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Background and purpose: In men with biochemical recurrence (BCR) of prostate cancer (PCA) after radical prostatectomy (RP), there is limited data on effectiveness of adding elective pelvic nodal radiation (EPNI) to salvage prostate bed radiation (PBRT) without androgen deprivation therapy (ADT) to prevent progression. Materials and Methods: Retrospective chart review of 326 patients treated for BCR of PCA from a single institution was performed to capture baseline pre-operative PSA, pathologic details, post-operative PSA, treatment details (radiation and ADT), subsequent failure (rising PSA), response to radiation, and subsequent outcomes after radiation. Results: Between 2004 through 2017, 326 patients received PBRT. Majority (n = 253; 78%) did not receive ADT. Majority received EPNI (n = 227; 90%) with salvage PBRT (n = 213; 94%). The median pre-PBRT PSA was 0.50 ng/ml (0.10–75.60 ng/ml). Of the patients that did not receive ADT, 83% (210/253) achieved an undetectable (

Purpose: Typical doses of 45–50.4 Gy used to treat regional nodes have demonstrated inadequate control of gross nodal disease (GND) in gynecologic cancer, and accelerated repopulation may limit the efficacy of a sequential boost. We reviewed outcomes of patients treated with a simultaneous integrated boost (SIB) at 2.25 Gy per fraction to positron emission tomography (PET) avid GND to evaluate toxicity and tumor control using this dose-escalated regimen.Materials and Methods: A total of 83 patients with gynecologic cancer and PET avid inguinal, pelvic, or para-aortic lymphadenopathy were treated using intensity-modulated radiation therapy (IMRT) with SIB. Primary cancers were mostly cervical (51%) and endometrial (34%), and included patients who received concurrent chemotherapy (59%) and/or brachytherapy boost (78%).Results: Median follow-up from radiation completion was 12.6 months (range, 2.7 to 92.9 months). Median dose to elective lymphatics was 50.4 Gy (range, 45 to 50.4 Gy) at 1.8 Gy/fraction. Median SIB dose and volume were 63 Gy (range, 56.3 to 63 Gy) and 72.8 mL (range, 6.8 to 1,134 mL) at 2–2.25 Gy/fraction. Nodal control was 97.6% in the SIB area while 90.4% in the low dose area (p = 0.013). SIB radiotherapy (RT) field failure-free, non-SIB RT field failure-free, and out of RT field failure-free survival at 4 years were 98%, 86%, and 51%, respectively. Acute and late grade ≥3 genitourinary toxicity rates were 0%. Acute and late grade ≥3 gastrointestinal toxicity rates were 7.2% and 12.0%, respectively.Conclusion: Dose escalated SIB to PET avid adenopathy results in excellent local control with acceptable toxicity.

Androgen deprivation therapy (ADT) is known to cause a decline in hemoglobin (Hgb), but the effect on other blood parameters is less well studied. In the lab, androgen manipulation has an effect on leukocyte counts. We evaluated the effects of androgen ablation alone on Hgb, white blood cell (WBC), granulocyte, and lymphocyte counts in 99 prostate cancer patients. In addition, since radiation therapy decreases those counts, we evaluated whether the addition of ADT makes it worse, comparing 162 patients receiving both radiation and ADT to 149 patients with radiation alone. ADT alone did significantly (but minimally) cause a drop in the Hgb (~0.5 g/dl), the WBC (-0.39 × 103/μl) and granulocyte (-0.32 × 103/μl), but not the lymphocyte counts. The combination of ADT with radiation did cause a greater decline in the Hgb levels at the end of treatment, but at follow up there was no difference. There was no additional effect on WBC, granulocytes or lymphocyte counts. Our results confirm clinically that ADT alone has minimal effect on WBC and its components and that there is no synergistic detriment of androgen ablation on the effects of radiation therapy on those cells.

Introduction C-reactive protein (CRP) is an acute-phase reactant used as a general marker for inflammation. Isolated levels have been associated with prostate cancer development, prostate-specific antigen (PSA), Gleason score, and treatment response. We seek to establish whether CRP levels reflect inflammation caused by prostate cancer by comparing levels at various points of time before, during, and after therapy. Materials and methods A total of 209 patients had a complete blood count (CBC), PSA, and CRP taken at up to four different time points. Labs were performed up to one week prior to androgen ablation via leuprolide injection (pre-AA), up to one week prior to radiotherapy (RT) (pre-RT), within one week of RT completion (post-RT), and three months following RT completion (FU [follow-up]). Results Significant relationships were found between CRP and WBC pre-AA (p-value=0.0050), pre-RT (p-value=0.0170), and post-RT (p-value=0.0113), but not at FU (p=.096). CRP had no significant relationship with PSA or lymphocytes at any time points. PSA was significantly affected by androgen ablation but lymphocytes, WBCs, and CRP were not. No CRP levels were associated with risk groups or FU-PSA. Lymphatic radiation fields significantly decreased WBCs and lymphocytes but not CRP. PSA, WBC, and lymphocytes all significantly decreased from pre-RT to post-RT, followed by a significant recovery. CRP did not significantly change during any of these periods and was not significantly related to changes in PSA, WBCs, or lymphocytes. Conclusion CRP is not a sensitive marker of the acute inflammatory effects of non-metastatic prostate cancer and treatment response with androgen ablation or radiation therapy.

Background We measure the impact of pelvic lymph node radiotherapy (PLNRT) of two doses using conventional fractionation on long term quality of life (QOL) in prostate cancer. Methods Prostate cancer patients recorded baseline scores using the Expanded Prostate Cancer Index Composite (EPIC), prior to definitive or post-prostatectomy radiotherapy. If ENI was given, it was to 45 or 54 Gy. New scores were recorded 20–36 months after radiotherapy. Absolute change in each domain subscale and summary score was recorded as well as if this change met criteria for minimally important difference (MID), with separate multivariate analysis (MVA) for both measures. Subsequent dosimetric analysis was performed. Results Frequency of a MID decline was significantly greater in patients treated with ENI to 54 Gy for urinary function, incontinence, and overall. No urinary decline was correlated with PLNRT to 45 Gy. PLNRT to 54 Gy was significant for decline in urinary function, bother, irritative, incontinence, and overall score in one or both MVA models while 45 Gy was not. Postoperative status was significant for decline in urinary function, incontinence, and overall. Amongst postoperative patients, there was significantly greater decline in urinary function score in the salvage setting. Neither 54 nor 45 Gy significantly affected bowel subscale or overall score decline. Conclusions Using conventional fractionation, adding PLNRT to 54 Gy, but not 45 Gy, correlates with worse urinary QOL, with postoperative patients experiencing a steeper decline. PLNRT had no significant impact on bowel QOL with either dose.

