Low-intermediate Risk Disease Research Articles

Does larger prostate size provide protection for cancer specific outcomes in localized prostate cancer.

Benign prostatic hyperplasia is common in the aging population and frequently comorbid with localized prostate cancer. Large prostate volume places significant challenges in robotic prostatectomy including reduced mobility and visualization. The goal of this study is to evaluate the effect of prostate volume as a continuous variable on cancer specific outcomes. Three thousand four hundred and twenty five patients with localized prostate cancer at a single institution who underwent robotic prostatectomy were retrospectively reviewed. A number of preoperative, operative, and postoperative variables were collected to evaluate cancer specific outcomes including pathologic stage, tissue margins, and biochemical recurrence (BCR). Logistic regression models and univariate and multivariate analyses were implemented for pathologic stage T3 and BCR respectively. The median follow up time was 52 months (IQR 18-95). 37.4% of the patients had a final pathologic stage of T3 or higher, 21.2% experienced positive surgical margins, and 24.7% of patients experienced BCR. Prostate size was a significant predictor of all three outcomes of interest. Increasing prostate size was protective against both higher pathologic stage and positive surgical margins (odds ratio = 0.989, 0.990 respectively, p < 0.001). There was a modest increase in the risk of BCR with increasing gland size (hazard ratio = 1.006, p < 0.001). These results were most significant for patients with Gleason Grade Groups 1 and 2 prostate cancer. Prostate size is a commonly determined clinical factor that effects both surgical planning and cancer specific outcomes. Increasing prostate size may offer protection against higher stage disease and positive surgical margins. While surgically challenging, favorable oncologic outcomes can be consistently achieved for patients with low-intermediate risk disease.

Use of Pre-Transplant Minicog Cognitive Impairment Screening and Validation of Frailty and Functionality Assessment Prior to Allogeneic Hematopoietic Stem Cell Transplantation

Background: We demonstrated that impaired functionality and frailty have a negative impact on survival after allogeneic hematopoietic cell transplantation (HCT) (Salas et al., 2019). This impact is independent of other predictive models including HCT comorbidity index (HCT-CI) and disease risk index (DRI). Cognitive changes are frequently reported among survivors of autologous and allogeneic HCT. However, impact of the presence of cognitive impairment prior to allogeneic HCT has not been studied. We hypothesized that the presence of cognitive impairment before transplantation could have a negative effect on the outcomes of allogeneic HCT. Patients and methods: We evaluated transplant outcomes of 277 patients who underwent our updated frailty assessment including the MiniCog scale, incorporated as standard of care in April 2020. The MiniCog assessment included recalling of three unrelated words, for a total of three points and drawing of a clock with the face, number and hands indicating a specific time, for a total of 2 points. We used the cutoff score of &amp;lt;3 as a marker of cognitive impairment and evaluated the effect of cognitive impairment on: overall survival (OS), relapse free survival (RFS), non-relapse mortality (NRM). We further sought to validate our previously described frailty scale in prediction of transplant outcomes, including OS, RFS, and NRM, in the new cohort and compare its performance in outcome prediction to the MiniCog scale. Our frailty evaluation included the following variables: Clinical Frailty Scale (CFS), Lawton's instrumental activities of daily living (IADL), timed to get up and go test (TUGT), grip strength (GS) using a hydraulic hand dynamometer, self-rated health questionnaire (SRH), a question on number of falls in the last year (F), C-reactive protein (CRP) and serum albumin (Alb) levels at the time of the consult. The frailty scale was calculated according to the following formula: 1.5×CFS + 1×IADL +1×GS + 1.5×TUGT +1×SRH+1×F+ 1.5×Alb+2×CRP. The frailty scale score ranged from 0-10.5. With these results we stablished 3 frailty cohorts for the patients being planned for alloHCT, fit (≤1), pre-frail (&amp;lt;1 to ≤5.5), and frail (&amp;gt;5.5), based on this risk model. Results: Median age at transplantation was 59 years and 85 (31%) patients were ≥ 65 years. Of all the patients, 36 (14%) had a Karnofsky Performance Scale Index (KPS) of &amp;lt;90%, 206 patients had a low-intermediate risk disease risk index (DRI). Median time of follow up was 9 months. Majority of the patients (46%) underwent transplantation for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Of all patients, 246 (88.8%) had a normal MiniCog score (&amp;gt;3). There was no difference in 2-y OS between patients with normal and low MiniCog score: 67% (95% confidence interval (CI): 59%-74%) vs 60% (95% CI: 36-78%), p=0.21. NRM at 24 months was 26% (95% CI 10-46%) for patients with an abnormal MiniCog vs 23% (95% CI 17-30%), p=0.80. There was no difference in 2-year RFS between patients with normal and low MiniCog score: 65% (95% CI 57-72%) vs 43.5% (95% CI 23-63%), p=0.09. Using the frailty scale, 144 (56%) patients were considered fit, 30 (12%) pre-frail and 81 (32%) frail. Using our original frailty scale, the 2-y OS among the fit, pre-frail and frail patients was: 78% (95% CI 65%-87%), 64% (95% CI 53%-74%) and 27% (95% CI 5.6%-55.6%) p=0.005. 2-year NRM was 19.2% (95% CI 9-31%), 23% (16-32%), and 41.6% (95% CI 11-70%) for the fit, pre-frail and frail patients respectively, p=0.12. Relapse free survival at 24 months was 72.5% (95% CI 58-83%), 60.5% (95% CI 50-70%), and 29% (95% CI 6-57%), p=0.003. Conclusions: In our cohort the sole presence of cognitive decline, based on the MiniCog assessment failed to be a predictor of outcomes after allogeneic HCT. However, ability of our preciously established frailty scale to predict transplant outcomes in this new cohort of patients further validates the results of our previous findings. The presence of frailty is an independent predictor of adverse outcomes after allogeneic HCT.

