Primary External Beam Radiotherapy Research Articles

Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.

The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy. We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM). Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages. In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.

Optimizing External Beam Radiotherapy as per the Risk Group of Localized Prostate Cancer: A Nationwide Multi-Institutional Study (KROG 18-15).

Simple SummaryThis multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer to identify the optimal EBRT strategy for each risk-stratified patient subgroup for clinical practice implementation. In 1573 patients from 17 institutions, EBRT treated prostate cancer effectively. Also, among various risk classification tools, NCCN classification revealed the highest predictive power. The modern RT techniques and dose escalation (≥179 Gy1.5) enhanced therapeutic effects of RT significantly, especially in the high-risk group. On the other hand, modest doses (≥170 Gy1.5) was a significant factor in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. IMRT+ ≥179 Gy1.5+ hypofractionation resulted in higher biochemical failure-free survival in all risk groups, and it translated into survival benefits in the high-risk group. Therefore, risk-adapted RT (more intense RT, high-risk patients; moderate-dose RT, low-risk patients) can be considered, although further prospective studies are warranted.Purpose: This nationwide multi-institutional study analyzed the patterns of care and outcomes of external beam radiotherapy (EBRT) in localized prostate cancer patients. We compared various risk classification tools and assessed the need for refinements in current radiotherapy (RT) schemes. Methods and Materials: We included non-metastatic prostate cancer patients treated with primary EBRT from 2001 to 2015 in this study. Data of 1573 patients from 17 institutions were analyzed and re-grouped using a risk stratification tool with the highest predictive power for biochemical failure-free survival (BCFFS). We evaluated BCFFS, overall survival (OS), and toxicity rates. Results: With a median follow-up of 75 months, 5- and 10-year BCFFS rates were 82% and 60%, and 5- and 10-year OS rates were 95% and 83%, respectively. NCCN risk classification revealed the highest predictive power (AUC = 0.556, 95% CI 0.524–0.588; p < 0.001). Gleason score, iPSA < 12 ng/mL, intensity-modulated RT (IMRT), and ≥179 Gy1.5 (EQD2, 77 Gy) were independently significant for BCFFS (all p < 0.05). IMRT and ≥179 Gy1.5 were significant factors in the high-risk group, whereas ≥170 Gy1.5 (EQD2, 72 Gy) was significant in the intermediate-risk group and no significant impact of dose was observed in the low-risk group. Both BCFFS and OS improved significantly when ≥179 Gy1.5 was delivered using IMRT and hypofractionation in the high-risk group without increasing toxicities. Conclusions: With NCCN risk classification, dose escalation with modern high-precision techniques might increase survivals in the high-risk group, but not in the low-risk group, although mature results of prospective studies are awaited.

Early Experience with Salvage Retzius-sparing Robotic-assisted Radical Prostatectomy: Oncologic and Functional Outcomes

ObjectiveTo report on feasibility, safety, and continence outcomes using the Retzius-sparing approach in the salvage setting (sRS-RARP). Materials and MethodsA total of 26 patients underwent robotic salvage prostatectomy at our institution from January 2012 to May 2020 by a single surgeon (RM). Twenty patients underwent sRS-RARP and 6 underwent the standard approach (sRARP). Pre-, intra-, and postoperative outcomes were compared between these groups with emphasis on continence and oncologic safety. ResultsPatients had comparable preoperative characteristics with no significant difference in age, race, prostate-specific antigen level, and Gleason score. Most patients underwent primary external beam radiation therapy (69.2%). Median time to biochemical failure was 7.9 years (IQR 6.1-13.4). sRS-RARP required less console time (141.5 vs 199.5.0 minutes, P = .008) and less blood loss (50.0 mL vs 100.0 mL, P = .045) compared to sRARP. Postoperative course was uneventful with a median hospital stay of 1 day. Median catheterization time was 14.0 days (IQR 11.5-17). Patients undergoing sRS-RARP had better immediate (25.0% vs 0.0%, P < .001), 3 month (80.0% vs 0%, P < .001), and 12 month continence rates (100% vs 44%, P = .0384) compared to sRARP patients. Likewise, median time to continence was significantly shorter for sRS-RARP patients (90.0 vs 270.0 days, P = .0095). Biochemical recurrence rate was 20.0% in the sRS-RARP group and 33.3% in the sRARP group (P = .60). ConclusionEarly experience suggests that sRS-RARP is feasible, oncologically safe, and may offer improved continence compared to the sRARP approach.

