 (11.0%) developed metastasis; 33% of the cohort was treated with radiation therapy, 42% with androgen deprivation, and 15% with docetaxel. Conclusions: The VHR population carries the greatest risk of clinical progression following local treatment. Over the past five years, we have observed increasing surgical treatment and clinical trial enrollment at our institution. Continued assessment of post-operative interventions and outcomes will help to facilitate counseling and establish point estimates from which to power clinical trials.


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 333-333
Author(s):  
Howard M. Sandler ◽  
Theodore Karrison ◽  
A. Oliver Sartor ◽  
Leonard G. Gomella ◽  
Mahul B. Amin ◽  
...  

333 Background: High-risk, localized prostate cancer has a poor prognosis. We hypothesized that adj docetaxel (D) and prednisone and long-term (24 mos) androgen suppression (AS) and radiation therapy (RT) would improve overall survival (OS) and tested this in NRG/RTOG 0521. Results with med follow-up of 5.7 yrs were reported (JCO 37:1159, 2019), showing a benefit of D (HR=0.69, 90% CI: 0.49-0.97, 1-sided p=0.034). Med follow-up is now 10.4 yrs and we report updated results for OS and metastasis (DM). Methods: NRG/RTOG 0521 opened 12/05 and closed 8/09 with targeted accrual of 600 and designed to detect a HR of 0.49, based on improvement in 4-yr OS from 86 to 93%. With 0.05 1-sided type I error and 90% power >78 deaths were required. Pts were stratified by predefined risk groups. Group 1: Gl 9-10, any T; Group 2: Gl 8, PSA<20, T≥T2; Group 3: Gl 8, PSA≥20, any T; Group 4: Gl 7, PSA≥20, any T. maxPSA ≤150. RT dose was 75.6 Gy. Chemo consisted of 6, 21-day cycles of D starting 28 days after RT. Results: Of 612 accrued, 563 were eligible/available for analysis. By risk group 1-4, there were 297, 116, 64, and 86 pts. Med PSA 15 ng/mL. 10-yr OS rates were 64% [95% CI: 58-70%] for AS+RT and 69% [95% CI: 63-75%] for AS+RT+CT (HR = 0.89, 90% CI: 0.70, 1.13, 1-sided p=0.22). However there was evidence of non-proportional hazards (Grambsch-Therneau test, p=0.016). Thus survival was alternatively evaluated with restricted mean survival time (RMST). The difference in RMST at 10 yrs was 0.42 yrs (90% CI: 0.07-0.77, 2-sided p=0.048). Cumulative incidence of DM at 10 yrs was 22% [95% CI: 17-27%] for AS+RT and 20% [95% CI: 15-25%] for AS+RT+CT (2-sided log-rank p=0.29). At 10 years most deaths occurred in risk group 1: 62 in AS+RT and 50 in AS+RT+CT (HR= 0.93, 95% CI: 0.66-1.32, 2-sided log-rank p=0.16). There was no new related Grade 5 toxicity. Conclusions: OS findings, reported after follow-up of 5.7 yrs, demonstrated a small beneficial effect of adding D to AS and RT. With longer follow-up the benefit of D remains, but the HR varies over time and the OS curves have converged. Support: U10CA180868 (NRG Operations), U10CA180822 (NRG SDMC), U24CA180803 (IROC) from the NCI and Sanofi-Synthelabo Int. Clinical trial information: NCT00288080.


2020 ◽  
Author(s):  
Na Li ◽  
Xiaoling Chen ◽  
Chang Liu ◽  
Yong Feng ◽  
Xiaoqiang Sun ◽  
...  

Abstract Background: The tumor microenvironment plays a vital role in tumor biology and has recently attracted widespread attention. However, the prognostic significance of integrated immune scores in lung adenocarcinoma has not yet been identified. This study aimed to systematically estimate the association between immune scores and prognosis and develop a clinical nomogram to predict the survival of patients with lung adenocarcinoma. This study also systematically explored the underlying prognostic factors of the immune score in lung adenocarcinoma.Methods: Public datasets for lung adenocarcinoma was acquired from The Cancer Genome Atlas data portal. The immune score of each sample was calculated using the ESTIMATE algorithm. Univariate and multivariate Cox regression analyses identified several significant prognostic factors and further developed a prognostic nomogram. The C-index, calibration curve, and ROC curve were used to evaluate the predictive accuracy and discriminative ability of the resultant nomogram. Results: We found that patients with higher immune scores had a better prognosis (log rank test p = 0.0004). The nomogram that integrated the immune score could effectively stratify high-risk LUAD patients in terms of clinical response. Patients in the high-risk groups usually had a worse prognosis (log rank test p < 0.0001) and higher mortality. The mortality rate in high and low risk groups was 42.67% and 26.37%, respectively (p < 0.0001). In addition, correlation analysis showed that the immune score was significantly dependent on the mRNA expression of immunotherapy-associated biomarkers (PD-1, PD-L1, and LAG3) as well as on the presence of certain immune cell subtypes, but had no correlation with tumor mutation burden.Conclusion: The immune score is a prognostic factor in lung adenocarcinoma. The nomogram with an integrated immune score can effectively predict the survival of patients with lung adenocarcinoma. The mechanism by which the immune score estimates the prognosis of patients with lung adenocarcinoma is related to the tumor immune microenvironment.


Sign in / Sign up

Export Citation Format

Share Document