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Background Patients with prostate cancer suffer significant sexual dysfunction after treatment which negatively affects them and their partners psychologically, and strain their relationships. Aim We convened an international panel with the aim of developing guidelines that will inform clinicians, patients and partners about the impact of prostate cancer therapies (PCT) on patients’ and partners’ sexual health, their relationships, and about biopsychosocial rehabilitation in prostate cancer (PC) survivorship. Methods The guidelines panel included international expert researchers and clinicians, and a guideline methodologist. A systematic review of the literature, using the Ovid MEDLINE, Scopus, CINAHL, PsychINFO, LGBT Life, and Embase databases was conducted (1995–2022) according to the Cochrane Handbook for Systematic Reviews of Interventions. Study selection was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Each statement was assigned an evidence strength (A-C) and a recommendation level (strong, moderate, conditional) based on benefit/risk assessment. Data synthesis included meta-analyses of studies deemed of sufficient quality (3), using A Measurement Tool to Assess Systematic Reviews (AMSTAR). Outcomes Guidelines for sexual health care for patients with prostate cancer were developed, based on available evidence and the expertise of the international panel. Results The guidelines account for patients’ cultural, ethnic, and racial diversity. They attend to the unique needs of individuals with diverse sexual orientations and gender identities. The guidelines are based on literature review, a theoretical model of sexual recovery after PCT, and 6 principles that promote clinician-initiated discussion of realistic expectations of sexual outcomes and mitigation of sexual side-effects through biopsychosocial rehabilitation. Forty-seven statements address the psychosexual, relationship, and functional domains in addition to statements on lifestyle modification, assessment, provider education, and systemic challenges to providing sexual health care in PC survivorship. Clinical Implications The guidelines provide clinicians with a comprehensive approach to sexual health care for patients with prostate cancer. Strengths & Limitations The strength of the study is the comprehensive evaluation of existing evidence on sexual dysfunction and rehabilitation in prostate cancer that can, along with available expert knowledge, best undergird clinical practice. Limitation is the variation in the evidence supporting interventions and the lack of research on issues facing patients with prostate cancer in low and middle-income countries. Conclusion The guidelines document the distressing sexual sequelae of PCT, provide evidence-based recommendations for sexual rehabilitation and outline areas for future research.

BackgroundProstatic radiation therapy (RT) leads to erectile dysfunction by damaging peri-prostatic pro-erectile nerves of the pelvic ganglion. Schwann cells (SC) facilitate neuronal repair after mechanical injury, however, their role in repair of pelvic neurons post-radiation hasn’t been explored.AimTo determine if SCs cocultured with primary pelvic neurons can rescue neuronal survival and growth after ex vivo RT.MethodsMajor pelvic ganglia (MPG) were collected from adult male Sprague-Dawley rats (n = 12) to isolate SCs. SCs received RT (0 or 8 Gy), were plated on coated coverslips and grown to confluence before the addition of neurons. Additional MPGs were irradiated (0 or 8 Gy) and digested to isolate pelvic neurons. Dissociated neurons were plated alone or atop SC-coated coverslips to create 6 experimental groups (n = 3/grp): (i) Control (CON) MPG, (ii) RT MPG, (iii) CON SC + CON MPG, (iv) CONSC + RT MPG, (v) RT SC + CON MPG, and (iv) RT SC + RT MPG. After 72 hours, coverslips were fixed and stained for beta-tubulin (neuron marker), S100 (SC marker), neuronal nitric oxide synthase (nitrergic marker), tyrosine hydroxylase (sympathetic marker), and terminal deoxynucleotidyl transferase dUTP nick-end labeling.OutcomesWe measured neurite length, branching, specific neuron populations and apoptosis.ResultsEx vivo RT decreased MPG neuron length, increased apoptosis and decreased nitrergic neurons in monoculture. Compared to all other groups, CON SC + RT MPG cocultures demonstrated increased neurite outgrowth (P < .001). Neurite branching was decreased in the RT MPG + RT SC coculture, but unchanged in other cocultures. Groups containing RT MPG neurons exhibited increased apoptosis, but coculture with CON SC reduced the degree of RT-induced apoptosis (P < .01). The number of tyrosine hydroxylase positive neurons was unchanged while nitrergic neurons were significantly lower in RT neurons and coculture with CON SCs was unable to prevent nitrergic loss.Clinical TranslationThese findings suggest that SCs may be an important target in prostate cancer patients with radiation-induced pelvic neuropathy to promote MPG neuron survival and neuronal repair after RT.Strengths and LimitationsThis is the first study to characterize the ex vivo ability of SCs to rescue pelvic nerve growth and survival. The study is limited by little supporting mechanistic molecular data and the need to confirm the ability of healthy SCs to promote pelvic neuron survival and repair following prostatic RT in vivo.ConclusionUnirradiated SCs partially mitigated RT-induced MPG apoptosis but did not affect the loss of nitrergic neuron populations suggesting that SCs promote irradiated MPG neuron survival and facilitate intrinsic repair functions.

PURPOSE Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities. METHODS Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t-tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t-test. RESULTS Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups. CONCLUSION Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors.

Cancer survivors are often sedentary. Self-monitoring may promote physical activity through self-activation. We conducted a pilot trial to evaluate whether wearable activity tracker with personalized text message feedback would increase physical activity. We enrolled 30 patients with solid tumor cancers into a non-randomized prospective intervention trial (NCT02627079): 15 had completed treatment in the past year and 15 under active treatment. Each participant received an activity tracker and daily text messages personalized to their activity level. We assessed patient-reported outcomes and 6-min walk (6 MW) at baseline and 3 months. Twenty-six participants completed the study. There was substantial variation in baseline activity. Overall, 39% of participants increased their steps taken by at least 20%, and 23% increased their 6 MW distance by 20% or more. More participants who had completed treatment strongly agreed (73%) that the intervention increased their exercise levels than those receiving active treatment (47%). At 3 months, there was a significant improvement in median Beck Depression Inventory-II and Godin Leisure Index composite scores. At 6 months, 72% still wore their activity tracker at least 4 days per week. We found that the intervention was well-accepted with a high completion rate at 3 months and continued self-use at 6 months. In this pilot study of combined activity tracker and motivational messaging, we found a signal for increased physical activity over a 3-month period. Future research is needed to study this technique for its impact on activity and other physical and psychological measures of well-being. Activity tracker with personalized motivational messaging may be useful in promoting physical activity in cancer survivors.

AIMS To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats. METHODS Male Sprague-Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2- and 10-weeks post-RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha-smooth muscle actin. MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy-terminal hydrolase L1 (Uchl1) and Chat. RESULTS At 2 weeks post-RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p