Systemic Inflammatory Markers Can Predictive Response in Radiation Therapy to the Prostate

The neutrophil/lymphocyte ratio (NLR) is an independent predictor of recurrence in several cancers and is a well-established prognostic factor for prostate cancer (PCa). In a meta-analysis, NLR was found to be associated with a lower rate of overall survival and recurrence-free survival. We aim to identify a subgroup of patients with PCa who have different recurrence rate based on NLR. From our institutional database, we identified 628 patients who had primary external beam radiotherapy or permanent seed brachytherapy from April 2005 to August 2019. All patients had to have a complete blood count within 3 months before the start of treatment. Patients without a recurrence were included if they had a follow-up of at least 24 months. Only patients with CAPRA low (score 0-2) and intermediate–risk (3-5) cancers were included. No patient received either androgen deprivation or brachytherapy as a boost. Biochemical recurrence (BCR) was defined according to the Phoenix definition (nadir +2). Log-rank test was used in univariate analysis (UVA) and Cox regression analysis in multivariate analysis (MVA) to predict for BCR. Median follow-up without recurrence was 60 months (IQR 44-48months), 30 patients had a recurrence. An NLR >3 was more frequent in diabetics (p = 0.042) and in statin users (p = 0.014). On UVA, an NLR >3 was associated with less BCR (p = 0.029) while CAPRA low- vs. intermediate risk was not (p = 0.055). Additionally, on MVA, an NLR >3 was associated with less BCR (HR 0.37, 95% CI 0.15-0.90, p = 0.029). CAPRA intermediate risk patients with an NLR <3 (n = 157) had the worst (p = 0.009) BCR rates when compared to all other patients (n = 471). We were able to identify a subgroup of patients with CAPRA intermediate-risk PCa and an NLR<3 who had worse BCR. This is in contrast to most other cancers who have a worse prognosis when the NLR is high. Contrary to other cancers, prostate radiotherapy in low- and intermediate-risk cancers seems to benefit from a higher neutrophil ratio in peripheral blood.

Radical External-Beam Radiotherapy in Combination With Intracavitary Brachytherapy for Localized Carcinoma of the Cervix in Sri Lanka: Is Treatment Delayed Treatment Denied?

PURPOSERadical external-beam radiotherapy (EBRT) followed by intracavitary brachytherapy is standard of care for patients with localized carcinoma of the cervix unsuitable for radical surgery. However, outcome data are scarce in resource-limited settings. We conducted a retrospective analysis of survival in a cohort of patients treated with this strategy in Sri Lanka.PATIENTS AND METHODSAll patients with localized cervical cancer treated with primary EBRT and intracavitary brachytherapy from 2014 to 2015 were included in the study. Primary end point was disease-free survival (DFS), defined as time to local or systemic recurrence or death. Univariable analysis was performed to determine the prognostic significance of the following variables: age, stage, use of concurrent chemotherapy, EBRT dose, brachytherapy dose, and time to completion of treatment (dichotomized at 60 days). Factors significant on univariable analysis were included in a multivariable model.RESULTSA total of 113 patients with available data were included in the analysis. Mean age was 58 years (range, 35-85 years), and most patients (n = 103 of 113) presented with stage ≥ IIB disease. Median time to delivery of brachytherapy from commencement of EBRT was 110 days (range, 34-215 days), with only 12 (11%) of 113 patients completing treatment within 60 days. Median follow-up was 28 months (range, 5-60 months), and 2-year DFS was 63.7% (95% CI, 55.4% to 73.2%). Treatment delay was the only significant factor associated with inferior DFS on univariable analysis (log-rank P = .03), and therefore, multivariable analysis was not performed.CONCLUSIONThere are significant delays in receiving intracavitary brachytherapy after completing EBRT for cervical cancer in Sri Lanka, which is associated with inferior DFS. Increasing brachytherapy resources is an urgent priority to improve outcomes of patients with cervical cancer.

Partial prostate re-irradiation for the treatment of isolated local recurrence of prostate cancer in patients previously treated with primary external beam radiotherapy: short-term results of a monocentric study.