PURPOSE My journey to the stars began as I - along with the whole world - stood still and watched Neil Armstrong take those first small steps on the Moon. Fast forward 50 years and NASA astronauts Scott Kelly and Christina Koch each spend nearly a year in space aboard the International Space Station (ISS), a remarkable multinational collaborative project and floating U.S. National Laboratory that has supported continuous human presence in low Earth orbit for the past 20 years. Marking a new era of human space exploration, the first commercial rocket, SpaceX Falcon 9, recently launched NASA astronauts Doug Hurley and Bob Behnken in the Crew Dragon spacecraft Endeavor to the ISS and returned safely to Earth. NASA and its commercial partners are rapidly advancing innovative space technologies, and with the recently announced Artemis team of astronauts, plans to send the first woman and next man back to the moon and establish sustainable exploration by the end of the decade. Humankind will then be poised to take the next giant leap - pioneering human exploration of Mars. CONCLUSIONS Historically, fewer than 600 individuals have participated in spaceflight, the vast majority of whom have been middle aged males (35-55 years) on short duration missions (less than 20 days). Thus, as the number and diversity of space travelers increase, a better understanding of how long-duration spaceflight affects human health is essential to maintaining individual astronaut performance during, and improving disease and aging trajectories following, future exploration missions. Here, I review findings from our NASA Twins Study and Telomeres investigations, highlighting potential mechanistic roles of chronic space radiation exposure in changes in telomere length and persistent DNA damage responses associated with long-duration spaceflight. Importantly, similar trends were observed in prostate cancer patients undergoing intensity-modulated radiation therapy (IMRT), additional support specifically for the role of radiation exposure. Individual differences in response were also observed in both cohorts, underscoring the importance of developing personalized approaches for evaluating human health effects and long-term outcomes associated with radiation exposures, whether on Earth or living in the extreme environment of space.

Introduction Patients have increasing longevity and time for bone healing following radiotherapy (RT) for treatment of bone metastases (BM). Attempts to assess the treatment response of bone metastases have been either limited or heavily subjective. Our goal was to try to quantitate cancer-involved bone changes after RT using changes in bone mineral density (BMD) from computer tomographic (CT) imaging. Methods Retrospectively, 117 spinal metastases were identified that received RT with follow-up CT scans >9 months following CT simulation. Contoured volumes included: the metastasis (gross tumor volume; GTV); the involved vertebra (gross bone volume; GBV); a total lytic volume (Lyt); a dominant lytic volume (Domlyt); a control volume, and the nearest uninvolved, unirradiated vertebra (control bone volume; CBV). The Hounsfield-density calibration curve was used to measure the density of these volumes before and after treatment. Results Whether using raw or control-adjusted changes, the absolute and percent change in density of the GBV, GTV, Lyt, and Domlyt volumes all significantly increased (each p

Highlights • Radiation therapy alone has dramatic effects on lymphocyte subgroups. • CD4+, CD8+ and CD56+ counts drop by >70%, CD 19+ by >90%. • Three months post exposure, no subgroup has returned to baseline levels. • All subgroups except CD 56+ (including CD19+) recovered modestly to about 40% of pre-treatment levels. • CD56+ were more resistant and recovered to 64% of pretreatment levels. • CD56+ cells recover more fully (to >60% of pretreatment levels)., There is a lack of information on the radiosensitivity of lymphocyte subgroups to radiation alone. CD4+ and CD8+ lymphocytes respond similarly. CD 19+ dropped most precipitously, but recovered to levels similar to the other subgroups by 3 months. NK cells decline more modestly and recover more fully by 3 months.

PURPOSE/OBJECTIVE(S) Despite the potential for improved local control, there is little data on long term quality of life (QoL) outcomes using dose escalated nodal radiotherapy (RT) in prostate cancer with conventional fractionation. We compare QOL following RT with conventional, dose-escalated, or no nodal irradiation. MATERIALS/METHODS From 2009 to 2017, 445 patients with low-risk to high-risk prostate cancer recorded baseline scores using the Expanded Prostate Cancer Index Composite (EPIC), prior to definitive or post-prostatectomy (PP) radiation. Each subsequently completed a new EPIC 18-36 months after intensity modulated RT. Absolute change in each domain summary and subscale score was recorded as well as if the change met minimally important difference (MID) criteria. All baseline comparisons were done using bivariate analysis methods. Multivariate analysis (MVA) was performed using a generalized linear model to assess changes in each domain summary and sub-scale score. MVA was performed with a proportional odds model to assess MID changes. Variables were age, RT setting (definitive or PP), pre-treatment score, and nodal dose. P-value significance was set to < 0.05. RESULTS Prescribed nodal dose was 0 Gy, 45-51 Gy, and ≥54 Gy in 31%, 8%, and 61% of patients, respectively. Radiation was given PP in 37% of patients. PP patients had significantly worse baseline urinary function, incontinence, and overall scores. In each MVA, PP was associated with greater decreases of urinary function, incontinence, and overall scores following RT. Prior prostatectomy was not associated with a significant difference in the bowel, hormonal, or sexual domains. Including all RT settings, median changes reported in urinary function, bother, incontinence, and overall scores were: for 54 Gy, -4.1, 0.0, -6.3, and -2.4; for 45-51 Gy, 0.0, -3.6, 0.0, and -0.7; for 0 Gy 0.0, 0.0, 0.0, and 0.0. MVA showed that nodal irradiation to ≥ 54 Gy was significantly correlated with greater decreases of urinary function, bother, incontinence, and overall score in one or both models. Nodal irradiation to ≥ 54 Gy was not found to be significantly correlated with changes in the bowel, hormonal, or sexual domains. Nodal irradiation to 45 Gy was not significantly associated with any domain or subscale change. CONCLUSION Compared to no nodal irradiation, escalated nodal irradiation to ≥54 Gy was associated with a small but significantly worse urinary QOL while 45 Gy was not. Escalated nodal irradiation to ≥54 Gy was not associated with worse bowel QOL. Prior prostatectomy was associated with a greater decrease in urinary QOL following RT. Clinical judgement should be used to balance the benefits and toxicities of nodal irradiation in prostate cancer.