Real World Data of Concurrent Arsenic Trioxide and All-Trans Retinoic Acid with Minimal Use of Anthracycline in the Treatment of Acute Promyelocytic Leukemia

▪In the setting of clinical trials, high cure rates have been reported for acute promyelocytic leukemia (APL) with the chemotherapy-free combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) for low-intermediate risk disease, and with the addition of gemtuzumab ozogamicin or minimal anthracycline for high-risk disease. Despite clear in-vitro synergy between ATO and ATRA, most clinical trial protocols in APL have not used these drugs concurrently beyond induction. There is limited real world data on the use of chemotherapy-free combination of ATO and ATRA with minimal anthracycline use in the treatment of APL, especially in the high risk group. We did a retrospective analysis of the clinical outcomes of patients with newly diagnosed APL treated at our center from January 2015 to May 2020 using concurrent ATO, ATRA and minimal anthracycline in a risk stratified manner. The data was frozen and analyzed as on 1st June 2021. During the study period, 167 patients were diagnosed to have APL at our hospital. Of these, we excluded 5 patients who had presented with relapsed disease and 28 patients who were treated with single agent ATO. The remaining 134 patients were treated with a uniform protocol as summarized in Figure 1a. Figure 1b shows the KM plot for EFS (2 year: 90.8±2.5%) for these 134 patients. For analysis of regimen safety and efficacy, we excluded patients who wished to pursue treatment elsewhere within the first 1 week of treatment (n=7), and patients who had severe infections or life-threatening bleeding at presentation or before therapy initiation and subsequently died (n=4). Thus, a total of 123 patients with newly diagnosed APL were included for further analysis. The median age was 35 years (IQR: 24 to 45 years). Forty-six (37.4%) were females. The median duration of symptoms prior to admission was 14 days (IQR: 7 to 28 days). Sixty-one (49.6%) had high risk APL while the remaining 62 (50.4%) had low-intermediate risk APL. During induction, 28 (22.7%) patients had major bleeding while 5 (4%) patients developed major thrombosis. Sixty-seven (55%) patients had at least one documented infection during induction therapy. The median number of packed red cell concentrates, fresh frozen plasma, platelet rich concentrates and cryoprecipitates transfused during induction therapy was 5 (IQR: 3 to 6.5), 10 (IQR: 3 to 30), 40 (IQR: 23 to 55) and 6 (IQR: 0 to 18) respectively. Nineteen (15.4%) patients developed differentiation syndrome; all were treated with steroids, 8 required transient cessation of treatment and 6 required intensive care. Eight (6.5%) patients died during induction. During induction, grade 3 hepatotoxicity was noted in 8 (6.5%) patients, 10 (8.1%) patients had ATRA related headache or benign intracranial hypertension of which 5 required transient cessation of ATRA, while 11 (8.9%) patients had transient QTc prolongation of which 6 required transient cessation of ATO. Seventeen (13.8%) patients developed symptomatic sensory neuropathy requiring treatment. None required permanent discontinuation of therapy. At a median follow up of 854 days, there were 2 (1.6%) hematologic relapses and no deaths beyond induction therapy. The 2-year OS and EFS for the cohort (n=123) are 93.4% ± 2.3% and 91.6% ± 2.6% respectively (Figure 1c). Two (1.6%) patients have developed second malignancies. In a real world setting, concurrently administered ATO and ATRA with minimal anthracycline use results in excellent long term survival, even in the high risk group. Early deaths due to delayed presentation with infections and life threatening bleeding remain an unmet need for future research along with the need for strategies to reduce treatment-related toxicities. [Display omitted] DisclosuresMathews: Christian Medical College: Patents & Royalties: US 2020/0345770 A1 - Pub.Date Nov.5, 2020; AML: Other: Co-Inventor.