Many different therapeutic options are available for locally recurrent prostate cancer (PCa). However, standard treatment has not yet been established. We conducted a partial prostate re-irradiation (PPR) program for the treatment of isolated and limited-size intraprostatic recurrences, in patients who previously underwent external beam radiation therapy (EBRT) as primary treatment for prostatic cancer (PCa). The analysis of this experience in terms of feasibility, toxicity, and efficacy is reported. The inclusion criteria of this retrospective analysis were: previous definitive EBRT, evidence of biochemical recurrence, radiological detection of isolated local relapse, and PPR as local salvage therapy. Gastrointestinal (GI) and genitourinary (GU) toxicities were registered according to the RTOG/EORTC criteria. Between July 2012 and May 2019, 44 patients were treated with PPR. All patients completed the planned treatment. The median follow-up was 25.4 months. Tumor progression was observed in 18 patients (40.9%). Two-year local control, biochemical failure-, and clinical relapse-free survival rates were 90.1%, 58.3%, and 67.9%, respectively. The occurrence of biochemical failure after PPR is lower for patients with the time interval between the primary EBRT and first biochemical failure >4 years; local control results strongly associated with a biologically effective dose (BED) at first EBRT >177 Gy. No acute grade 3 or greater toxic events were observed. Two late grade 3 GU toxicities were reported. Although retrospective in design, our study indicates that PPR appears as a feasible, well-tolerated, and effective salvage treatment for isolated local PCa recurrence. Long term data are required in order to confirm these results.

Negative 11C-choline PET/computed tomography imaging in restaging of patients with prostate cancer with serum prostate-specific antigen values >20 ng/mL.

Several studies have reported about the performance of C-choline-PET/computed tomography (CT) (choline) in patients with biochemical recurrent (BCR) prostate cancer, but there is a lack of information regarding negative choline in the same clinical setting. Our aim was to retrospectively analyse negative choline in a cohort of BCR-patients with high prostate-specific antigen (PSA). We retrospectively analysed all choline-scans performed at two high-volume imaging centres between 2005 and 2018, selecting those of interest according to the following inclusion criteria: (1) proven prostate cancer treated either with radical prostatectomy or primary external beam radiation therapy (EBRT), (2) BCR after radical prostatectomy or EBRT, (3) PSA serum values >20 ng/mL at the time of scan and (4) scan reported as negative for active disease. Overall, among 5792 scans performed for BCR-prostate cancer, 14 matched the inclusion criteria and were classified as follows: 5/14(36%) inaccurate reports, 3/14(21%) questionable underestimation of positive findings, originally described as unclear, 6/14(43%) negatives. Choline showed a high detection rate in BCR-prostate cancer patients with PSA >20 ng/mL. Although negative reports can be found in this clinical setting, in our review various disease-relevant findings were identified in more than half of the cases originally reported as negative warranting a double reading in such cases to avoid false-negative reports.

Active surveillance before radiotherapy: Outcome and predictive factors for multiple biopsies before treatment.

We aimed to investigate whether patients on active surveillance (AS) had worse outcomes than patients who received immediate treatment with radiotherapy and whether a Gleason grade progression on repeat biopsy influenced outcome. From our institutional database, we identified 2001 patients treated between 2005 and 2019 with primary external beam radiation therapy or brachytherapy. Biochemical recurrence (BCR) was analyzed in relation to clinical factors such as a Gleason grade progression or having multiple biopsies vs. only one biopsy. Patients on AS were identified as those who had undergone ≥2 biopsies. We used log-rank tests for univariate analysis (UVA) and Cox regression analysis for multivariable analysis (MVA). Of 2001 patients, 374 (19%) patients had ≥2 biopsies before treatment, of which 48% presented with a Gleason grade progression of mostly to Gleason 3+4 (36%); 32% had a cancer volume increase on biopsy and 16% had no significant change on biopsy. For patients with ≥2 biopsies, median time from first biopsy to treatment was 22.0 months (interquartile range [IQR] 14.7-36.1). By UVA, patients with Gleason grade progression (n=105) had a worse BCR-free rate (p=0.02) than patients who had no grade progression on repeat biopsy or only one biopsy. On MVA, this effect was lost. Having ≥2 biopsies was not a significant negative prognostic factor on UVA (p=0.2) or MVA. In our experience, radiotherapy after a period of AS, even with Gleason grade progression, did not lead to worse outcomes compared to patients who had radiotherapy after only one biopsy.