Objectives We evaluated how the changes in Gleason grading affected the long-term outcomes of a large prostatectomy cohort. Methods We obtained long-term follow-up (16.7 years) in 581 patients having undergone radical retropubic prostatectomy between 1985 and 1995. We excluded those with seminal vesicle and/or lymphatic involvement. We regraded the specimens according to contemporary guidelines and compared how this affected outcomes compared with their original (pre-1995) Gleason scoring. In total, 499 patients were evaluable. Results A Gleason score of 6 or less declined from 73% to 29%, and the number increased from 25% to 63% for a Gleason score of 7 and from 5% to 8% for a Gleason score of 8 to 9. As a result, for a Gleason score less than 7, biochemical failure decreased from 28% to 23%, metastatic disease 5% to 2%, and prostate cancer death from 5% to 3%. The same results were 50% to 37%, 11% to 7%, and 10% to 6% for a Gleason score of 7 and 86% to 71%, 43% to 32%, and 29% to 26% for a Gleason score more than 7, respectively. With the most recent grade grouping, for groups 1 to 5, biochemical failure occurred in 23%, 32%, 45%, 69%, and 78%, respectively. Metastatic disease occurred in 2%, 4%, 12%, 24%, and 56%, respectively. Prostate cancer–related death occurred in 2%, 4%, 9%, 21%, and 44%, respectively. Conclusions The revised Gleason scores improved the outcomes in all risk groups. Based on Gleason score, patients with prostate cancer will appear to have better outcomes than they did before 2005, making any comparison tenable. The current grading system shows a consistent increased risk in biochemical failure, metastatic disease, and prostate cancer–related death with each successive grade.

Background Prostate cancer treatment aims to prevent metastases and disease‐specific mortality. Pathologic parameters have limited ability to predict these outcomes, but biomarkers can improve risk discrimination. We evaluated the ability of cell‐cycle progression and combined cell‐cycle risk scores to predict metastases and disease‐specific mortality after prostatectomy. Methods Eligibility included (1) treatment with radical prostatectomy (1985–1997); (2) cell‐cycle progression score; (3) preoperative prostate‐specific antigen; (4) no neoadjuvant therapy; and (5) clinical follow‐up (N = 360). Cancer of the prostate risk assessment postsurgical score was combined with cell cycle progression into the prespecified combined cell‐cycle risk score. Hazard ratios (HRs) are reported per unit score. Results In total, 11% (41/360) developed metastases and 9% (33/360) experienced disease‐specific mortality. Combined cell‐cycle risk score predicted metastases and disease‐specific mortality post‐radical prostatectomy (p

The ability to predict a cancer patient’s response to radiotherapy and risk of developing adverse late health effects would greatly improve personalized treatment regimens and individual outcomes. Telomeres represent a compelling biomarker of individual radiosensitivity and risk, as exposure can result in dysfunctional telomere pathologies that coincidentally overlap with many radiation-induced late effects, ranging from degenerative conditions like fibrosis and cardiovascular disease to proliferative pathologies like cancer. Here, telomere length was longitudinally assessed in a cohort of fifteen prostate cancer patients undergoing Intensity Modulated Radiation Therapy (IMRT) utilizing Telomere Fluorescence in situ Hybridization (Telo-FISH). To evaluate genome instability and enhance predictions for individual patient risk of secondary malignancy, chromosome aberrations were also assessed utilizing directional Genomic Hybridization (dGH) for high-resolution inversion detection. We present the first implementation of individual telomere length data in a machine learning model, XGBoost, trained on pre-radiotherapy (baseline) and in vitro exposed (4 Gy γ-rays) telomere length measures, to predict post-radiotherapy telomeric outcomes, which together with chromosomal instability provide insight into individual radiosensitivity and risk for radiation-induced late effects.

Aim We sought to evaluate the effect of radiation therapy on post-prostatectomy urinary quality of life in prostate cancer patients. Background In some men with non-metastatic prostate cancer, radiation therapy is indicated following prostatectomy. The radiation toxicity and quality of life considerations are unique in the post-prostatectomy setting. Materials and methods A total of 106 patients receiving post-prostatectomy radiation therapy completed the Expanded Prostate Cancer Index Composite questionnaire before radiation and at 2-year follow-up. The primary outcomes of this study were the urinary domain summary score and subscale scores. Planned analysis was performed based on time interval from prostatectomy to radiation therapy. Results Among the 106 patients analyzed, the mean urinary domain summary score worsened at 2-year follow-up after radiation therapy, lowering from 77.23–72.51 (p = 0.0085). Similar worsening was observed in the subscales of function (p = 0.003), bother (p = 0.0397), and incontinence (p = 0.0003). Urinary incontinence showed the greatest observable change among subscales. While the summary score worsened (p = 0.0031) among patients receiving radiation therapy more than 1 year after prostatectomy, it did not show statistically significant change in those treated 1 year or less after prostatectomy. Conclusion Our results demonstrate that post-prostatectomy radiation therapy is associated with modest declines in reportable urinary quality of life. Patients receiving radiation therapy more than 1 year after prostatectomy showed greater worsening of urinary quality of life, which indicates that there may be no functional advantage to delaying radiation therapy beyond the initial postoperative period.