Tumor Control Probability Modeling and Systematic Review of the Literature of Stereotactic Body Radiation Therapy for Prostate Cancer

Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group. Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/β = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%. We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning.

A Phase I/II Study of Stereotactic Hypofractionated Once-weekly Radiation Therapy (SHORT) for Prostate Cancer

AimsStereotactic radiation therapy has been investigated predominantly in patients with low–intermediate-risk disease. We conducted a clinical trial of stereotactic hypofractionated radiation therapy delivered in once-weekly fractions on patients with all-risk non-metastatic disease to test feasibility, acute toxicities and patient-reported outcomes. Materials and methodsIn this phase I/II study, 30 patients with prostatic adenocarcinoma, any Gleason score, T1-4N0 and prostate-specific antigen ≤60 ng/ml were treated with volumetric intensity modulated arc radiation therapy to a dose of 35 Gy in five fractions delivered once weekly. Patients with high-risk disease also received elective nodal irradiation to a dose of 25 Gy in five fractions simultaneously. Androgen deprivation was offered to intermediate- and high-risk patients. The primary outcome was acute toxicity. Secondary outcome measures included biochemical control and late toxicity. Patient-reported outcomes were measured using the International Prostate Symptom Score and European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ). ResultsAll 30 patients completed treatment per-protocol. Most patients had T3 (60%) and Gleason 7 (50%) tumours. The median prostate-specific antigen was 17 ng/ml. High-risk disease was present in 20 patients (66.7%). There was a low incidence of acute toxicities (grade 2 + urinary 3.3%, grade 2 rectal 0%). Within the EORTC QLQ framework, only the urinary symptom score showed a clinically meaningful worsening from a mean of 20/100 at baseline to 34/100 at the end of treatment (P < 0.001), but reduced to 24/100 at 6 months (P = 0.08). With a median follow-up of 41.5 months, two patients each reported grade 2 late urinary and rectal toxicity. The 3- and 4-year biochemical control rates were 96.7 and 87.9%, respectively. ConclusionIn a cohort of mainly high-risk cancers, stereotactic once-weekly radiation therapy was easy to implement and well tolerated, with a low incidence of acute and late toxicity and excellent biochemical control.