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

MP70-13 COMPARATIVE STUDY BETWEEN SALVAGE CRYOABLATION OF THE PROSTATE AFTER PRIMARY RADIOTHERAPY FAILURE AND AFTER PRIMARY CRYOTHERAPY FAILURE FOR CLINICALLY LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy II (MP70)1 Apr 2020MP70-13 COMPARATIVE STUDY BETWEEN SALVAGE CRYOABLATION OF THE PROSTATE AFTER PRIMARY RADIOTHERAPY FAILURE AND AFTER PRIMARY CRYOTHERAPY FAILURE FOR CLINICALLY LOCALIZED PROSTATE CANCER Hazem Orabi*, Leah Davis, Yuan Wu, and Thomas Polascik Hazem Orabi*Hazem Orabi* More articles by this author , Leah DavisLeah Davis More articles by this author , Yuan WuYuan Wu More articles by this author , and Thomas PolascikThomas Polascik More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000950.013AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Salvage cryoablative therapy for biopsy-proven recurrence after primary radiation or ablation treatment failure for clinically localized prostate cancer (PCa) is common. In this observational study, we aim to explore biochemical recurrence-free survival when salvage cryotherapy is performed after primary cryotherapy failure versus primary external beam radiotherapy failure in patients initially presenting with clinically localized prostate cancer. METHODS: After IRB approval, data for patients treated with salvage cryotherapy after primary external beam radiotherapy (group A) or after primary cryotherapy (group B) were collected from The Duke Prostate Cancer database and the Cryo On-Line Data (COLD) registry. Biochemical recurrence (BCR), using Phoenix criteria, after 2 and 5 years were the primary oncological outcomes. Urinary incontinence, erectile dysfunction, fistula and retention were considered as secondary functional outcomes and were assessed 12 months after salvage cryotherapy. We estimated the association between treatment and biochemical progression-free survival (BPFS) using inverse probability weighted (IPTW) Cox proportional hazards regression. Propensity score analysis, adjusting for Gleason, risk, and PSA, was implemented to account for non-random assignment of primary treatment. To test for differences in the secondary functional outcomes between treatment modalities we used Pearson's χ2 test or Fishers exact test, corrected for IPTW. RESULTS: A total of 515 unweighted subjects met inclusion criteria and had complete data for the primary analysis.Those in group B showed an increase in 2-year BCR (HR 1.94; 95% CI, 1.1–1.34) when compared to group A. The same association was seen in 5-year BCR (HR: 1.66; 95% CI,1.01-2.72).There was no statistical difference between the 2 groups regarding the functional outcomes, although incontinence and erectile dysfunction was higher group A than group B. CONCLUSIONS: Risk of biochemical recurrence for salvage cryotherapy after primary cryoablation is higher than following primary external beam radiotherapy. This should be taken in consideration when selecting primary in-situ therapy for PCa. Further work with larger number of patients is needed to assess reasons for failure including whether they are in field or out of field of treatment. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1060-e1060 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hazem Orabi* More articles by this author Leah Davis More articles by this author Yuan Wu More articles by this author Thomas Polascik More articles by this author Expand All Advertisement PDF downloadLoading ...

MP53-03 ASSESSING RACIAL DISPARITIES IN LOW AND FAVORABLE INTERMEDIATE RISK PROSTATE CANCER PATIENTS OVER A 27-YEAR PERIOD TREATED WITH EXTERNAL BEAM RADIATION THERAPY IN A RACIALLY DIVERSE, EQUAL ACCESS MILITARY HEALTHCARE SYSTEM