Background. Only truly long-term follow-up can determine the ultimate outcome in prostate cancer. Most studies have a median follow-up of less than 10 years and then project outcomes out to 15 and 20 years. We sought to follow patients for at least 20 years. Materials and Methods. We followed 754 prostate cancer patients treated with radical prostatectomy from 1988 to 1995 for a median follow-up (in survivors) of 23.9 years. We excluded lymph node and seminal vesicle positive patients and an additional 47 patients that did not have baseline prostate-specific antigen (PSA). This left 581 patients for analysis. Results. With the factors of PSA, Gleason score, and extraprostatic extension/margin positivity, we could partition patients into three risk groups for biochemical failure (low, intermediate, and high). In further analysis, we found that the risk of metastatic disease in the first two groups was almost identical (4% and 5%, respectively), while it was 19% in the high-risk group. High-risk patients were those with PSA >20 ng/ml and/or Gleason >7, or Gleason 7 + PSA 10–20 + epe (and or margin) positive. They had a 22% prostate cancer mortality. Conclusion. In patients with truly long-term follow-up after prostatectomy for prostate cancer, the risk of metastatic disease and cancer death is very low. Patients with the lower risk findings do not appear to benefit from routine follow-up after 10 years free of biochemical recurrence. With a higher risk of later failure, we recommend that the higher risk patients be followed at least intermittently for another 5 years (out to 15 years).

Radiation therapy (XRT) is a standard treatment for prostate cancer (PCa). Although dose escalation increases local control, toxicity hampers further escalation. Broader improvement will be possible by the addition of adjuvant therapies, which can synergize with radiation and thus improve efficacy. We have identified a natural compound (Nexrutine, Nx) that inhibits the survival and growth of PCa cells in combination with radiation. Combination studies demonstrated strong interaction between Nx and radiation both in vitro in multiple PCa cell lines and in the Transgenic adenocarcinoma of mouse prostate (TRAMP) model. Nx potentiated growth inhibitory effects of IR by down regulating ribosomal protein S6K (RPS6KB1), CyclinD1, Chk1 and HIF-1 α and prolonging G2/M checkpoint block. RPS6KB1 is upregulated in prostate cancers and its expression is correlated with tumor grade. Knockdown of RPS6KB1 in PCa cells increased their sensitivity toward radiation-induced survival inhibition. Overall, we provide scientific evidence (i) in support of Nx as an adjuvant in PCa patients receiving XRT (ii) suggesting that RPS6KB1 is an important player in Nx-mediated combinatorial benefits and emphasizes that RPS6KB1 is a novel target for PCa treatment. These data underscore the need to test the agent in additional preclinical models to validate these observations.

Introduction:This research quantifies and compares the effect of hip prostheses on dose distributions calculated using collapsed cone convolution superposition and Monte Carlo (with and without correcting for the density of the implant and surrounding tissues). The use of full volumetric modulated arc therapy arcs versus volumetric modulated arc therapy arcs avoiding the hip implants (skip arcs) was also studied.Materials and Methods:Six prostate patients with hip prostheses were included in this study. The hip prostheses and the streaking artifacts on the computed tomography images were contoured by a single physician, and full volumetric modulated arc therapy arcs were created in the Pinnacle3 TPS. Copies of each plan were made, and the doses were recalculated with the densities of the prostheses and surrounding tissues overridden. The plans were then exported to Monaco and recalculated using a Monte Carlo dose calculation algorithm, with and without densities of the prosthesis and surrounding tissues overridden.Results:With density overrides, Pinnacle3 had a 4.4% error for ion chamber measurements. Monaco was within 0.2% of ion chamber measurement when density overrides were used. On average, when density overrides were used in Pinnacle3 for patient dose calculations, the planning target volume D95 value dropped from 99.3% to 82.7%. Monaco also showed decreased planning target volume coverage when plans were recalculated with correct density information. Full arc plans (with density overrides) for the patient with a bilateral prosthesis provided significant bladder sparing and some rectal sparing compared to skip arc plans.Conclusion:When planning for prostate patients with hip prostheses, correct density information for implants and surrounding tissues should be used to optimize the plan and ensure optimal accuracy. If available, a Monte Carlo algorithm should be used as a second check. Full arcs could be used to spare dose to organs at risk, while maintaining adequate planning target volume coverage, when using a Monte Carlo dose calculation algorithm.

Introduction: High Grade Prostatic Intraepithelial Neoplasia (HGPIN) was originally thought to be a cancer precursor, but subsequent data has questioned its prognostic significance. We analyzed a large cohort of men diagnosed with HGPIN for subsequent occurrence of prostate cancer. Methods: From 2001 to 2011, we identified 567 men with isolated HGPIN and followed them for subsequent diagnosis of prostate cancer. Results: Two hundred and five patients were followed (median 5.9 years) without biopsy and remained clinically free of prostate cancer. The remaining 362 men underwent repeat biopsies and 133 (37%) were diagnosed with prostate cancer. The number of cores of HGPIN and whether they were unilateral or bilateral was not predictive for subsequent diagnosis of cancer. Prostate specific antigen was the only statistically significant predictor for prostate cancer. Conclusions: We found the incidence of cancer after a diagnosis of HGPIN to be 37%, which is consistent with other published series. This is only marginally higher than in patients re-biopsied after a prior benign biopsy. It appears that isolated HGPIN has only a small predictive value for subsequent diagnosis of prostate cancer. Therefore the finding of HGPIN should be used only in conjunction with other risk factors and patient considerations in deciding whether to proceed with further prostate biopsies.

Background: Historically, ploidy and S phase percentage appeared to be promising predictors for prostate cancer recurrence. Lack of uniformity and consistency hampered their development. We evaluated ploidy and S phase for prostate cancer death in a cohort of patients with long-term follow-up. Methods: We identified 127 patients that had ploidy and S phase determined at the time of their radical prostatectomy for prostate cancer. With 15 years of follow-up, we determined the risk of biochemical failure and risk of death from prostate cancer. We correlated the S phase and ploidy findings with standard pathology findings. Results: A total of 107 (84%) had diploid and 20 (16%) had non-diploid cancers. The median S phase was 6.6%. There was no correlation of ploidy (P = 0.472) or S phase with preoperative PSA or Gleason score. On univariate analysis, EPE, margin positivity, seminal vesicle involvement, lymph node involvement, high Gleason score and PSA > 10 ng/mL were all predictive of biochemical failure. Ploidy and S phase were not. For prostate cancer death, only Gleason score was predictive. Conclusions: With long-term follow-up in our cohort, Gleason score was predictive of prostate cancer death. Ploidy and S phase were not predictive for biochemical failure or prostate cancer mortality. World J Oncol. 2018;9(3):69-73 doi: https://doi.org/10.14740/wjon1111w