Purpose Oligorecurrent prostate cancer has historically been treated with indefinite androgen deprivation therapy (ADT), although many patients and providers opt to defer this treatment at the time of recurrence given quality-of-life and/or comorbidity considerations. Recently, metastasis-directed therapy (MDT) has emerged as a potential intermediary between surveillance and immediate continuous ADT. Simultaneously, advanced systemic therapy in addition to ADT has also been shown to improve survival in metastatic hormone-sensitive disease. This study aimed to compare the cost-effectiveness of treating oligorecurrent patients with upfront MDT before standard-of-care systemic therapy. Methods and Materials A Markov-based cost-effectiveness analysis was constructed comparing 3 strategies: (1) upfront MDT → salvage abiraterone acetate plus prednisone (AAP) + ADT → salvage docetaxel + ADT; (2) upfront AAP + ADT → salvage docetaxel + ADT; and (3) upfront docetaxel + ADT → salvage AAP + ADT. Transition probabilities and utilities were derived from the literature. Using a 10-year time horizon and willingness-to-pay threshold of $100,000/quality-adjusted life year (QALY), net monetary benefit values were subsequently calculated for each treatment strategy. Results At 10 years, the base case revealed a total cost of $141,148, $166,807, and $136,154 with QALYs of 4.63, 4.89, and 4.00, respectively, reflecting a net monetary benefit of $322,240, $322,018, and $263,407 for upfront MDT, upfront AAP + ADT, and upfront docetaxel + ADT, respectively. In the probabilistic sensitivity analysis using a Monte Carlo simulation (1,000,000 simulations), upfront MDT was the cost-effective strategy in 53.6% of simulations. The probabilistic sensitivity analysis revealed 95% confidence intervals for cost ($75,914-$179,862, $124,431-$223,892, and $103,298-$180,617) and utility in QALYs (3.85-6.12, 3.91-5.86, and 3.02-5.22) for upfront MDT, upfront AAP + ADT, and upfront docetaxel + ADT, respectively. Conclusions At 10 years, upfront MDT followed by salvage AAP + ADT, is comparably cost-effective compared with upfront standard-of-care systemic therapy and may be considered a viable treatment strategy, especially in patients wishing to defer systemic therapy for quality-of-life or comorbidity concerns. Additional studies are needed to determine whether MDT causes a sustained meaningful delay in disease natural history and whether any benefit exists in combining MDT with upfront advanced systemic therapy.

To examine the feasibility of an enhanced survivorship care plan (ESCP) that integrated the web-based program Patient Education Resources for Couples (PERC) into a standardized survivorship care plan (SCP) and estimated the outcomes of ESCPs versus SCPs. In this randomized pilot trial, localized prostate cancer (PC) patients and partners (i.e., couple) were randomly assigned to ESCP that contained a link to PERC or to SCP that contained a link to general PC information on the National Cancer Institute website. Couples completed assessments measuring quality of life (QOL), appraisal of symptoms, and coping resources at baseline (T1) and 4–6 months later (T2). We examined feasibility (e.g., recruitment and retention) using descriptive statistics. Linear mixed models examined changes in couples’ outcomes over time and Poisson regression examined differences in patient healthcare utilization. Sixty-two couples completed T1 surveys (recruitment rate 41.6%) and were randomly assigned to receive ESCP (n = 31) or SCP (n = 31). Twenty-eight (ESCP) and 25 (SCP) couples completed T2 surveys (retention rates = 90.3% vs. 80.7%). ESCP participants (70%) reviewed webpages consistent with patients’ symptoms. ESCP patients reported greater program satisfaction (p = 0.02) and better urinary symptom scores (p

Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED. A systematic review of the literature published between January 2002 and December 2018 was performed to obtain patient reported rates of ED after definitive external beam radiotherapy, ultrafractionated stereotactic radiotherapy, and brachytherapy (BT) to the prostate in men who were potent prior to RT. Univariate and multivariate analyses of radiation dose, treatment strategy, and length of follow-up were analyzed to ascertain their relationship with RT-induced ED. Of 890 articles reviewed, 24 met inclusion criteria, providing data from 2714 patients. Diminished erectile function status post RT was common and similar across all studies. The median increase in men reporting ED was 17%, 26%, 23%, and 23%, 3DCRT, IMRT, low dose rate BT, and SBRT, respectively, at 2-year median follow-up. ED is a common side effect of RT. Risk of post-RT ED is similar for both LDR brachytherapy and external beam RT with advanced prostate targeting and penile-bulb sparing techniques utilized in modern RT techniques.

Background Prostatic radiation therapy (RT) often causes erectile dysfunction (ED) and the mechanisms governing RT-induced ED are unclear with a lack of therapeutic strategies. Aim To determine the effects of ex vivo RT on major pelvic ganglion (MPG) neuron survival, and neurite growth in whole vs dissociated culture. Methods MPGs were removed and irradiated (0 or 8 Gy) from male Sprague Dawley rats. For dissociated culture, MPG neurons were digested in collagenase/dispase and cultured on coverslips. Immunofluorescent staining for beta-tubulin III (TUBB3; neuron marker), neuronal nitric oxide synthase (nNOS; nitrergic marker), tyrosine hydroxylase (TH; sympathetic marker), and terminal deoxynucleotidyl transferase dUTP nick end labeling assessed neurite length, branching, autonomic neuron density, and apoptosis. For whole organ culture, MPGs were grown in Matrigel. Gene expression of apoptotic markers (caspase 1, 3), TUBB3, nNOS, TH, and Schwann cells (Sox10, Krox20, glial fibrillary acid protein) was measured in whole organ cultured MPGs by quantitative polymerase chain reaction. Outcomes After 72 hours, neurite length, branching, autonomic neuron density, and apoptosis were assessed, and gene expression was measured. Results RT increased apoptosis in dissociated neurons measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (P Clinical Translation Prostatic RT leads to increased neuronal cell death and less erectogenic nitrergic neurons contributing to ED. Strengths & Limitations The advantages of dissociated neuron culture include distinct neurites which are easily measured for apoptosis, length/branching, and specific neuron types. In contrast, whole MPG culture is advantageous as it contains all the supporting cells present in vivo. Conclusion The 2 different culture methods demonstrated opposing neurite growth after RT indicating the importance of supporting cell network to promote pelvic neuron neuritogenesis and survival following RT.

TPS283 Background: There is no clear standard of care for biochemically recurrent prostate cancer (PCa) with positron emission tomography (PET)-detected oligometastases and normal conventional imaging (CIM). Phase II trials show that stereotactic ablative body radiotherapy (SABR) to oligometastases may delay cancer progression and initiation of androgen deprivation therapy (ADT) and its untoward effects. ADT with radiation prolongs survival in locally advanced PCa and in CIM metastatic PCa. However, there is a knowledge gap about timing and benefit vs toxicity of ADT with SABR in early oligometastatic PCa. NRG GU011 (PROMETHEAN) is a randomized phase II trial of SABR with or without relugolix for early PET-detected recurrent oligometastatic PCa. This study aims to evaluate the impact of relugolix, a novel oral gonadotropin-releasing hormone receptor antagonist, when combined with SABR to oligometastases. Relugolix allows for rapid testosterone recovery and is associated with fewer cardiovascular events when compared to leuprolide and is hypothesized to have low late ADT toxicity. GU011 will provide patients and their physicians data on the relative risks and benefits of early or delayed ADT in this setting. Methods: NRG-GU011 NCT# 05053152 is a randomized phase II double-blinded, placebo-controlled trial with randomization to SABR + 6 months placebo vs SABR + 6 months relugolix. Eligible patients have biochemical recurrence after prior curative intent radiation or surgery for localized PCa, PSA < 10 ng/mL, negative CIM and 1-5 PET-evident metastases (≥1 extrapelvic). SABR is delivered in 1-5 fractions to BED >100 Gy1.5, followed by placebo or relugolix 120mg daily for 6 months. Patients will then be followed with imaging at time of biochemical recurrence. The planned sample size of 260 patients (130 per arm) will provide 85% power to detect a hazard ratio of 0.65 for radiographic progression-free survival (rPFS), based on a one-sided test at alpha 0.10. Planned enrollment is predicted at 8 patients per month with an estimated study completion date of late 2026. The primary endpoint is CIM rPFS. Secondary endpoints include PET-based rPFS, sexual and hormonal quality of life (QoL) assessed by EPIC-26, other QoL measures from EQ5D-5L, EORTC QLQ-30 and PROMIS Fatigue, and between-group comparisons of time to salvage therapy, castration-resistance, local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival. We also aim to determine adverse event rates for both treatment arms and evaluate genomic and blood markers of treatment response. This study opened in December 2021. Clinical trial information: NCT05053152 .