Perioperative Intravesical Chemotherapy for Patients WithNon–Muscle-invasive Bladder Cancer: Understanding the Extent of and Sources of Variation in Guideline-recommended Use

ObjectiveTo examine intravesical chemotherapy (IVC) use according to non–muscle-invasive bladder cancer patient disease risk, and the contributions of multilevel factors to variation in proficient use among patients with low-intermediate disease. MethodsThis study included 988 patients diagnosed with non–muscle-invasive bladder cancer in an integrated health system in Northern California from 2015-2017. We calculated IVC receipt by disease risk, and among patients with low-intermediate risk disease, assessed the relationship between multilevel factors and IVC receipt using a logistic regression model with random intercepts for provider and service area, and patient-, provider-, and service area-level fixed effects. We further assessed the association of provider- and service area-level factors with IVC use by examining intraclass correlation coefficients. ResultsSimilar proportions of low-intermediate (36%) and high-risk (34%) patients received IVC. In the multivariate analysis, including low-intermediate risk patients, service area volume was strongly and statistically significantly associated with IVC use (adjusted odds ratio, high- vs low-volume: 0.08, 95% Confidence Interval: 0.01-0.58). Provider- and service area-level intraclass correlation coefficients were large, (38%, P = .0009 and 39% P = .03, respectively) indicating that much of the variance in IVC use was explained by factors at these levels. ConclusionOur findings highlight opportunities to improve proficient use of IVC. Future research should assess provider- and practice-level barriers to IVC use among low-intermediate risk patients.

MP12-07 TARGETED BIOPSIES IN MEN ON ACTIVE SURVEILLANCE FOR LOW-RISK PROSTATE CANCER: WHEN IS UPGRADING REALLY INCREASED RISK?

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I1 Apr 2018MP12-07 TARGETED BIOPSIES IN MEN ON ACTIVE SURVEILLANCE FOR LOW-RISK PROSTATE CANCER: WHEN IS UPGRADING REALLY INCREASED RISK? Daniël Osses, Jan Verbeek, Frank-Jan Drost, Monique Roobol, and Ivo Schoots Daniël OssesDaniël Osses More articles by this author , Jan VerbeekJan Verbeek More articles by this author , Frank-Jan DrostFrank-Jan Drost More articles by this author , Monique RoobolMonique Roobol More articles by this author , and Ivo SchootsIvo Schoots More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.394AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To reduce undergrading magnetic resonance imaging (MRI) and targeted biopsies (TBx) are increasingly used in men on active surveillance (AS) for low-risk prostate cancer (PCa). However, risk thresholds are not yet fully understood when MRI ± TBx strategy is used during AS. Its use could namely result in ′risk inflation′ where a PCa that is stable may be more accurately sampled at TBx and found to include higher risk features than when it would be sampled in a systematic way. We present the number of men on AS who upgrade to Gleason score (GS) 3+4, 4+3 and ≥4+4 PCa based on MRI ± TBx. METHODS Men on AS received an MRI at baseline (3 months after diagnosis), at confirmatory (first repeat) biopsy or at surveillance biopsy. If indicated (PI-RADS suspicion score ≥3) men underwent TBx using MRI-TRUS fusion. Biopsy outcomes were categorized to any PCa, GS 3+4, GS 4+3 and GS ≥4+4 PCa based on MRI ± TBx on a per-patient and on a per-lesion basis. RESULTS Between 2014 and 2017 our prospective clinical database consists of 331 men on AS with GS 3+3 PCa (median age 67 yr, interquartile range [IQR] 62-72; median PSA level 8.0 ng/ml, IQR 5.6-12). 198 men had a suspicious lesion (PI-RADS ≥3) on MRI (Table 1A). MRI ± TBx detected any PCa in 51% of all men and in 169/198 (85%) of men with a suspicious lesion. One out of four of all men showed GS upgrading (≥3+4); a positive MRI showed in 82/198 (41%) men GS upgrading, only 24/198 (12%) showed upgrading to GS ≥4+3 PCa. Any PCa was detected in 213/265 suspicious lesions (80%) in 198 men on AS (Table 1B). A total of 95/265 (36%) suspicious lesions showed GS upgrading; only 25/265 (9%) lesions showed upgrading to GS ≥4+3 PCa. The per-patient and per-lesion analyses showed similar results. Additional analysis at any time point of the MRI within the AS work-up did not result in significant differences between upgrading. CONCLUSIONS Based on a suspicious MRI and subsequently TBx 41% of men on AS showed upgrading from GS 3+3 to ≥3+4 PCa. The majority of these men was classified into low intermediate-risk disease (GS 3+4); it might be wrong to falsely encourage men to cease AS because of an apparent increase in risk (reclassification) rather than a true change in their cancer. Only 12% of men on AS showed upgrading to GS ≥4+3 PCa. These men may have a worse prognosis. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e137 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Daniël Osses More articles by this author Jan Verbeek More articles by this author Frank-Jan Drost More articles by this author Monique Roobol More articles by this author Ivo Schoots More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Phase 1/2 Study on Stereotactic Hypofractionated Once-Weekly Radiation Therapy for Nonmetastatic Prostate Cancer