Purpose/Objective(s) It is accepted that radiation therapy can have some effect on hemoglobin/hematocrit, but it is not very well documented. The purpose of this study is to explore the effect of radiation monotherapy on hematocrit levels. Materials/Methods Given that intensity modulated radiation therapy treats a large volume of normal tissue, we were concerned about the unrecognized effects of pelvic radiation therapy on blood counts. We prospectively obtained complete blood counts (CBCs) pretreatment, the end of treatment and 3 months post-RT from 2014-2016. With IRB approval we conducted a retrospective analysis of 221 patients treated with pelvic radiation for prostate adenocarcinoma. Given that the lifespan of RBCs is 120 days, we used the 3-month counts (approximately 130 days after 20 Gy is delivered). Dose volume histograms (DVHs) corresponding to 8 different contoured structures in the pelvis that were deemed significant in order to look for a correlation between pelvic structures and values of the CBC. These patients received either primary prostate radiation to 78 Gy total dose, or post-prostatectomy radiation for recurrence to 70 Gy total dose. Additionally, most of these patients had pelvic lymphatic irradiation (common iliac, external iliac, and internal iliac) to 54 Gy. Some patients received concomitant androgen ablation. Results Upon analysis, affected values were the RBC count, hemoglobin, and hematocrit. Hematocrit demonstrated the strongest correlation. Overall, the mean hematocrit dropped from 42.01% to 38.41% (8.57% decrease). Irradiated pelvic structures that correlated with significant decreases in hematocrit were the following: the bone volume of os coxae bilaterally superior to the acetabulum (OCUB), the entire os coxae bilaterally (OCTB), and the whole pelvis (BVWP). The OCUB showed the highest correlation, with a maximum AUC of 0.74 at V20 Gy with a volume threshold of 30%; odds ratio (OR) 9.8; confidence interval (CI) 2.9-32.9. Dose to the OCUB, showed an AUC of 0.73 with a dose of 23 Gy (OR 2.7, CI 1.3-5.6). For OCTB, maximum AUC of 0.69 was observed at V20 Gy where the volume threshold was 50%, (OR 9.3, CI 2.7-31.8). Mean dose analysis showed an AUC of 0.69 where the dose threshold was 28 Gy, odds ratio was 1.4 and CI 0.5-3.9 (not statistically significant). For BVWP a maximum AUC of 0.71 was seen at V20 Gy where the volume threshold was 40%, (OR 7.5, CI 2.2-25.4). Mean dose analysis showed an AUC of 0.72 where the dose threshold was 24 Gy, odds ratio was 2.6 and CI 1.1-6.1. Conclusion These findings confirm the most radiosensitive sites of bone marrow in the pelvis. The doses to OCUB, OCTB and BVWP were found to correlate with a significant drop of hematocrit. A threshold of V20 Gy

Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy.Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL.A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression-free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P.0001). The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P.05). The mean nadir temperature reached for cryotherapy patients was -35°C (range, -96°C to -6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles).Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criteria for consideration of cryotherapy and brachytherapy are similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular patient subset.

Purpose Bladder preservation therapy is an effective treatment for muscle-invasive urothelial carcinoma (UC). In this study we treated noncystectomy candidates with daily radiation and weekly paclitaxel for 7 weeks. Patients whose tumors showed her2/neu overexpression were additionally treated with weekly trastuzumab. Methods and Materials Sixty-eight evaluable patients were treated with radiation therapy and either paclitaxel + trastuzumab (group 1) or paclitaxel alone (group 2). Groups were assigned on the basis of her2/neu immunohistochemistry results. Patients received 1.8-Gy fractions to a total dose of 64.8 Gy. The primary endpoint of the study was treatment-related toxicity, and secondary endpoints included complete response (CR) rate, protocol completion rate, and survival. Results A total of 20 evaluable patients were treated in group 1 and 46 patients in group 2. Acute treatment-related adverse events (AEs) were observed in 7 of 20 patients in group 1 (35%) and 14 of 46 patients in group 2 (30.4%). Protocol therapy was completed by 60% (group 1) and 74% (group 2) of patients. Most incompletions were due to toxicity, and the majority of AEs were gastrointestinal, including 1 grade 5 AE (group 1). Two other deaths (both in group 2) were unrelated to protocol therapy. No unexpected cardiac, hematologic, or other toxicities were observed. The CR rate at 1 year was 72% for group 1 and 68% for group 2. Conclusions In patients with muscle-invasive UC who are not candidates for cystectomy, daily radiation combined with paclitaxel is an effective treatment strategy with a high completion rate and moderate toxicity. In patients with her2/neu-positive tumors, a group generally considered to have worse outcomes, the addition of trastuzumab appears to result in comparable efficacy and toxicity. Further biomarker-driven trials should be undertaken in advancing treatment of this challenging disease.

Purpose/objectiveHypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG Oncology/RTOG 0415 low-risk prostate cancer trial (N = 521).Material/methodsTreatment in the studied HRT arm was delivered as 70 Gy at 2.5 Gy/fraction with 3D-CRT/IMRT (N = 108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/rectum: α/β = 6 Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p ≤ 0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUCvalidation) was within AUCtraining ± SD with p ≤ 0.05, and with an Hosmer-Lemeshow p-value (pHL) > 0.05.ResultsThree candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume

The ability to predict a cancer patient’s response to radiotherapy and risk of developing adverse late health effects would greatly improve personalized treatment regimens and individual outcomes. Telomeres represent a compelling biomarker of individual radiosensitivity and risk, as exposure can result in dysfunctional telomere pathologies that coincidentally overlap with many radiation-induced late effects, ranging from degenerative conditions like fibrosis and cardiovascular disease to proliferative pathologies like cancer. Here, telomere length was longitudinally assessed in a cohort of fifteen prostate cancer patients undergoing Intensity Modulated Radiation Therapy (IMRT) utilizing Telomere Fluorescence in situ Hybridization (Telo-FISH). To evaluate genome instability and enhance predictions for individual patient risk of secondary malignancy, chromosome aberrations were assessed utilizing directional Genomic Hybridization (dGH) for high-resolution inversion detection. We present the first implementation of individual telomere length data in a machine learning model, XGBoost, trained on pre-radiotherapy (baseline) and in vitro exposed (4 Gy γ-rays) telomere length measurements, to predict post radiotherapy telomeric outcomes, which together with chromosomal instability provide insight into individual radiosensitivity and risk for radiation-induced late effects.