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (MP53)1 Apr 2020MP53-03 ASSESSING RACIAL DISPARITIES IN LOW AND FAVORABLE INTERMEDIATE RISK PROSTATE CANCER PATIENTS OVER A 27-YEAR PERIOD TREATED WITH EXTERNAL BEAM RADIATION THERAPY IN A RACIALLY DIVERSE, EQUAL ACCESS MILITARY HEALTHCARE SYSTEM Sean Stroup*, Audry Robertson, Kayla Onofaro, Michael Santomauro, Nicholas Rocco, Huai-ching Kuo, Avinash Chaurasia, Inger Rosner, Timothy Brand, John Musser, Christopher Porter, Grace Lu-Yao, Anthony D'Amico, and Jennifer Cullen Sean Stroup*Sean Stroup* More articles by this author , Audry RobertsonAudry Robertson More articles by this author , Kayla OnofaroKayla Onofaro More articles by this author , Michael SantomauroMichael Santomauro More articles by this author , Nicholas RoccoNicholas Rocco More articles by this author , Huai-ching KuoHuai-ching Kuo More articles by this author , Avinash ChaurasiaAvinash Chaurasia More articles by this author , Inger RosnerInger Rosner More articles by this author , Timothy BrandTimothy Brand More articles by this author , John MusserJohn Musser More articles by this author , Christopher PorterChristopher Porter More articles by this author , Grace Lu-YaoGrace Lu-Yao More articles by this author , Anthony D'AmicoAnthony D'Amico More articles by this author , and Jennifer CullenJennifer Cullen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000915.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Racial disparities in prostate cancer health outcomes, especially among African American men, continue to be a significant national concern. We evaluated longitudinal cancer-related outcomes in the context of racial disparities for patients with low and favorable-intermediate risk PCa treated with primary external beam radiotherapy (EBRT). METHODS: Patients consented and enrolled into the Center for Prostate Disease Research Multicenter National Database and diagnosed with low and favorable-intermediate PCa between 1990 and 2017 and treated with EBRT were eligible. Clinical and pathologic factors were compared between African American (AA) and Caucasian American (CA) men. Biochemical recurrence (BCR)-free, distant metastasis (DM)-free, and overall survival probability estimates were computed using Unadjusted Kaplan-Meier (KM) estimation curve analysis and multivariable Cox proportional hazards (PH) analysis, controlling for key study covariates.KM curves were also used to analyze prostate specific antigen (PSA) doubling time (PSADT) within each racial group for those that developed DM. RESULTS: Of the 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. Median age at time of EBRT was significantly different between racial groups with AA men being treated at a younger age. AA men were more likely to have a higher biopsy-detected Gleason Score compared to CA men. Unadjusted KM estimation curves demonstrated no differences between races when looking at probability of BCR-free, DM-free, and overall survival over time. Multivariable Cox PH analyses revealed no significant differences between AA and CA men when assessing survival time from radiation therapy (RT) to BCR (AHR=1.2, 95% CI=0.6-2.7, P=0.586), RT to DM (AHR=2.3, 95% CI=0.6-9, P=0.242) and RT to overall death (AHR=1.3, 95% CI=0.8-2, P=0.305). CONCLUSIONS: In an equal access healthcare system, over a 27-year period there were no significant racial differences in BCR-related, DM-related, and overall death-related outcomes for AA compared to CA men. Access to and receipt of healthcare appears to reduce disparities in outcomes in the military setting. Source of Funding: DOD CDMRP Health Disparities Award # W81XWH-15-1-0381. Disclaimers: The opinions or assertions contained herein are the private ones of the author/speaker and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences or any other agency of the U.S. Government. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e782-e782 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sean Stroup* More articles by this author Audry Robertson More articles by this author Kayla Onofaro More articles by this author Michael Santomauro More articles by this author Nicholas Rocco More articles by this author Huai-ching Kuo More articles by this author Avinash Chaurasia More articles by this author Inger Rosner More articles by this author Timothy Brand More articles by this author John Musser More articles by this author Christopher Porter More articles by this author Grace Lu-Yao More articles by this author Anthony D'Amico More articles by this author Jennifer Cullen More articles by this author Expand All Advertisement PDF downloadLoading ...

A Prospective Study of 18F-DCFPyL PSMA PET/CT Restaging in Recurrent Prostate Cancer following Primary External Beam Radiotherapy or Brachytherapy

Radio-recurrent prostate cancer is typically detected by a rising prostate-specific antigen and may reflect local or distant disease. Positron emission tomography (PET) radiotracers targeting prostate-specific membrane antigen, such as 18F-DCFPyL have shown promise in restaging men with recurrent disease postprostatectomy but are less well characterized in the setting of radio-recurrent disease. A prospective, multi-institutional study was conducted to evaluate the effect of 18F-DCFPyL PET/computed tomography (CT) when added to diagnostic imaging (DI; CT abdomen and pelvis, bone scan, multiparametric magnetic resonance imaging pelvis) for men with radio-recurrent prostate cancer. All men were imaged with DI and subsequently underwent 18F-DCFPyL PET/CT with local and central reads. Tie break reads were performed as required. Management questionnaires were completed after DI and again after 18F-DCFPyL PET/CT. Discordance in patterns of disease detected with 18F-DCFPyL PET/CT versus DI and changes in management were characterized. Seventy-nine men completed the study. Most men had T1 disease (62%) and Gleason score <7 (95%). Median prostate-specific antigen at diagnosis was 7.4 ng/mL and at relapse was 4.8 ng/mL. DI detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 9 out of 79 (11%), distant disease in 12 out of 79 (15%), and no disease in 26 out of 79 (33%). 18F-DCFPyL PET/CT detected isolated intraprostatic recurrence in 38 out of 79 men (48%), regional nodal recurrence in 21 out of 79 (27%), distant disease in 24 out of 79 (30%), and no disease in 10 out of 79 (13%). DI identified 8 out of 79 (10%) patients to have oligometastatic disease, compared with 21 out of 79 (27%) with 18F-DCFPyL PET/CT. 18F-DCFPyL PET/CT changed proposed management in 34 out of 79 (43%) patients. 18F-DCFPyL PET/CT identified extraprostatic disease in twice as many men with radio-recurrent prostate cancer compared with DI and detected a site of recurrence in 87% of men compared with 67% with DI. Furthermore, 18F-DCFPyL PET/CT identified potentially actionable disease (prostate only recurrence or oligometastatic disease) in 75% of men and changed proposed management in 43% of men.