Stereotactic radiotherapy has shown promising results in Phase II studies, but has been investigated predominantly in patients with low-intermediate risk disease. We conducted a clinical trial of stereotactic hypofractionated radiotherapy delivered in once-weekly fractions on patients with non-metastatic disease to test feasibility, acute toxicities, patient reported outcomes, and biochemical control in a cohort with predominantly high-risk disease. Patients with prostatic adenocarcinoma, Gleason 6-10, T1-4N0 (staged with multiparametric MRI and bone scans) and PSA <=60 ng/ml were eligible for enrolment into this Phase I/II trial. A planned sample of 30 patients were treated with volumetric intensity modulated arc radiation therapy to a dose of 35 Gy in 5 fractions delivered once-weekly with an overall treatment time of 29 days. Patients with high-risk disease also received elective nodal irradiation to a dose of 25 Gy in 5 fractions simultaneously. Androgen deprivation was offered to intermediate and high risk patients. Trial specific dose constraints were ensured. The primary outcome was acute toxicity with NCI CTC v4. Secondary outcome measures included biochemical control and late toxicity. Patient reported outcomes were measured with the IPSS score and EORTC QLQ-C30 and PR25 questionnaires. Clinically meaningful worsening of quality of life scores was defined as a 10 point reduction (out of 100) in any scale. All 30 patients completed treatment per-protocol. The majority of patients had T3 (60%) and Gleason 7 (50%) tumors. The median PSA was 17 ng/ml. High risk disease was present in 20 patients (66.7%). There was low incidence of acute toxicities (Grade 2+ urinary toxicities in 1 -3.3%, and grade 2+ rectal toxicities in none). The mean IPSS scores increased from baseline 8.6 to 14.6 at the end of treatment (P < 0.001) but reduced to 10.9 at 6 months (P = 0.05). Of the 21 parameters studied in the EORTC QLQ framework, only the urinary symptom score showed a clinically meaningful worsening from a mean of 20/100 at baseline to 34/100 at end of treatment (P < 0.001), but reduced to 24/100 at 6 months (P = 0.08). Other functional or symptomatic scales did not show any clinically meaningful worsening. There was 1 patient each with late grade 2 rectal bleeding and grade 2 urinary toxicity. With a median follow-up of 25 months, 1 patient developed a distant failure at 10 months, with a 2 year biochemical control rate of 96.7%. In a cohort of mainly high risk cancers in a developing country, stereotactic once-weekly radiation therapy was easy to implement, safe and well tolerated with a low incidence of acute toxicity. Preliminary biochemical control and late toxicity profiles are encouraging. This paves the way for further prospective evaluation in a larger cohort of patients with high-risk disease.

Phase I/II study on stereotactic hypofractionated once-weekly radiation therapy (SHORT) for localized prostate cancer.