Despite significant sexual dysfunction and distress after localized prostate cancer treatment, patients typically receive only physiologic erectile dysfunction management. The authors performed a randomized controlled trial of an online intervention supporting couples' posttreatment recovery of sexual intimacy.Patients treated with surgery, radiation, or combined radiation and androgen deprivation therapy who had partners were recruited and randomized to an online intervention or a control group. The intervention, tailored to treatment type and sexual orientation, comprised 6 modules addressing expectations for sexual and emotional sequelae of treatment, rehabilitation, and guidance toward sexual intimacy recovery. Couples, recruited from 6 sites nationally, completed validated measures at the baseline and 3 and 6 months after treatment. Primary outcome group differences were assessed with t tests for individual outcomes.Among 142 randomized couples, 105 patients (mostly surgery) and 87 partners completed the 6-month survey; this reflected challenges with recruitment and attrition. There were no differences between the intervention and control arms in Patient-Reported Outcomes Measurement Information System Global Satisfaction With Sex Life scores 6 months after treatment (the primary outcome). Three months after treatment, intervention patients and partners reported more engagement in penetrative and nonpenetrative sexual activities than controls. More than 73% of the intervention participants reported high or moderate satisfaction with module content; more than 85% would recommend the intervention to other couples.Online psychosexual support for couples can help couples to connect and experience sexual pleasure early after treatment despite patients' sexual dysfunction. Participants' high endorsement of the intervention reflects the importance of sexual health support to couples after prostate cancer treatment.This study tested a web-based program supporting couples' sexual recovery of sexual intimacy after prostate cancer treatment. One hundred forty-two couples were recruited and randomly assigned to the program (n = 60) or to a control group (n = 82). The program did not result in improvements in participants' satisfaction with their sex life 6 months after treatment, but couples in the intervention group engaged in sexual activity sooner after treatment than couples in the control group. Couples evaluated the program positively and would recommend it to others facing prostate cancer treatment.

Background Erectile dysfunction (ED) is the most common side effect of prostate radiotherapy (RT), but reported rates over time and across modalities have varied widely. Aim To evaluate the published literature between 2002 and 2018 for high quality data utilizing prospectively gathered patient-reported ED, and to summarize the challenges in reporting of RT-induced ED (RIED). Methods A PubMed search and literature review was performed to identify articles describing rates of ED before and after definitive external beam RT or brachytherapy without androgen deprivation. Outcomes Patient-reported ED, patient and treatment variables, and study follow-up constituted the main outcomes of this study. Results 24 articles were identified, reporting RIED rates between 17% and 90%. Variables contributing to this range included patient, treatment, and study characteristics known to impact ED reporting. Clinical Implications For future studies, we recommend the use of validated patient-reported questionnaires and reporting of baseline function and comorbidities, RT type and dose, and use of androgen deprivation therapy and erectile aids at the time of ED measurement. With sufficient follow-up to understand the late nature of RIED, these recommendations will improve comparison of results between studies and the applicability of results to patients undergoing pretreatment counseling regarding the risks of RIED. Strengths & Limitations The literature search and formulation of results were based on a broad understanding of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and the literature, but because of the focus on data reporting, a comprehensive systematic review of all RIED literature was not performed. Conclusion Reported rates of ED after RT vary widely due to differences in patients' baseline reported erectile function, age, comorbidities, and characteristics of the treatment delivered. The methodology of ED measurement has significant impact on the applicability and comparability of results to other studies and clinical practice.

Context Radiotherapy used for treating localized prostate cancer is effective at prolonging cancer-specific and overall survival. Still, acute and late pelvic toxicities are a concern, with gastrointestinal (GI) and genitourinary (GU) sequelae being most common as well as other pelvic complications. Objective To present a critical review of the literature regarding the incidence and risk factors of pelvic toxicity following primary radiotherapy for prostate cancer and to provide a narrative review regarding its management. Evidence acquisition A collaborative narrative review of the literature from 2010 to present was conducted. Evidence synthesis Regardless of the modality used, the incidence of acute high-grade pelvic toxicity is low following conventionally fractionated external beam radiotherapy (EBRT). After moderate hypofractionation, the crude cumulative incidences for late grade 3 or higher (G3+) GI and GU complications are as high as 6% and 7%, respectively. After extreme hypofractionation, the 5-yr incidences of G2+ GU and GI toxicities are 3–9% and 0–4%, respectively. Following brachytherapy monotherapy, crude rates of late G3+ GU toxicity range from 6% to 8%, while late GI toxicity is rare. With combination therapy (EBRT and brachytherapy), the cumulative incidence of late GU toxicity is high, between 18% and 31%; however, the prevalence is lower at 4–14%. Whole pelvic radiotherapy remains a controversial treatment option as there is increased G3+ GI toxicity compared with prostate-only treatment, with no overall survival benefit. Proton beam therapy appears to have similar toxicity to photon therapies currently in use. With respect to specific complications, urinary obstruction and urethral stricture are the most common severe urinary toxicities. Rectal and urinary bleeding can be recurrent long-term toxicities. The risk of hip fracture is also increased following prostate radiotherapy. The literature is mixed on the risk of in-field secondary pelvic malignancies following prostate radiotherapy. Urinary and GI fistulas are rare complications. Management of these toxicities may require invasive treatment and reconstructive surgery for refractory and severe symptoms. Conclusions There has been progress in the delivery of radiotherapy, enabling the administration of higher doses with minimal tradeoff in terms of slightly increased or equal toxicity. There is a need to focus future improvements in radiotherapy on sparing critical structures to reduce GU and GI morbidities. While complications such as fistulae, bone toxicity, and secondary malignancy are rare, there is a need for higher-quality studies assessing these outcomes and their management. Patient summary In this report, we review the literature regarding pelvic complications following modern primary prostate cancer radiotherapy and their management. Modern radiotherapy technologies have enabled the administration of higher doses with minimal increases in toxicity. Overall, high-grade long-term toxicity following prostate radiotherapy is uncommon. Management of late high-grade pelvic toxicities can be challenging, with patients often requiring invasive therapies for refractory cases.

One of the most common side effects of urologic cancer and its treatment is sexual dysfunction. This negative consequence can occur because of changes in anatomy and/or the physiologic response to sexual stimuli, but also due to the psychological impact of those physical changes and the cancer experience. Sexual health is a key part of survivorship, but it is under-emphasized in training and can be overlooked in clinical practice. To support the sexual health of the urologic cancer survivor, the urologic oncologist should: 1) acknowledge and educate the patient about the potential effects, 2) be sensitive to identifying sexual issues as they arise, and 3) be aware of treatment strategies and be able to access the team members needed to provide these strategies. As sexual function requires a complex interplay of anatomy, physiology, and psychology, so does addressing sexual dysfunction resulting from cancer treatment. In this special Seminars issue, we review the sexual dysfunction consequences of urologic cancers in both men and women and strategies to maximize sexual health.

The management of urothelial recurrences following trimodal therapy (TMT) for bladder cancer is dependent on the nature and location of the recurrence – non-muscle-invasive or muscle-invasive, versus upper tract or urethral. Non-muscle-invasive recurrences can be managed similarly to how any recurrent non-muscle-invasive urothelial carcinoma is managed. It requires transurethral resection of the bladder tumor to provide accurate staging and completely resect the recurrence. Intravesical therapy has been described in these patients following TMT. In available studies, almost 20% of patients progressed to muscle-invasive disease. Muscle-invasive recurrences should be managed with radical cystectomy if patient desires a curative management plan. Despite historic concerns regarding operating in an irradiated pelvis, salvage radical cystectomy can safely be performed in post-TMT patients and survival outcomes appear similar to those for radical cystectomy as primary management of muscle-invasive urothelial carcinoma. There are limited data regarding upper tract recurrences following TMT, but they can generally be managed similarly to those occurring in non-irradiated bladder. Similarly, data on urethral recurrence following TMT are sparse and clinicians can follow current guidelines for its management. The only role for additional radiation in the post-TMT patient is a palliative one, for intractable hematuria or pelvic pain.