Outcomes and prognostic factors in intermediate-risk prostate cancer: multi-institutional analysis of the Spanish RECAP database.

To retrospectively assess outcomes and to identify prognostic factors in patients diagnosed with intermediate-risk (IR) prostate cancer (PCa) treated with primary external beam radiotherapy (EBRT). Data were obtained from the multi-institutional Spanish RECAP database, a population-based prostate cancer registry in Spain. All IR patients (NCCN criteria) who underwent primary EBRT were included. The following variables were assessed: age; prostate-specific antigen (PSA); Gleason score; clinical T stage; percentage of positive biopsy cores (PPBC); androgen deprivation therapy (ADT); and radiotherapy dose. The patients were stratified into one of three risk subcategories: (1) favourable IR (FIR; GS 6, ≤ T2b or GS 3 + 4, ≤ T1c), (2) marginal IR (MIR; GS 3 + 4, T2a-b), and (3) unfavourable IR (UIR; GS 4 + 3 or T2c). Biochemical relapse-free survival (BRFS), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed. A total of 1754 patients from the RECAP database were included and stratified by risk group: FIR, n = 781 (44.5%); MIR, n = 252 (14.4%); and UIR, n = 721 (41.1%). Mean age was 71years (range 47-86). Mean PSA was 10.4ng/ml (range 6-20). The median radiotherapy dose was 74Gy, with mean doses of 72.5Gy (FIR), 73.4Gy (MIR), and 72.8Gy (UIR). Most patients (88%) received ADT for a median of 7.1months. By risk group (FIR, MIR, UIR), ADT rates were, respectively, 88.9, 86.5, and 86.9%. Only patients with ≥ 24months of follow-up post-EBRT were included in the survival analysis (n = 1294). At a median follow-up of 52months (range 24-173), respective 5- and 10-year outcomes were: OS 93.6% and 79%; BRFS 88.9% and 71.4%; DFS 96.1% and 89%; CSS 98.9% and 94.6%. Complication rates (≥ grade 3) were: acute genitourinary (GU) 2%; late GU 1%; acute gastrointestinal (GI) 2%; late GI 1%. There was no significant association between risk group and BRFS or OS. However, patients with favourable-risk disease had significantly better 5- and 10-year DFS than patients with UIR: 98.7% vs. 92.4% and 92% vs. 85.8% (p = 0.0005). CSS was significantly higher (p = 0.0057) in the FIR group at 5 (99.7% vs. 97.3%) and 10 years (96.1% vs. 93.4%). On the multivariate analyses, the following were significant predictors of survival: ADT (BRFS and DFS); dose ≥ 74Gy (BRFS); age (OS). This is the first nationwide study in Spain to report long-term outcomes of patients with intermediate-risk PCa treated with EBRT. Survival outcomes were good, with a low incidence of both acute and late toxicity. Patients with unfavourable risk characteristics had significantly lower 5- and 10-year disease-free survival rates. ADT and radiotherapy dose ≥ 74Gy were both significant predictors of treatment outcomes.

Practice patterns of primary EBRT with and without ADT in prostate cancer treatment.

Androgen deprivation therapy (ADT) has been shown to improve survival for men with intermediate and high-risk prostate cancer undergoing external-beam radiation therapy (EBRT). Using data from a community-based prospective disease registry, we investigated usage of EBRT with or without neoadjuvant ADT. The CaPSURE database contains 14,863 men with prostate cancer, including 1337 men diagnosed between 1990 and 2014 with localized disease who received EBRT as primary treatment. Prostate cancer risk was calculated using the CAPRA score. Patient characteristics were compared using the Mantel-Haenszel chi-square test for trend and analysis of variance. Between 1990 and 2014, 14,010 men were diagnosed with localized disease within the CaPSURE registry. Of those, 1337 underwent EBRT. Patients had a median age of 71 years. The use of ADT in addition to EBRT increased from 24% in 1990 to 60% in 1996 with a decrease seen to 47% in 2011. Men receiving ADT have differing clinical characteristics including higher PSA at diagnosis, higher Gleason grade, and higher CAPRA scores. Median ADT duration was 4 months. The use of ADT in conjunction with primary EBRT has increased in frequency and duration since 1990. Men receiving ADT have higher risk characteristics than those receiving EBRT alone. There is substantial variability in use of ADT in clinical practice.