130 Background: The low α/β ratio of prostate cancer (PrCa) is well established. However, stereotactic hypofractionated radiotherapy (SRT) has been investigated primarily in highly selected patient populations with low-intermediate risk disease. We performed a clinical trial of SRT delivered in once-weekly fractions on an unselected cohort of patients with non-metastatic PrCa. Methods: In this Phase I/II study 30 patients with non-metastatic PrCa (multiparametric MRI cT1-4N0, M0, Gleason 6-10, PSA &lt; = 60 ng/ml) were treated with SRT to a prescription dose of 35Gy in 5 fractions delivered once a week (overall treatment time 29 days). Elective nodal RT at 25Gy/5Fr was delivered in patients high-risk by NCCN criteria, and androgen deprivation therapy given to intermediate and high-risk patients. SRT was planned using volumetric intensity modulated arc therapy (VMAT) or Helical Tomotherapy (HT) with pre-defined dose-criteria. The primary endpoint was acute toxicity NCI CTC v4, and secondary endpoints were biochemical control and late toxicity. Results: Thirty patients completed treatment per-protocol. Stage T3, Gleason 8-10, and PSA &gt; 10 was seen in 18 (60%), 7 (23%) and 24 (80%) respectively. Overall 20 (66.7%) were high-risk. Median of Mean PTV dose was 36Gy, and normal tissue constraints could be met in all patients (Table). Acute urinary toxicities (Gr 0: 1; Gr 1: 27; Gr 2: 1; Gr 3-4: 0) and acute rectal toxicities (Gr 0: 20; Gr 1: 10; Gr 2: 0; Gr 3-4: 0) were very modest. The mean IPSS scores at baseline, end of treatment and 3 months after treatment were 8.8, 14.7, and 9.9. With a median follow up of 23.7 months, the 2 year biochemical control was 96%. Late grade 2 rectal bleeding developed in 1 patient. Conclusions: Carefully planned stereotactic VMAT/HT based once-weekly SRT to a predominantly high-risk non-metastatic PrCa cohort was very well tolerated and found to be safe for clinical use. Preliminary biochemical control and late toxicity profiles are encouraging. Clinical trial information: CTRI/2016/02/006671. [Table: see text]

Clinical Factors Predicting Tumour Upgrading in Patients Under Active Surveillance and Elected to Active Treatment after Disease Reclassification or Progression

Objectives: To evaluate clinical factors associated with tumour upgrading (UPG) in low-intermediate risk patients who progressed while under active surveillance (AS) and underwent delayed radical prostatectomy. Material and Methods: The evaluated factors included prostate specific antigen (PSA), prostate volume, PSA density and number of biopsy positive cores (BPC). Multivariate logistic regression by the forward step Wald procedure was used. Results: The study evaluated 24 patients who had UPG in 13 cases (54.2%). Independent factors associated with tumour UPG included PSA (OR 2.1; p = 0.047) and BPC (OR 2; p = 0.042). Conclusions: Clinical factors associated with UPG were identified in patients who were under AS for with low-intermediate risk disease. Preoperative PSA levels and number of BPC were independent factors associated with UPG in a contemporary cohort of patients who progressed under AS and underwent delayed active treatment.

The impact of body mass index on treatment outcomes for patients with low-intermediate risk prostate cancer.