Treatment planning for prostate volumetric modulated arc therapy (VMAT) can take 5–30 min per plan to optimize and calculate, limiting the number of plan options that can be explored before the final plan decision. Inspired by the speed and accuracy of modern machine learning models, such as residual networks, we hypothesized that it was possible to use a machine learning model to bypass the time-intensive dose optimization and dose calculation steps, arriving directly at an estimate of the resulting dose distribution for use in multi-criteria optimization (MCO). In this study, we present a novel machine learning model for predicting the dose distribution for a given patient with a given set of optimization priorities. Our model innovates upon the existing machine learning techniques by utilizing optimization priorities and our understanding of dose map shapes to initialize the dose distribution before dose refinement via a voxel-wise residual network. Each block of the residual network individually updates the initialized dose map before passing to the next block. Our model also utilizes contiguous and atrous patch sampling to effectively increase the receptive fields of each layer in the residual network, decreasing its number of layers, increasing model prediction and training speed, and discouraging overfitting without compromising on the accuracy. For analysis, 100 prostate VMAT cases were used to train and test the model. The model was evaluated by the training and testing errors produced by 50 iterations of 10-fold cross-validation, with 100 cases randomly shuffled into the subsets at each iteration. The error of the model is modest for this data, with average dose map root-mean-square errors (RMSEs) of 2.38 ± 0.47% of prescription dose overall patients and all optimization priority combinations in the patient testing sets. The model was also evaluated at iteratively smaller training set sizes, suggesting that the model requires between 60 and 90 patients for optimal performance. This model may be used for quickly estimating the Pareto set of feasible dose objectives, which may directly accelerate the treatment planning process and indirectly improve final plan quality by allowing more time for plan refinement.

Long-term androgen-deprivation therapy (ADT) is the standard of care in combination with radiation therapy (RT) in high-risk prostate cancer (PC), despite substantial toxicity from the resulting hypogonadism. We hypothesized that a combination of more potent but shorter-term androgen inhibition in men with intermediate- or high-risk localized PC would synergize with definitive RT to provide short-term testosterone recovery and improve disease control.This prospective phase 2 single-arm trial enrolled men with low-volume unfavorable intermediate or high-risk localized PC. Treatment included 6 months of ADT concurrent with abiraterone acetate plus prednisone (AAP) once daily and RT to prostate and seminal vesicles. The primary endpoint was the proportion of men with an undetectable prostate-specific antigen (PSA) at 12-months; secondary objectives included biochemical progression-free survival (PFS), testosterone recovery, toxicity, and sexual and hormonal quality of life.We enrolled 37 men between January 2014 and August 2016, 45% of whom were high risk. All patients had T1-2 disease and PSA20 ng/mL. Median follow-up is 37 months (95% confidence interval [CI], 35.7-39.1). Treatment noted 32% grade 3 toxicities related to AAP, predominantly hypertension, with no toxicities ≥G4. The rate of undetectable PSA at 12 months was 55% (95% CI, 36%-72%). With 46 months of median follow-up, 2 of 37 patients developed PSA progression (36-month PFS = 96%; 95% CI, 76%-99%), and 81% of patients recovered testosterone with a median time to recovery of 9.2 months. Hormonal or sexual function declined at 6 months with subsequent improvement by 24 months.The combination of RT and 6 months of ADT and AAP demonstrated acceptable toxicity and a high rate of testosterone recovery with restoration of quality of life and excellent disease control in men with low-volume, intermediate- or high-risk localized prostate cancer. Prospective comparative studies are justified.

Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED.A systematic review of the literature published between January 2002 and December 2018 was performed to obtain patient reported rates of ED after definitive external beam radiotherapy, ultrafractionated stereotactic radiotherapy, and brachytherapy (BT) to the prostate in men who were potent prior to RT. Univariate and multivariate analyses of radiation dose, treatment strategy, and length of follow-up were analyzed to ascertain their relationship with RT-induced ED.Of 890 articles reviewed, 24 met inclusion criteria, providing data from 2714 patients. Diminished erectile function status post RT was common and similar across all studies. The median increase in men reporting ED was 17%, 26%, 23%, and 23%, 3DCRT, IMRT, low dose rate BT, and SBRT, respectively, at 2-year median follow-up.ED is a common side effect of RT. Risk of post-RT ED is similar for both LDR brachytherapy and external beam RT with advanced prostate targeting and penile-bulb sparing techniques utilized in modern RT techniques.

International audience; Two randomized studies of symptom monitoring during chemotherapy or during second line treatment and follow-up via web-based patient-reported outcomes (PROs) was previously demonstrated to lengthen survival. We are presenting here a patient with advanced and recurrent lung cancer who was followed for 4 years by PROs for relapse and adverse events detection. We report how the web-mediated follow-up helped to detect dangerous pulmonary embolism, relapse and pseudo-progression to immunotherapy by self-reported symptom tracking and specific algorithms triggering notifications to medical team, allowing early management of events. We particularly describe how a discordance between objective clinical improvement under immunotherapy assessed by the application allowed to detect pseudo-progression on imaging and allowed maintenance of the treatment during more than 1-year, although imaging report could have led to stop an effective therapy. The progression observed in the routine imaging was indeed in clear contradiction with improvements in patient's global status as assessed by the reduced PRO-score computed from patient self-reported symptoms. The ability of e-health tools based on symptoms reporting for tumor response assessment should be assessed in trials to help physician in decision of stopping or continuing therapy.

Purpose Radiotherapy (RT) is commonly used to treat most pelvic malignancies. While treatment is often effective, curative radiation doses to the rectum can result in chronic radiation-induced proctitis, which is characterized by diarrhea, tenesmus, and/or rectal bleeding, recently termed pelvic radiation disease. An animal model of chronic radiation-induced proctitis would be useful to test both preventative and therapeutic strategies to limit this morbidity but has been elusive because of the high rodent mortality associated with acute bowel RT injury. The objective of this research was to develop a novel mouse model of chronic radiation-induced proctitis using advanced technology. Methods and Materials Using an X-RAD 225-Cx (Precision X-Ray) small animal irradiator, multiple plan configurations were evaluated for planning treatment volume and organ-at-risk avoidance to deliver a 15 Gy 3D conformal treatment plan. The final plan was verified by high resolution 3D dosimetry (PRESAGE/optical-CT), and delivered using a single arc. Mice were monitored for mortality for 250 days, followed by histopathological correlates including mucicarmine, Masson's trichrome, and fecal pellet length. Results Six beam arrangements were considered: single and parallel-opposed fields with whole-pelvis coverage, and collimated fields in parallel-opposed, 3-field, 4-field, and arc geometries. A collimated arc plan offered superior planning treatment volume coverage and organ-at-risk avoidance compared to whole-pelvis irradiation. Treatment verification with PRESAGE 3D dosimetry (Heuris Inc) showed >99% of voxels passing gamma analysis with 2%/2 mm criteria. Our treatment resulted in no acute mortality and 40% mortality at 250 days. Histopathological analysis showed increased mucous production and fibrosis of the irradiated colon, but no change in fecal pellet length. Conclusions Our model was able to target successfully lower colon and rectum with lower mortality than other published models. This permitted measurement of late effects that recapitulate some features of rectal damage in humans.