5524 Background: Prostate cancer treatment aims to prevent metastatic disease (METS) and disease-specific mortality (DSM). A major challenge is to identify those at highest risk so additional intervention can be initiated earlier when it has a better chance of success. Pathologic parameters alone have limited ability to predict METS and DSM, but data suggests biomarkers can improve risk discrimination. Methods: Eligible patients had: (1) prostate cancer treated with radical prostatectomy (RP; 1988-1995); (2) available tissue for cell-cycle progression (CCP) testing that resulted in a valid score; (3) preoperative prostate-specific antigen (PSA); (4) no neoadjuvant therapy; and (5) clinical follow-up (N = 360). Cancer of the prostate risk assessment post-surgical (CAPRA-S) was combined with CCP into a combined cell-cycle risk score (CCR = 0.38 × CAPRA-S + 0.57 × CCP). Results: Median follow-up was 23.5 years for patients alive at last follow-up. Overall, 11% (41/360) developed METS and 9% (33/360) had DSM. CCP score added significant information to CAPRA-S when predicting METS (p = 0.001) and DSM (p = 0.001). CCR score was also a significant predictor of METS and DSM (p-values < 1×10−8). CCP and CCR scores were prognostic of METS in patients with rising post-RP PSA. Of patients with biochemical recurrence (BCR), 25% (41/163) developed METS. CAPRA-S alone was predictive of these events (p = 0.01) but was significantly improved with the addition of CCP (Hazard Ratio [HR] = 1.69 [95% Confidence Interval (CI) 1.13, 2.52], p = 0.014). CCR was also highly prognostic (HR = 1.56 [95% CI 1.20, 2.03], p = 0.001). CCR score discriminated risk of METS both post-RP and after post-RP BCR (Table). Conclusions: Overall, the CCR score significantly predicted METS and DSM in prostate cancer post-RP and was also highly prognostic in those with a post-RP rising PSA. It is therefore a useful tool for determining who is at greatest risk of treatment failure and may benefit from earlier intervention. [Table: see text]

Objectives: To review our two institutional experiences regarding the historical referral patterns of bladder cancer patients to receive radiation therapy, characteristics of these referred patients, and their treatment outcomes. Methods: A retrospective review was performed analyzing patients who underwent radiation therapy for bladder cancer from 2005 to 2015 ( n = 69) at two regional referral institutions. The age-adjusted Charlson comorbidity index (AACCI) was calculated for each patient. Patients were divided into three groups: definitive concurrent chemoradiation (CCR), aggressive radiation (AR) alone ≥ 50 Gy, or palliative radiation alone (PR) < 50 Gy. Gastrointestinal (GI) and genitourinary (GU) acute toxicities were recorded. Results: The median overall AACCI score was 7, which correlates to a two-year expected survival of 55% ± 11%. Thirty-five (50.7%) patients received CCR, 19 (27.5%) received AR, and 15 (21.7%) received PR. Patients presented with hematuria ( n = 43, 62%), pain (n = 18, 26%), or obstruction ( n = 12, 17%). Of symptomatic patients, treatment improved hematuria in 86%, pain in 75%, and obstruction in 42%. Twenty-two recurrences (32%) were identified at follow-up. Local, regional, and distant recurrences developed in 20%, 14%, and 17% of patients who received CCR. There were two grade 3 GU toxicities and one grade 3 GI toxicity; all grade 3 toxicities were in patients receiving CCR. Conclusions: Bladder preservation is possible with chemoradiation therapy; however, urologists rarely refer patients for consideration of chemoradiation. The limited patients who are referred for radiation generally have limited life expectancy, significant comorbidities, or have advanced disease amenable only to palliation. Palliative radiation improves symptoms with minimal toxicity.

Purpose Patients with high-risk prostate cancer after radical prostatectomy are at risk for death. Adjuvant androgen-deprivation therapy (ADT) may reduce this risk. We hypothesized that the addition of mitoxantrone and prednisone (MP) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone. Methods Eligible patients had cT1-3N0 prostate cancer with one or more high-risk factors after radical prostatectomy (Gleason score [GS] ≥ 8; pT3b, pT4, or pN+ disease; GS 7 and positive margins; or preoperative prostate-specific antigen [PSA] > 15 ng/mL, biopsy GS score > 7, or PSA > 10 ng/mL plus biopsy GS > 6. Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage, GS, and adjuvant radiation plan and randomly assigned to ADT (bicalutamide and goserelin for 2 years) or ADT plus six cycles of MP. The primary end point was overall survival (OS). Median OS was projected to be 10 years in the ADT arm, requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92% power and one-sided α = .05. Results Nine hundred sixty-one eligible intent-to-treat patients were randomly assigned to ADT or ADT + MP from October 1999 to January 2007, when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP. Median follow-up was 11.2 years. The 10-year OS estimates were 87% with ADT (expected 50%) and 86% with ADT + MP (hazard ratio, 1.06; 95% CI, 0.79 to 1.43). The 10-year estimate for disease-free survival was 72% for both arms. Prostate cancer was the cause of death in 18% of patients in the ADT arm and 22% in the ADT + MP arm. More patients in the MP arm died of other cancers (36% v 18% in ADT alone arm). Conclusion MP did not improve OS and increased deaths from other malignancies. The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates, although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm.

p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity. Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy. Patients scheduled to receive minimum 4 cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose escalation of LDA started at 0.005 mg/kg/day for 3 days. This dose satisfied objective 1 and was administered before chemotherapy cycles 2, 4, and 6 for objective 2. p53 level in peripheral lymphocytes was measured on day 1 of each cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for the subsequent cycles of 2, 4, and 6 respectively. If p53 level for the subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined as "suppressed" (or "activated") for the pair of cycles. Repeated measures linear models of CBC in terms of day, cycle, p53 activity and interaction terms were used. Twenty-six patients treated with 3 week cycle regimens form the base of analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts were significantly higher in the "suppressed" relative to the "activated" group. These data support the proof of principle that suppression of p53 could lead to protection of bone marrow in patients receiving chemotherapy. This trial is registered in ClinicalTrials.gov. Identifier: NCT01428128.

Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer.

Purpose: Several isotopes are available for low dose‐ratebrachytherapy of the prostate. Currently, most implants use a single isotope. However, the use of dual‐isotope implants may yield an advantageous combination of characteristics such as half‐life and relative biological effectiveness. However, the use of dual‐isotope implants complicates treatment planning and quality assurance. Do the benefits of dual‐isotope implants outweigh the added difficulty? The goal of this work was to use a linear‐quadratic model to compare single and dual‐isotope implants. Methods: Ten patients were evaluated in this study. For each patient, six treatment plans were created with single or dual‐isotope combinations of 1251, 103Pd and 131Cs. For each plan the prostate, urethra, rectum and bladder were contoured by a physician. The biologically effective dose was used to determine the tumor control probability and normal tissue complication probabilities for each plan. Each plan was evaluated using favorable, intermediate and unfavorable radiobiological parameters. The results of the radiobiological analysis were used to compare the single and dual‐isotope treatment plans. Results: Iodine‐125 only implants were seen to be most affected by changes in tumor aggressiveness. Significant differences in organ response probabilities were seen at common dose levels. It was recognized that these differences were likely a result of suboptimal initial seed strengths. After adjusting the initial seed strength to maximize complication‐free tumor control the differences between isotope combinations were minimal. This result was true even for unfavorable tumors.Conclusions: The objective of this work was to perform a radiobiologically based comparison of single and dual‐isotope prostate seed implant plans. For all isotope combinations, the plans were improved by varying the initial seed strength. For the minimally‐optimized treatment plans, no substantial differences in predicted treatment outcomes were seen among the different isotope combinations.

The purpose of this study is to evaluate the clinical efficacy of both step-and-shoot IMRT and 3D-Conformal Radiation Therapy modalities (CRT) in treating prostate cancer using radiobiological measures. Another aim was to estimate the risks for developing secondary malignancies in bladder and rectum due to radiotherapy from the corresponding modalities. The treatment plans of ten prostate cancer patients were developed using IMRT and CRT. For the IMRT plans, two beam energies and two treatment protocols were used (the RTOG 0415 and a most restrictive one proposed by Fox Chase Cancer Center (FCCC)). For the evaluation of these plans, the complication-free tumor control probability, the total probability of injury, the total probability of control/benefit, and the biologically effective uniform dose were employed. Furthermore, based on the dosimetric data of IMRT and CRT, the risk for secondary malignancies was calculated for bladder and rectum. The average risk for secondary malignancy was lower for the bladder (0.37%) compared to the rectum (0.81%) based on all the treatment plans of the ten prostate cancer patients. The highest average risk for secondary malignancy for bladder and rectum was for the CRT-6X modality (0.46% and 1.12%, respectively) and the lowest was for the IMRT RTOG-18X modality (0.33% and 0.56%, respectively). The ≥ Grade 2 LENT/SOMA response probability was lower for the bladder than for the rectum in all the plans. For the bladder the highest average value was for the IMRT RTOG-18X (0.9%) and the lowest was for the CRT-18X modality (0.1%). For the rectum, the highest average value was for the IMRT RTOG-6X (11.9%) and the lowest was for the IMRT FCCC-18X modality (2.2%). By using radiobiological measures it is shown that the IMRT FCCC plans had the lowest risks for normal tissue complications, whereas the IMRT RTOG had the highest. Regarding the risk for secondary malignancies, the CRT plans showed the highest values for both bladder and rectum.

BACKGROUND Surveillance and focal therapy are increasingly considered for low risk prostate cancer (PC). We describe pathological characteristics of low risk PC at radical prostatectomy in contemporary patients.

Aim To identify risk factors for locoregional relapse after radical nephrectomy for renal cell carcinoma. Methods We retrospectively reviewed the charts of 259 patients who underwent radical nephrectomy for sporadic clinically localized unilateral renal cell carcinoma between 1998 and 2012. Relapse patterns (locoregional and/or distant) were identified. Relapse-free survival was calculated using Kaplan–Meier method. Factors associated with decreased relapse-free survival were identified using univariate and multivariate Cox proportional hazards regression model analysis. Locoregional relapse estimates were calculated for individual factors and combination of factors. Results At a median follow-up of 68 months (interquartile range: 75 months), 24% patients relapsed. Of these, 54% had locoregional relapse. High-grade, positive margin, large tumor size and stage III/IV were associated with worse relapse-free survival on multivariate analysis. Locoregional relapse occurred among patients with tumor size >7– 10 cm (35%), stage III/IV (31%), grade III/IV (26%), renal vein invasion (22%), perinephric fat invasion (30%), 7 cm plus grade I/II (21%), >7 cm plus grade III/IV (48%), stage III/IV plus grade I/II (24%) and stage III/IV plus grade III/IV (45%). Conclusion We were able to discern risk factors (individual or in combination) associated with increased risk of locoregional relapse after radical nephrectomy for renal cell carcinoma. This could help distinguish patients who may benefit from adjuvant locoregionally directed therapy.