BackgroundLittle is known about the relationship between preoperative body mass index and need for adjuvant radiation therapy (RT) following radical prostatectomy. The goal of this study was to evaluate the utility of body mass index in predicting adverse clinical outcomes which require adjuvant RT among men with organ-confined prostate cancer (PCa).MethodsWe used a prospective cohort of 1,170 low-intermediate PCa risk men who underwent radical prostatectomy and evaluated the effect of body mass index on adverse pathologic features and freedom from biochemical failure (FFbF). Clinical and pathologic variables were compared across the body mass index groups using an analysis of variance model for continuous variables or χ2 for categorical variables. Factors related to adverse pathologic features were examined using logistic regression models. Time to biochemical recurrence was compared across the groups using a log-rank survivorship analysis. Multivariable analysis predicting biochemical recurrence was conducted with a Cox proportional hazards model.ResultsPatients with elevated body mass index (defined as body mass index ≥25 kg/m2) had greater extraprostatic extension (p = 0.004), and positive surgical margins (p = 0.01). Elevated body mass index did not correlate with preoperative risk groupings (p = 0.94). However, when compared with non-obese patients (body mass index <30 kg/m2), obese patients (body mass index ≥30 kg/m2) were much more likely to have higher rate of adverse pathologic features (p = 0.006). In patients with low- and intermediate- risk disease, obesity was strongly associated with rate of pathologic upgrading of tumors (p = 0.01 and p = 0.02), respectively. After controlling for known preoperative risk factors, body mass index was independently associated with ≥2 adverse pathologic features (p = 0.002), an indicator for adjuvant RT as well as FFbF (p = 0.001).ConclusionsBody mass index of ≥30 kg/m2 is independently associated with adverse pathologic features, which is an indicator for additional RT, particularly in patients with low-intermediate risk disease. Future studies may determine if this select group of patients may be best treated with definitive RT to reduce toxicity from additional RT following radical prostatectomy. We propose including body mass index in clinical decision-making for appropriate treatment recommendation for patients with low-intermediate risk PCa.

Managing Endometrial Cancer: The Role of Pelvic Lymphadenectomy and Secondary Surgery.

In November 2010, the French National Cancer Institute published new guidelines for managing endometrial cancer. Pelvic lymphadenectomy is not indicated for preoperative low-intermediate risk type 1 endometrial cancer, and high-risk patients should undergo secondary surgery with para-aortic lymphadenectomy. This study evaluated these new guidelines with regard to overall survival (OS), relapse-free survival (RFS), and morbidity for patients with low-intermediate risk disease. We evaluated all type 1 endometrial cancer patients with low-intermediate risk of recurrence who were treated from 1 January 1997 through 31 December 2012. All patients were classified according to the 2009 International Federation of Gynecology and Obstetrics staging criteria and the European Society for Medical Oncology. Overall, 230 patients were included (159 before and 71 after the new guidelines were issued). Pelvic lymphadenectomies were performed before and after the new guidelines in 77.4 and 28.6 % of patients, respectively (p < 0.001). After 2010, eight patients also underwent secondary surgery, which consisted of a para-aortic lymphadenectomy for lymphovascular space invasion (LVSI). This second surgery changed the adjuvant treatment for one patient. OS and RFS were similar between both groups, and no difference in morbidity was observed between the groups. LVSI was an independent factor for OS [hazard ratio (HR) 7.2, 95 % CI 3.1-17; p < 0.001] and RFS (HR 3.7, 95 % CI 1.6-8.5; p < 0.003). Fewer pelvic lymphadenectomies in low-intermediate risk patients did not affect OS, RFS, or morbidity, including patients with secondary surgery. We must gather additional data with a longer follow-up period to not only confirm our results but to also fully investigate the paradoxical absence of decreased morbidity that our study has shown.

Conditioning Intensity In Middle Aged Patients With AML In CR1. No Advantage For Myeloablative Regimens Irrespective Of The Risk Group. An Observational Analysis By The Acute Leukemia Working Party Of The EBMT