The biologic effects of changing the daily radiation dose (fractionation) have been studied for more than a century. The fractionation question in the treatment of prostate cancer came into stark relief in 1999 with the publication of a provocative report suggesting that hypofractionated regimens could maintain the therapeutic ratio with logistic and financial advantages. In the last two decades medical evidence, weak and strong, has accumulated on the efficacy and toxicity of hypofractionated regimens in the radiotherapeutic treatment of prostate cancer. This brief review will focus on the results of randomized trials that compare moderate hypofractionation (HF) to conventional fractionation (CF). Extreme HF is covered in a separate review within this issue.

Purpose/objective(s) Telehealth (TH) for radiation oncology services has emerged as a new modality for care delivery and will likely persist beyond the COVID pandemic. Data regarding radiation oncology provider satisfaction of TH are limited and essential to the sustainable adoption of this tool. Materials/methods An anonymous electronic survey assessing TH experience was distributed in 11/2020 to all clinical radiation oncology physicians and APPs at a single large NCI-designated institution, including affiliate clinics. Those who utilized TH (phone or video) were invited to participate. The provider survey was designed using the technology-acceptance model (TAM), a validated method to predict use and acceptance of technology tools. Survey items included 4 assessing provider role, 1 regarding TH utilization, 26 assessing TH experience on a 5-point Likert scale, and 1 free response assessing current barriers to TH. Percent satisfaction is reported as the percentage of top 2 positive or affirmative responses on the Likert scale as a proportion of all responses. Results 19 of 34 radiation oncology providers (56%) completed the survey, including 15 attending physicians and 4 APPs. Providers specialized in central nervous system (n = 3), head and neck (n = 2), gastrointestinal (n = 1), breast (n = 2), genitourinary (n = 4), gynecological (n = 2), sarcoma (n = 1), and general oncology (n = 4). Providers reported having 1-10 (n = 5), 11-15 (n = 7), or > 20 years (n = 7) in practice. Providers utilized TH for on-treatment visits (53%), follow-ups (86%), and consults (79%). 56% of providers enjoyed experimenting with new technology and 61% felt that technological advances improved care for patients. Regarding aspects of the TH clinical encounter: providers had high satisfaction with ability to document the visit (89%), obtaining patient history (83%), and ease of discussing radiation treatment decisions (71%). There was lower satisfaction with ability to create rapport (33%), ease of obtaining consent for radiation (33%), and ease of evaluating physical exam findings (19%). Regarding workflow: 39% felt that TH was compatible with existing oncology clinical workflow, 39% felt TH gave them greater control over work, 33% providers felt that TH improved their job efficiency, and 28% felt TH made them more productive. Regarding ease of TH use: 44% felt that interacting with TH services was frustrating and 39% felt that TH services did not require much training. 24% felt the TH adequately replaced face to face visits. Providers identified the following barriers to TH implementation: lack of MA/RN/APP support, interruptions to TH visits by treatment/simulation clinical duties, lack of dedicated TH template, and burden of navigating the electronic medical record. Conclusion Radiation oncology providers at our institution expressed mixed satisfaction to incorporating TH into their practice. Current strategies to address barriers, including implementation of a telehealth care coordinator, are underway.

Purpose/objective(s) Post-operative radiotherapy (PORT) is utilized in select prostate cancer patients. IMRT has been associated with improved dosimetry and acute toxicity. Smaller treatment margins for PORT have been recommended when using image guidance (IG), which has also been associated with reduced toxicity. Compared to intact prostate IG-IMRT, however, PORT is delivered to a space at risk for recurrence with no grossly visible target, so using targeted conformal techniques with less margin for error may compromise tumor control. Our institution initiated IG-IMRT for PORT in 2005 and adopted larger planning target volumes (PTV) in 2012. We hypothesized that smaller PTV and surgical clip-based IG-IMRT associate with increased biochemical failure (BF). Materials/methods Patients who underwent post-prostatectomy IG-IMRT without concurrent androgen deprivation therapy (ADT) from 1/2005 to 12/2016 were included, with division into pre-2012 and post-2012 cohorts. Demographics and tumor/treatment variables were recorded retrospectively. Oncologic outcomes included BF (initiation of ADT and/or PSA > 0.2 ng/ml and rising) and late toxicities (defined by RTOG criteria, occurring > 90 days after RT). Results 133 patients met criteria: 73 treated pre-2012 and 60 treated post-2012, with a median follow-up of 5 and 9 years, respectively. Compared to the pre-2012 cohort, patients in the post-2012 cohort were more often treated with salvage vs adjuvant RT (P = 0.007), and had higher pre-PORT PSA (0.38 vs 0.20, P = 0.01). 5-year BF did not differ between cohorts (36% vs 43%, P = 0.48). Pre-2012, a smaller percentage of patients underwent on-treatment alignment to surgical clips (40% vs 58%, P = 0.033), vs bony anatomy. Alignment to surgical clips was associated with increased BF in the pre-2012 cohort (HR 2.13, P = 0.041) but not in the post-2012 cohort. Notably, significantly more patients received IG with CBCT in the post-2012 cohort (82% vs 33%). Pre-2012, the median PTV was 198.63 cc versus 242.59 cc post-2012 (P = 0.002). Among the entire cohort on univariate analysis, however, clinical target volume (CTV), CTV-PTV ratio and PTV as continuous variables were not associated with increased risk of BF. Late toxicities were not different between the two cohorts. Conclusion This retrospective analysis reports on toxicity and oncologic outcomes of post-prostatectomy patients treated with IG-IMRT. Despite changes in tumor/treatment characteristics, dosimetric parameters, and image guidance techniques, toxicity and cancer-related outcomes remain similar over a 7-year period. Clip-based IG-IMRT in conjunction with small target volumes may be associated with higher risk of BF, and use of CBCT IG may offset this risk. Additional dosimetric and treatment analyses will be presented. These findings should be validated in prospective datasets.

Purpose/objective(s) Androgen deprivation therapy (ADT) and radiotherapy (RT) are synergistic, and the combination results in improved survival outcomes for aggressive prostate cancers. However, long-term ADT carries substantial burden of toxicity and morbidity. We hypothesized that a combination of definitive prostate RT and short-term complete androgen blockade (CAB) in men with unfavorable intermediate or favorable high-risk localized PC would provide excellent biochemical control and allow high rates of testosterone recovery. This combination would allow an escalation of therapy for unfavorable intermediate risk and de-escalation for favorable high-risk patients. We tested this hypothesis in a prospective trial of neoadjuvant/concurrent/adjuvant abiraterone acetate, prednisone, and LHRH agonist given for 6 months in conjunction with definitive prostate external beam RT. We now report the mature results of this trial. Materials/methods 37 men were enrolled in an IRB-approved NCT-registered prospective multi-center single arm investigator-initiated trial between January 2014 and August 2016. Eligibility required unfavorable intermediate risk of low volume high risk (NCCN) prostate cancer. All men were treated with 6 months of abiraterone acetate (1000mg daily), prednisone (5mg daily), and depot LHRH agonist initiated 8 weeks prior to standard fractionation RT to prostate/seminal vesicles +/- pelvis. Endpoints included PSA and testosterone (T) kinetics, biochemical progression-free survival (PFS), metastasis-free survival (MFS), overall survival (OS), and patient-reported quality-of-life. Results Enrolled patients were low volume (T1-2 disease and PSAs Conclusion For select men with aggressive prostate cancer, short course CAB with abiraterone acetate plus prednisone in combination with definitive prostate RT allows rapid T recovery and can provide excellent biochemical control up to 5 years. Short-course CAB is feasible for favorable high risk prostate cancer and may support optimization of patient quality of life. Prospective randomized trials should be considered.