Salvage reirradiation for local failure of prostate cancer after curative radiation therapy: Association of rectal toxicity with dose distribution and normal-tissue complication probability models

PurposeThis study aimed to assess the impact of radiation dose on rectal toxicity after salvage external beam radiation therapy (EBRT) with or without a brachytherapy boost for exclusive local failures after the primary EBRT for prostate cancer. Methods and materialsFourteen patients with no severe residual late toxicity after primary EBRT ± brachytherapy were reirradiated after a median time interval of 6.1 years. The median normalized total dose in 2 Gy fractions (NTD2Gy, α/β ratio = 1.5 Gy for prostate cancer cells) was 74 Gy at primary EBRT and 85.1 Gy at reirradiation. Rectal dose-volume histograms (converted to NTD2Gy_alpha/beta = 3 Gy) and the corresponding normal-tissue complication probability (NTCP) values for gastrointestinal (GI) toxicity were evaluated for 2 groups: High GI toxicity (grade ≥3) and low GI toxicity (grade ≤2). ResultsThe 5-year grade ≥3 GI toxicity-free survival rate was 57.1%. The median rectal V70Gy and maximum dose to 1 cm3 (D1ccrect) at primary EBRT were both predictive for grade ≥3 GI toxicity (9% vs 0%; P = .04 and 72.2 Gy vs 66.8 Gy; P < .01, respectively). When adding primary radiation therapy (RT) and reirradiation plans, the median D1ccrect was 139.8 Gy versus 126.7 Gy (P < .01) for high and low GI toxicity groups. NTCP >10% at primary RT was predictive for high GI toxicity at reirradiation (P < .05). ConclusionsEven in the absence of residual toxicity after primary RT, rectal doses >70 Gy and NTCP >10% calculated for a first irradiation may be associated with a higher risk of developing high GI toxicity at reirradiation with a possible D1ccrect threshold of 130 Gy.

The dose distribution in dominant intraprostatic tumour lesions defined by multiparametric MRI and PSMA PET/CT correlates with the outcome in patients treated with primary radiation therapy for prostate cancer

We hypothesized that dominant intraprostatic lesions (DILs) could be depictured by multimodal imaging techniques (MRI and/or PSMA PET/CT) in patients with primary prostate cancer (PCa) and investigated possible effects of radiotherapy (RT) dose distribution within the DILs on the patients’ outcome. One hundred thirty-eight patients with localized prostate cancer (PCa) and visible DIL underwent primary external beam RT between 2008 and 2016 with an aimed prescription dose of 76 Gy to the whole prostate. Seventy-five patients (54%) additionally received androgen deprivation therapy. Three volumes were retrospectively generated: DIL using pretreatment MRI and/or PSMA PET/CT, prostatic gland (PG) and the subtraction between PG and DIL (SPG). The minimum dose (Dmin), maximum dose (Dmax) and mean dose (Dmean) in the three respective volumes were calculated. Biochemical recurrence free survival (BRFS) was considered in uni- and multivariate Cox regression analyses. An explorative analysis was performed to determine cut-off values for the three dose parameters in the three respective volumes. With a median follow-up of 45 months (14–116 months) 15.9% of patients experienced BR. Dmin (cut-off: 70.6 Gy, HR = 0.39, p = 0.036) applied to the DIL had an impact on BRFS in multivariate analysis, in contrast to the Dmin delivered to PG and SPG which had no significant impact (p > 0.05). Dmin was significantly (p 0.05). The dose distribution within DILs defined by PSMA PET/CT and/or MRI is an independent risk factor for BR after primary RT in patients with PCa. These findings support the implementation of imaging based DIL interpretation for RT treatment planning, although further validation in larger patient cohorts with longer follow-up is needed.

Successful treatment of incidentally diagnosed retroperitoneal seminoma with primary external beam radiotherapy

Background Germ cell tumours GCTs are the most common cancer in young men typically arising from the testes However a small subset to appears to originate in other locations and is referred to as primary extragonadal germ cell tumors EGCTs but origin remains controversial New thought is that these so called primary retroperitoneal seminomas uniformly represent metastases from an occult or regressed testicular primary tumour Method We present case report of retroperitoneal seminoma in a year old male patient who presented with bloody diarrhea Endoscopic visualization of colon was normal but imaging confirmed incidental finding of a nodal mass in the abdomen Biopsy report confirmed classic seminoma A gonadal primary was not seen on testicular ultrasound Staging imaging and PET did not identify any other sites of disease Conclusion Our case confirms the excellent response to radiation as monotherapy in retroperitoneal seminoma with no known primary In order to understand this rare neoplasm and serve our patients well more emphasis should be on research for developing novel immunohistochemistry and markers