An overall intent of radiotherapy is to precisely target tumor cells, while minimizing exposures to surrounding normal tissue. Despite successes, there is growing concern that an unacceptably large volume of normal tissue is unavoidably exposed. Chromosome aberrations provide a direct measure of ionizing radiation (IR)-induced DNA damage, as well as an indirect measure of future risk since they are associated with virtually all known cancers. Such structural variants (SVs) include translocations (rearrangements between chromosomes) and inversions (rearrangements within chromosomes), the latter being recently identified as part of a distinctive mutational signature associated with radiation therapy-induced second malignancies. Directional Genomic Hybridization (dGH), is a strand-specific cytogenomics-based methodology for cell-by-cell, high-resolution detection of all SVs, particularly inversions, which when combined with compatible subtelomere probes (Telo-dGH), can be used to distinguish inversions from recombination events (sister chromatid exchange) involving chromosomal termini. Telomeres are critical structural elements that serve to protect the physical ends of chromosomes. Dysfunctional telomeres are associated with instability and carcinogenesis, as well as with a variety of other age-related pathologies (e.g., cardiovascular disease). We are validating Telo-dGH as a prospective “personalized” approach of evaluating normal tissue injury, and therefore future risk, associated with radiation therapy - regardless of tumor type or treatment modality. Here, we report results of monitoring prostate cancer patients before and after intensity-modulated radiation therapy (IMRT) to assess radiosensitivity (toxicity), as well as risk of secondary malignancy and other degenerative late effects. Such a strategy has the potential to better inform patient treatment and management decisions based on predicted individual risk. Citation Format: Jared J. Luxton, Miles J. McKenna, Lynn Taylor, Gregory P. Swanson, Susan M. Bailey. Chromosomal and telomeric biomarkers of normal tissue injury to evaluate risk of secondary malignancy following IMRT for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4869.

Importance Hypofractionated radiotherapy (HRT) would be more convenient for men with low-risk prostate cancer and cost less than conventional radiotherapy (CRT) as long as HRT is noninferior to CRT in terms of survival and quality of life (QOL) is not found to be worse. Objective To assess differences in QOL between men with low-risk prostate cancer who are treated with HRT vs CRT. Design, Setting, and Participants In this phase 3 randomized clinical trial, men with low-risk prostate cancer were enrolled from sites within the National Cancer Institute’s National Clinical Trials Network in the United States, Canada, and Switzerland. Interventions Random assignment to CRT (73.8 Gy in 41 fractions over 8.2 weeks) or to HRT (70 Gy in 28 fractions over 5.6 weeks). Main Outcomes and Measures Quality of life was assessed using the Expanded Prostate Index Composite questionnaire measuring bowel, urinary, sexual, and hormonal domains; the 25-item Hopkins Symptom Checklist measuring anxiety and depression; and the EuroQol–5 Dimension questionnaire measuring global QOL. All data were collected at baseline and 6, 12, 24, and 60 months. Change scores were compared between treatment arms using the Wilcoxon signed rank test. A significance level of .0125 to adjust for multiple comparisons was used for an overall 2-sided type 1 error of .05. Clinical significance was determined for the Expanded Prostate Index Composite change scores by an effect size of 0.5. Results Of 1092 patients analyzable for the primary end point, 962 (mean [SD] age, 66.6 [7.4] years) consented to the QOL component. No statistically significant differences with regard to baseline characteristics nor any of the QOL baseline domains were measured between arms. There were no differences in change score between arms with respect to any of the Expanded Prostate Index Composite questionnaire domain scores except at 12 months when the HRT arm had a larger decline than the CRT arm in the bowel domain (mean score, −7.5 vs −3.7, respectively;P Conclusions and Relevance Treatment with HRT is noninferior to CRT in men with low-risk prostate cancer in terms of disease-free survival and, as shown in the present study, in prostate cancer–specific (eg, bowel, bladder, sexual) and general QOL, as well as in anxiety and depression. This study provides evidence to affirm that HRT is a practice standard for men with low-risk prostate cancer. Trial Registration ClinicalTrials.gov identifier:NCT00331773

Surgery is one of the most common curative modalities in prostate cancer. Unfortunately, as with any therapy, patients can suffer recurrence. Postoperative adjuvant therapy has been shown to prevent or delay recurrence. The presence of positive margins puts the patient at a high risk for recurrence. Additional risk factors have been identified that can predict for recurrence, but it is still uncertain as to who warrants immediate treatment. We reviewed the extensive surgical literature for prognostic factors for recurrence in addition to positive margins. We attempted to be exhaustive, first searching PubMed and Medline for all papers for radical prostatectomy and then checking the articles cited in those papers. We sought out papers that reviewed the effect of positive margins and its modifying factors on outcome. With the supposition that patients with >70% risk of failure is enough to consider additional treatment, we were able to identify the factors that appear to consistently place patients at or above that level of recurrence. For patients with positive margins, any one of these factors places the patients at a very high risk of recurrence: positive lymph nodes or seminal vesicles, preoperative PSA > 20 ng/ml, or a Gleason score > 7. Many Gleason 7 patients with positive margins fall into the >70% risk of failure category, especially if they have additional risk factors (i.e., those with extraprostatic extension). While there are no absolutes, all these patients should be strongly considered for adjuvant therapy in addition to radical prostatectomy.

Purpose We aimed to validate a previously described genetic risk score, denoted the cell-cycle progression (CCP) score, in predicting contemporary radical prostatectomy (RP) outcomes. Methods RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. Recurrence was defined as two prostate-specific antigen levels ≥ 0.2 ng/mL or any salvage treatment. Associations between CCP score and recurrence were examined, with adjustment for clinical and pathologic variables using Cox proportional hazards regression and partial likelihood ratio tests. The CCP score was assessed for independent prognostic utility beyond a standard postoperative risk assessment (Cancer of the Prostate Risk Assessment post-Surgical [CAPRA-S] score), and a score combining CAPRA-S and CCP was validated. Results Eighty-two (19.9%) of 413 men experienced recurrence. The hazard ratio (HR) for each unit increase in CCP score (range, −1.62 to 2.16) was 2.1 (95% CI, 1.6 to 2.9); with adjustment for CAPRA-S, the HR was 1.7 (95% CI, 1.3 to 2.4). The score was able to substratify patients with low clinical risk as defined by CAPRA-S ≤ 2 (HR, 2.3; 95% CI, 1.4 to 3.7). Combining the CCP and CAPRA-S improved the concordance index for both the overall cohort and low-risk subset; the combined CAPRA-S + CCP score consistently predicted outcomes across the range of clinical risk. This combined score outperformed both individual scores on decision curve analysis. Conclusion The CCP score was validated to have significant prognostic accuracy after controlling for all available clinical and pathologic data. The score may improve accuracy of risk stratification for men with clinically localized prostate cancer, including those with low-risk disease.