Introduction Although there are over 500 mobile health (mHealth) applications (apps) available for download in the field of oncology, little research has addressed their acceptability among health care providers. In addition, the providers’ perspectives regarding patient app use has been largely unexamined. We conducted a qualitative study to explore opportunities and barriers for mHealth app use for oncology care. Methods We developed a structured interview guide focusing on acceptability, appropriateness, feasibility, and sustainability of the use of apps in cancer care. We interviewed 15 oncology providers about their attitudes and preferences. De-identified audio recordings were transcribed and coded for emerging themes. Results Providers interviewed included physicians (n = 8) and advanced practice (n = 3) and supportive services (n = 4) providers who care for a wide range of cancer types; ages ranged from 32 to 68 years. Interviews lasted approximately 30 minutes. Oncology providers reported limited exposure to mHealth apps in patient care, but were generally open to recommending or prescribing apps in the future. Key themes included opportunities for mobile app use (including general health promotion, tracking symptoms, and engaging patients) and barriers to implementation (including access to technology, responsibility, workflow, and the source of the app itself). Conclusion Our results show openness among oncology providers to using mHealth technology as part of patient care, but concerns regarding implementation. Designing acceptable apps may be challenging and require involvement of key stakeholders, partnering with trustworthy institutions, and outcome-based research.

Over half of men who receive treatment for prostate suffer from a range of sexual problems that affect negatively their sexual health, sexual intimacy with their partners and their quality of life. In clinical practice, however, care for the sexual side effects of treatment is often suboptimal or unavailable. The goal of the current study is to test a web-based intervention to support the recovery of sexual intimacy of prostate cancer survivors and their partners after treatment. The study team developed an interactive, web-based intervention, tailored to type of treatment received, relationship status (partnered/non-partnered) and sexual orientation. It consists of 10 modules, six follow the trajectory of the illness and four are theme based. They address sexual side effects, rehabilitation, psychological impacts and coaching for self-efficacy. Each includes a video to engage participants, psychoeducation and activities completed by participants on the web. Tailored strategies for identified concerns are sent by email after each module. Six of these modules will be tested in a randomized controlled trial and compared to usual care. Men with localized prostate cancer with partners will be recruited from five academic medical centers. These couples (N = 140) will be assessed prior to treatment, then 3 months and 6 months after treatment. The primary outcome will be the survivors’ and partners’ Global Satisfaction with Sex Life, assessed by a Patient Reported Outcome Measure Information Systems (PROMIS) measure. Secondary outcomes will include interest in sex, sexual activity, use of sexual aids, dyadic coping, knowledge about sexual recovery, grief about the loss of sexual function, and quality of life. The impact of the intervention on the couple will be assessed using the Actor-Partner Interaction Model, a mixed-effects linear regression model able to estimate both the association of partner characteristics with partner and patient outcomes and the association of patient characteristics with both outcomes. The web-based tool represents a novel approach to addressing the sexual health needs of prostate cancer survivors and their partners that—if found efficacious—will improve access to much needed specialty care in prostate cancer survivorship. Clinicaltrials.gov registration # NCT02702453 , registered on March 3, 2016.

Long-term care for head and neck cancer (HNC) survivors is complex and requires coordination among multiple providers. Clinical practice guidelines highlight the role of primary care providers (PCPs) in screening for secondary cancer/recurrence, assessment of late/long-term side effects, and referrals for appropriate specialty management of toxicity. However, these responsibilities may be difficult to meet within the scope of primary care practice. We conducted this study to explore preferences, comfort, and knowledge of PCPs in the care of HNC survivors. We piloted a 40-item web-based survey developed with oncologist and PCP input targeted for family medicine and internal medicine providers. Responses were collected within a single university health system over 2 months. PCPs (n = 28; RR = 11.3%) were interested in learning about health promotion after cancer treatment (89%) and generally agree that their current practice patterns address healthy lifestyle behaviors (82%). However, only 32% of PCPs felt confident they could manage late/long-term side effects of chemotherapy, radiation, or surgery. Only 29% felt confident they could provide appropriate cancer screening. Looking at shared care responsibilities with oncology providers, PCPs perceived being responsible for 30% of care in the first year after treatment and 81% of care after 5 years. Seventy-one percent of PCPs agreed that oncologists provided them necessary information, yet 32% of PCPs found it difficult to coordinate with cancer providers. While these PCPs perceive increased care responsibility for long-term survivors, most are uncomfortable screening for recurrence and managing late/long-term side effects. Education and mutual coordination between PCPs and oncology providers may improve survivor care.

Purpose Radiation oncologists are frequently involved in providing palliative and supportive care (PSC) for patients with advanced cancers through delivery of palliative radiation. Whether they are confident in their ability to assess and initiate treatments for pain, nonpain, and psychosocial distress is unknown. The American Society for Radiation Oncology surveyed its practicing members in the United States on self-assessment of their primary PSC skills and access to continuing medical education on PSC. Methods We electronically surveyed 4093 practicing radiation oncologists in the United States. The survey consisted of 16-questions in 5 sections 1 : demographics, 2 PSC training, 3 domains of PSC, 4 perceived barriers as a radiation oncologist to initiate advanced care planning, and 5 discussion of prognosis. Results The survey was e-mailed to 4093 American Society for Radiation Oncology members, and 649 responses were received (response rate 16%). The majority (91%) of radiation oncologists surveyed believe PSC is an important competency for radiation oncologists. Most radiation oncologists reported that they are moderately confident in their ability to assess and manage pain and gastrointestinal symptoms, but less confident in their ability to manage anorexia, anxiety, and depression. Despite areas of decreased confidence, a large number (42%) of radiation oncologists do not receive any additional PSC education beyond their residency training. Lastly, a perceived fear of upsetting referring medical oncologists and lack of clinic time are concerns for radiation oncologists who may want to initiate goals of care/advance care planning discussions with patients and their families. Conclusion Radiation oncologists are more confident in their ability to assess and manage pain than in their ability to manage depression, anxiety, anorexia, and fatigue. There is a need for increasing continuing medical educational efforts in PSC for practicing radiation oncologists, and strengthening PSC training in residency programs.

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

INTRODUCTION AND OBJECTIVES:Women with cervical and endometrial cancers treated with radiation therapy (RT) can experience injury to surrounding normal tissues leading to genitourinary dysfunction....

Purpose The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer. Methods and Materials The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength. Results Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques. Conclusions Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base—especially for ultrahypofractionation—highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

TPS5098 Background: Radiation therapy (RT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases not identified with conventional imaging (CIM). Given PET's greater sensitivity and specificity, its findings are increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of the otherwise non-tailored SOC approach. Improved systemic control and disease detection with molecular imaging have led to increasing use of focally ablative metastasis-directed RT, to delay or enhance systemic therapy through increased local control. There is also interest in earlier use of systemic therapy; apalutamide (Apa) is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castration-resistant and metastatic castration-sensitive PC. This study will evaluate whether pts with PET-detected lesions benefit from such local or systemic treatment intensification approaches. Methods: PC pts with post-RP BCR (PSA>0.5ng/mL; >0.2ng/mL if within 12 mos of RP) and no metastases on CIM who are candidates for SOC ST (RT to prostate bed and pelvic nodes with STAD) are eligible. Prior to study registration, pts undergo SOC baseline PET (18F-fluciclovine but PSMA radiotracers permitted pending commercial availability). Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic metastases). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- metastasis-directed RT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of metastasis-directed RT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified log-rank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in the experimental arm from 61.5% in the control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. Clinical trial information: NCT04423211.