(ICORG 05-03): prospective randomized non-inferiority phase III trial comparing two radiation schedules in malignant spinal cord compression (not proceeding with surgical decompression); the quality of life analysis

Background: The optimal primary external beam radiation therapy (EBRT) radiation schedule for malignant epidural spinal cord compression (MSCC) remains to be determined. The ICORG 05-03 trial assessed if a 10 Gy single fraction radiation schedule was not inferior to one with 20 Gray (Gy) in five daily fractions, in terms of functional motor outcome, for the treatment of MSCC in patients not proceeding with surgical decompression. This article reports on two of the secondary endpoints, Quality of life (QoL), assessed according to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0 (EORTC Data Center, Brussels, Belgium) and pain control assessed using a visual analog scale.Methods: A randomized, parallel group, multicenter phase III trial was conducted by Cancer Trials Ireland (formerly All-Ireland Cooperative Oncology Research Group, ICORG), across five hospital sites in Ireland and Northern Ireland. Patients were randomized to 10 Gy single fraction of EBRT or 20 Gy in five fractions in a 1:1 ratio. Patients with baseline and 5-week follow up QoL data are included in this analysis.Findings: From 2006 to 2014, 112 eligible patients were enrolled for whom 57 were evaluated for this secondary analysis. After adjusting for pre-intervention scores, there was no statistically significant difference in post-treatment Summary scores (excl. FI and QL), or pain scores between the two RT schedules at 5 weeks and 3 months following EBRT. There was a statistically significant relationship between the pretreatment and post-treatment Summary scores (p = .002) but not between the pre-treatment and post-treatment pain scores.Interpretation: Primary radiotherapy for the treatment of MSCC significantly improves QoL in patients not proceeding with surgical decompression. After adjusting for pre-intervention scores, there was no statistically significant difference between a 10 Gy single fraction radiation schedule and one with 20 Gy in five daily fractions on post-treatment QoL Summary scores. For most patients, an effective treatment with low burden would be desirable. A single fraction schedule should be considered for this group of patients.

Salvage high dose rate brachytherapy after primary external beam irradiation in localized prostate cancer: a case report.

No standard treatment exists for locally relapsed prostate cancer after primary external beam radiotherapy with no evidence of distant metastases. Radical prostatectomy, brachytherapy, cryotherapy and high-intensity focused ultrasound are currently used as local salvage treatments. Data on the safety and effectiveness of high dose rate (HDR) brachytherapy in this scenario are limited. We report on a patient who has no evidence of disease and no late urinary or gastrointestinal toxicity 33 months after receiving HDR treatment for recurrent prostate cancer.

Primary radiotherapy with endobronchial high-dose-rate brachytherapy boost for inoperable lung cancer: long-term results.

To retrospectively evaluate the outcome of patients with inoperable non-small-cell lung cancer treated with primary external beam radiotherapy combined with high-dose-rate endobronchial brachytherapy boost. Between 1988 and 2005, 35 patients with non-small-cell lung cancer (stage I-III) ineligible for surgical resection and/or chemotherapy, were primarily treated with external beam radiotherapy with a median total dose of 50 Gy (range, 46-60). A median of 3 fractions high-dose-rate endobronchial brachytherapy was applied as a boost after external beam radiotherapy, the median total dose was 15 Gy (range, 8-20). High-dose-rate endobronchial brachytherapy was carried out with iridium-192 sources (370 GBq) and prescribed to 1 cm distance from the source axis. With a median follow-up of 26 months from the first fraction of high-dose-rate endobronchial brachytherapy, the 1-, 2- and 5-year overall (local progression-free) survival rates were 76% (76%), 61% (57%) and 28% (42%), respectively. Complete or partial remission rates 6 to 8 weeks after treatment were 57% and 17%, respectively. Significant prognostic favorable factors were a complete remission 6-8 weeks after treatment and a negative nodal status. In patients without mediastinal node involvement, a long-term local control could be achieved with 56% 5-year local progression-free survival. Common Toxicity Criteria grade 3 toxicities were hemoptysis (n = 2) and necrosis (n = 1). One fatal hemoptysis occurred in combination with a local tumor recurrence. The combination of external beam radiotherapy with high-dose-rate endobronchial brachytherapy boost is an effective primary treatment with acceptable toxicity in patients with non-small-cell lung cancer ineligible for surgical resection and/or chemotherapy.