IntroductionIn younger patients with AML achieving CR1 with intermediate or high risk disease allogeneic HSCT is the treatment of choice. Conditioning intensity is varied, reduced intensity (RIC) conditioning regimens are usually given to older patients, whereas young patients traditionally receive myeloablative regimens (MAC). In patients between the ages of 40-60 both types of regimens are used with little knowledge about factors that would lead physicians to prefer one over the other. Previous studies had shown that RIC regimens were associated with somewhat higher relapse risks but lower risks of transplant related mortality (TRM). We hypothesized that in low-intermediate risk disease based on cytogenetic classification RIC is superior to MAC whereas in high risk leukemia MAC is superior to RIC given higher antileukemic activity. Patients and MethodsThis study included 2974 of 5388 eligible patients with AML transplanted in CR1 in 2000-2011 based on the availability of cytogenetics to classify by risk status at diagnosis. Only sibling or unrelated donors and marrow or peripheral blood stem cell transplants were considered. Regimens were classified as MAC (n=1638) or RIC (n=1336) based on published criteria. Median follow-up of surviving patients was 46 and 41 months respectively. Groups differed by many variables. MAC recipients were significantly younger (37.6 vs 53.8 years), had a shorter interval from diagnosis to transplantation (143 vs 165 days), were more frequently male (53% vs 48%), had less frequently poor risk cytogenetics 19% vs 22%, received less frequently stem cells from an unrelated donor (20% vs 33%), and had more frequently marrow as a stem cell source (36% vs 7%). The Kaplan-Meier estimator, the cumulative incidence function and Cox proportional hazards regression models were used where appropriate. ResultsTable 1 shows similar overall (OS) and leukemia free survival (LFS) in both groups but a lower relapse incidence (RI) and a higher transplant related mortality incidence (TRM) in the MAC group. Acute grade II-IV GvHD was higher with MAC, incidence of chronic GvHD did not differ significantly.Table 13y OS3y LFS3y RI3y TRM100d II-IV aGVHD3y cGVHDMAC57±1%53±1%22±1%23±1%32±1%46±1%RIC58±1%52±1%33±1%14±1%22±1%49±1%0.540.31<0,0001<0,0001<0,00010.13In univariate analysis overall survival was higher with RIC in cytogenetic good risk AML (55±5% vs 77±7% MAC vs RIC) but not in intermediate risk (61±1% vs 62±2%) or poor risk AML (42±3% vs 40±3%). Relapse incidence was lower with MAC in poor risk AML (36±3% vs 51±3%) and intermediate risk AML (21±1% vs 30±1%) but not in good risk AML (19±4% vs 13±5%). TRM was higher in MAC vs RIC in all three cytogenetic risk groups. Multivariate analysis confirmed a significant LFS and OS advantage of RIC in good risk but not in intermediate and poor risk leukemia. ConclusionsIn patients aged 40-60 MAC conditioning has no advantage over RIC conditioning in spite of RIC transplant recipients being generally in a poorer risk category. We confirm lower relapse rates but higher TRM risks with MAC compared to RIC. We fail to show superiority of MAC in patients with high risk cytogenetics but there appears to be an advantage for RIC over MAC in the small cohort of patients with good risk leukemia. Disclosures:Kuball:Miltenyi: GMP product development Other.

External radiotherapy versus vaginal brachytherapy for patients with intermediate risk endometrial cancer

Purpose To determine if brachytherapy alone is adequate adjuvant local therapy in patients classified as intermediate risk after complete surgical staging for endometrioid adenocarcinoma. Methods Between 1991 and 2004, 78 patients with FIGO stage IA–II (occult) disease meeting the eligibility criteria of GOG 99 received adjuvant radiotherapy following complete surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy, peritoneal cytology, and pelvic ± para-aortic lymphadenectomy) for endometrioid adenocarcinoma at Washington University in St. Louis. Forty-two patients received postoperative vaginal brachytherapy alone and 36 received postoperative pelvis external radiotherapy (XRT) and vaginal brachytherapy. Fifty-two patients were classified as having high intermediate risk disease and 26 patients had low intermediate risk disease as defined by GOG 99. Median follow-up for all patients was 55 months. Results The 5-year overall and disease-free survivals for all patients were 86% and 89%, respectively. There was no difference in 5-year disease-free survivals among patients classified as high intermediate risk vs. low intermediate risk ( p = 0.26) or in terms of radiation treatment received ( p = 0.95). There were two patients that had > grade 2 gastrointestinal complications, both were treated with external radiotherapy and vaginal brachytherapy. Conclusions Vaginal brachytherapy alone results in minimal morbidity and is adequate local therapy for intermediate risk patients with endometrioid adenocarcinoma after complete surgical staging.