This exploratory analysis of a randomized clinical trial evaluates the association of bone metastasis count and location with survival benefit from prostate radiotherapy in patients with newly diagnosed metastatic prostate cancer., Key Points Question Are bone metastatic burden and site associated with survival benefit from the addition of prostate radiotherapy (RT) to standard-of-care systemic therapy in newly diagnosed metastatic prostate cancer? Findings This exploratory analysis of 1939 participants in a randomized clinical trial shows that survival benefit following prostate RT gradually diminished with increasing bone metastasis number, with survival benefit most pronounced in patients with up to 3 bone metastases. Prostate RT was associated with greater overall and failure-free survival in patients with only nonregional lymph node metastasis (M1a) or 3 or fewer bone metastases without visceral metastasis. Meaning In patients with prostate cancer, bone metastatic burden and metastasis location may be useful in predicting survival benefit from prostate RT., Importance Prostate radiotherapy (RT) improves survival in men with low-burden metastatic prostate cancer. However, owing to the dichotomized nature of metastatic burden criteria, it is not clear how this benefit varies with bone metastasis counts and metastatic site. Objective To evaluate the association of bone metastasis count and location with survival benefit from prostate RT. Design, Setting, and Participants This exploratory analysis of treatment outcomes based on metastatic site and extent as determined by conventional imaging (computed tomography/magnetic resonance imaging and bone scan) evaluated patients with newly diagnosed metastatic prostate cancer randomized within the STAMPEDE trial’s metastasis M1 RT comparison. The association of baseline bone metastasis counts with overall survival (OS) and failure-free survival (FFS) was assessed using a multivariable fractional polynomial interaction procedure. Further analysis was conducted in subgroups. Interventions Patients were randomized to receive either standard of care (androgen deprivation therapy with or without docetaxel) or standard of care and prostate RT. Main Outcomes and Measures The primary outcomes were OS and FFS. Results A total of 1939 of 2061 men were included (median [interquartile range] age, 68 [63-73] years); 1732 (89%) had bone metastases. Bone metastasis counts were associated with OS and FFS benefit from prostate RT. Survival benefit decreased continuously as the number of bone metastases increased, with benefit most pronounced up to 3 bone metastases. A plot of estimated treatment effect indicated that the upper 95% CI crossed the line of equivalence (hazard ratio [HR], 1) above 3 bone metastases without a detectable change point. Further analysis based on subgroups showed that the magnitude of benefit from the addition of prostate RT was greater in patients with low metastatic burden with only nonregional lymph nodes (M1a) or 3 or fewer bone metastases without visceral metastasis (HR for OS, 0.62; 95% CI, 0.46-0.83; HR for FFS, 0.57; 95% CI, 0.47-0.70) than among patients with 4 or more bone metastases or any visceral/other metastasis (HR for OS, 1.08; 95% CI, 0.91-1.28; interaction P = .003; HR for FFS, 0.87; 95% CI, 0.76-0.99; interaction P = .002). Conclusions and Relevance In this exploratory analysis of a randomized clinical trial, bone metastasis count and metastasis location based on conventional imaging were associated with OS and FFS benefit from prostate RT in M1 disease. Trial Registration ClinicalTrials.gov Identifier: NCT00268476; ISRCTN.com Identifier: ISRCTN78818544

90 Background: ADT with salvage RT improves survival for men with PSA recurrence after RP. Current standard duration of ADT for high risk PSA recurrence is up to 2 years with RT; therefore shortening but intensifying systemic therapy may improve outcomes. The STREAM trial showed 6 mo of enzalutamide added to ADT/RT had a 3-year progression free survival (PFS) of 53% in high risk patients including lymph node (LN) positive. Given that docetaxel improves survival in men with mHSPC, we evaluated the combination of salvage RT, ADT/apalutamide and docetaxel in this setting. Methods: STARTAR is a multicenter phase 2 trial for salvage treatment of PSA recurrent PC following RP conducted within the US Dept. of Defense Prostate Cancer Clinical Trials Consortium (DOD PCCTC). Key inclusion criteria included PC with Gleason 7 with T3/positive margin/1-4 positive LNs or Gleason 8-10 disease and PSA relapse within 4 years of RP (min PSA 0.2 ng/mL to max PSA 4 ng/mL). Men with up to 4 positive resected LNs were eligible. Men started ADT with apalutamide, continued with RT (66-74 Gy to the prostate bed +/- pelvic LNs over 6-8 weeks), and finally completed docetaxel 75mg/m2 IV q3 weeks for 6 cycles. Men were treated with ADT and apalutamide for approximately 9 months. The primary endpoint was PSA PFS at 36 months. This interim analysis evaluated secondary endpoints of 1-year PSA recurrence, testosterone recovery, and safety of this treatment sequence. Results: From 3/2018 to 12/2019, 39 men were enrolled at Duke, Wake Forest, Cornell, and the GU Research Network. With a data cutoff in 9/2020, median follow up from enrollment was 14 months. Baseline patient characteristics included Gleason 4+3 = 7 in 54% and Gleason 8-10 in 46%, and 23% LN positive; median PSA at the time of enrollment was 0.58 ng/mL (range 0.21-3.40) and the median time from RP to enrollment was 7 mo (range 2-98). At 1 year, there have been no progression events with 38% (12/31) of men with post-treatment testosterone recovery into normal range (recovery time median 10 mos [1-17 mos]). Common adverse events (AEs) of any-grade at least possibly related to the regimen were 98% hot flashes, 88% fatigue, 77% alopecia, 57% dysgeusia, and 53% rash (28% grade 1; 15% grade 2, 10% grade 3), with neutropenia as the most common grade 3/4 AE (27/39 men, 70%) with two grade 3 febrile neutropenia. Conclusions: In this first phase 2 trial of ADT, apalutamide, radiation, and 6 cycles docetaxel in the salvage setting for high risk PSA recurrence, short term outcomes are excellent with no recurrences at 12 months of follow-up. This salvage treatment was well tolerated in the majority of men with the exception of a high rate of drug rashes and neutropenia related to the course of treatment, in line with known safety profiles of the study agents. Clinical trial information: NCT03311555.

TPS267 Background: Radiation therapy (RT) to the prostate bed and pelvic nodes with short-term androgen deprivation therapy (STAD) is considered a standard of care (SOC) salvage therapy (ST) paradigm for prostate cancer (PC) patients (pts) with post-prostatectomy (RP) biochemical recurrence (BCR). Fluciclovine-PET/CT imaging is FDA-approved in this setting, with improved accuracy for detection of metastases (mets) not identified with conventional imaging (CIM). Given greater sensitivity and specificity of PET, its findings are being increasingly but variably applied to justify modification or omission of SOC therapies without high-level evidence of clinical benefit. PET may help identify candidates for local or systemic treatment intensification of otherwise non-tailored SOC. Earlier detection of mets with molecular imaging has led to increasing use of focally ablative met-directed RT, to delay or enhance systemic therapy through better local control. There is also interest in earlier use of advanced systemic therapy; apalutamide (Apa) is a nonsteroidal antiandrogen with established efficacy in improving overall and radiographic progression-free survival (PFS) for non-metastatic castrate-resistant and metastatic castration-sensitive PC, and potential activity for low-volume mets. This study will evaluate whether pts with PET-detected lesions benefit from such local or systemic treatment intensification approaches. Methods: PC pts with post-RP BCR (PSA>0.5ng/mL; >0.2 if RP within 12 mos), and negative CIM who are candidates for SOC ST (RT to prostate bed and pelvic nodes + STAD) and undergo SOC baseline PET are eligible. The study will initially use 18F-fluciclovine but permit additional radiotracers based on FDA approval and availability. Based on institutional clinical interpretation of the SOC PET, pts will be placed in Cohort 1 (PET-negative) or 2 (PET-positive for extra-pelvic mets). Cohort 1 will be randomized to SOC ST +/- Apa for 6 months and Cohort 2 will be randomized to SOC ST and Apa +/- met-directed RT to PET-positive lesions. The primary endpoint is PFS, defined as time from randomization to radiographic progression on CIM, symptomatic disease or death. Primary objectives are to evaluate whether addition of Apa to SOC ST and addition of met-directed RT to SOC ST and Apa could prolong PFS in Cohorts 1 and 2, respectively. For Cohort 1, 480 pts will be randomized with 85% power to distinguish 5-year PFS rate of 90% (Apa arm) vs. 80% (SOC arm) using one-sided stratified logrank test with type I error of 0.025. For Cohort 2, 324 pts will be randomized with 85% power to distinguish 5-year PFS rate of 76.5% in experimental arm from 61.5% in control arm. Secondary endpoints include overall and event-free survival, toxicity, and PET progression. Trial was activated on October 8, 2020; NCT04423211. Acknowledgement: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180794, U10CA180820, U10CA180868, U10CA180888, U10CA180821, UG1CA233196, UG1CA233253, UG1CA233277, UG1CA233328, and UG1CA233330. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government. Clinical trial information: NCT 04423211.

During the past 10 years, interventions supporting couples’ sexual recovery after prostate cancer treatment have been developed and tested. We sought to review these intervention studies to determine the degree to which they have been effective. Eleven studies (4 pilot studies and 7 randomized controlled trials) were reviewed. Our findings suggest that outcomes, such as sexual function, relationship satisfaction, or intimacy, are minimally improved. However, the interventions succeed in increasing couples’ knowledge of the treatment-related sexual side effects and rehabilitation, men’s use of ED treatments, partners’ attitudes to ED, and couples’ maintenance of sexual engagement. Based on the findings, we propose that further research on couple-based interventions continue to identify meaningful outcomes sensitive to change with the goal of protecting couples from losing sexual relationships despite treatment-related functional losses. An analytic approach that measures patient-partner mutual influence on outcomes is also recommended.

Purpose To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

Purpose We aimed to update a previously published, multi-institutional nomogram of outcomes for salvage radiotherapy (SRT) following radical prostatectomy (RP) for prostate cancer, including patients treated in the contemporary era. Methods Individual data from node-negative patients with a detectable post-RP prostate-specific antigen (PSA) treated with SRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 10 academic institutions. Freedom from biochemical failure (FFBF) and distant metastases (DM) rates were estimated, and predictive nomograms were generated. Results Overall, 2,460 patients with a median follow-up of 5 years were included; 599 patients (24%) had a Gleason score (GS) ≤ 6, 1,387 (56%) had a GS of 7, 244 (10%) had a GS of 8, and 230 (9%) had a GS of 9 to 10. There were 1,370 patients (56%) with extraprostatic extension (EPE), 452 (18%) with seminal vesicle invasion (SVI), 1,434 (58%) with positive surgical margins, and 390 (16%) who received ADT (median, 6 months). The median pre-SRT PSA was 0.5 ng/mL (interquartile range, 0.3 to 1.1). The 5-yr FFBF rate was 56% overall, 71% for those with a pre-SRT PSA level of 0.01 to 0.2 ng/mL (n = 441), 63% for those with a PSA of 0.21 to 0.50 ng/mL (n = 822), 54% for those with a PSA of 0.51 to 1.0 ng/mL (n = 533), 43% for those with a PSA of 1.01 to 2.0 ng/mL (n = 341), and 37% for those with a PSA > 2.0 ng/mL (n = 323); P < .001. On multivariable analysis, pre-SRT PSA, GS, EPE, SVI, surgical margins, ADT use, and SRT dose were associated with FFBF. Pre-SRT PSA, GS, SVI, surgical margins, and ADT use were associated with DM, whereas EPE and SRT dose were not. The nomogram concordance indices were 0.68 (FFBF) and 0.74 (DM). Conclusion Early SRT at low PSA levels after RP is associated with improved FFBF and DM rates. Contemporary nomograms can estimate individual patient outcomes after SRT in the modern era.

Objectives The management of patients with postprostatectomy salvage radiotherapy (SRT) presents radiation oncologists (ROs) with multiple treatment decisions that may impact outcomes. As the evidence addressing these issues is limited to retrospective data, it was hypothesized that widely disparate treatment paradigms exist. Methods A 21-question survey was sent through SurveyMonkey to members of the American Society of Radiation Oncology. Results A total of 999 ROs responded. Threshold rPSA values to initiate SRT ranged from 0.1 to 1 ng/mL. The highest dose prescribed by ROs ranged from 70.2 Gy. Elective lymph node irradiation was offered by 74%, and the majority (64%) referenced the Roach formula, Kattan nomogram, or D'Amico risk stratification to decide when it was appropriate. There was variability in pelvic field design with a preference to place the superior field border at either the upper, middle, or lower sacroiliac joint by 57.6%, 28.8%, and 13.6% of respondents, respectively. Adjuvant androgen deprivation therapy (ADT) was offered by 74%. Conclusions Disparate treatment paradigms exist for SRT that may impact patient outcomes. Variability includes patient selection, treatment design, and recommendations for ADT. Many reference formulas to predict the benefit of pelvic lymph node irradiation that are not yet validated in the postprostatectomy setting. These data make it clear that well-designed, prospective clinical trials are needed to better evaluate the role of larger treatment fields, dose escalation, and ADT for the thousands of patients who are treated with postprostatectomy SRT each year.

211 Background: Low-volume de novo metastatic hormone-sensitive prostate cancer (mHSPC) has historically been treated with lifelong androgen deprivation therapy (ADT). Recently, however, the addition of several advanced therapeutic options – radiation therapy (RT) to the primary, advanced hormonal therapy agents such as abiraterone acetate/prednisone (AAP), and chemotherapy – to ADT have been shown to improve survival in low-volume mHSPC. The objective of this study was to compare the cost-effectiveness of treating low-volume mHSPC patients upfront with RT+ADT, AAP+ADT, or docetaxel+ADT. Methods: A Markov-based cost-effectiveness analysis was constructed comparing three treatment strategies for low-volume mHSPC patients: (1) upfront RT+ADT --> salvage AAP+ADT --> salvage docetaxel+ADT; (2) upfront AAP+ADT --> salvage docetaxel+ADT, and (3) upfront docetaxel+ADT --> salvage AAP+ADT. Transition probabilities were calculated using data from STAMPEDE arms C/G/H, COU-AA-301, COU-AA-302, and TAX-327. RT was delivered via five-fraction stereotactic body radiation therapy. The analysis utilized a 10-year time horizon, and a $100,000/quality adjusted life year (QALY) willingness-to-pay threshold. Utilities were extracted from the literature; costs were taken from Medicare fee schedules and VA oral drug contracts. Results: At 10 years, total cost was $140K, $259K, and $189K, with total QALYs of 4.66, 5.03, and 3.72 for strategies (1) upfront RT+ADT, (2) upfront AAP+ADT, and (3) upfront docetaxel+ADT, respectively. Compared to upfront RT+ADT, upfront AAP+ADT was not cost-effective (ICER: $321K/QALY). This result remained unchanged even after modification of various model inputs in 1-way sensitivity analysis. Upfront docetaxel+ADT was both more costly and less effective than upfront RT+ADT (ICER: -$53K/QALY). Conclusions: At 10 years, RT+ADT is cost-effective compared to other advanced systemic therapy options alone, and should be considered as a viable treatment strategy in all patients with a low-burden of metastatic disease. Additional studies are needed to determine whether any benefit exists in combining RT to the primary with upfront advanced systemic therapy.