Value of routine follow-up for recurrence detection after treatment with curative intent for laryngeal squamous cell carcinoma.

INTRODUCTION: The benefits of routine follow-up after treatment of primary laryngeal squamous cell carcinoma (LSCC) remain disputed. Guidelines worldwide are consensus-based, and evidence for specific subgroups is lacking. This study evaluates routine LSCC follow-up including flexible endoscopy for detecting locoregional recurrence (LRR). METHODS: A retrospective cohort of 413 LSCC patients treated between 2006 and 2012 was analysed. The cumulative risk of LRR was calculated. Routine follow-up was evaluated by follow-up visit (routine or interval) at which LRR was detected, LRR treatment intent, and overall survival (OS). Analyses were stratified by early (I-II) and advanced (III-IV) TNM-stage. RESULTS: There were 263 (64 %) patients with early-stage and 132 (32 %) patients with advanced-stage LSCC. One-, two- and five-year cumulative risks for LRR after early-stage LSCC were 8 %, 18 %, and 26 %. For advanced-stage LSCC, cumulative risks of LRR were 20 %, 30 %, and 35 %. Of all 69 LRRs after early-stage LSCC, 72 % were routine-detected, 81 % were symptomatic, and 90 % received curative-intent treatment. Of all 45 LRRs following advanced-stage LSCC, 42 % were routine-detected, 84 % were symptomatic, and 62 % received curative-intent treatment. Five-year OS of early-stage LSCC with routine-detected LRR was 70 %, and 72 % for interval-detection (log-rank-p = 0.91). Five-year OS of advanced-stage LSCC with routine-detected LRR was 37 %, and 18 % for interval-detection (log-rank-p = 0.06). CONCLUSIONS: Routine follow-up for detecting asymptomatic recurrences seems redundant for early-stage LSCC. After advanced-stage LSCC, no asymptomatic recurrences were detected beyond one year posttreatment despite regular follow-up. Emphasis should be on other follow-up aspects, such as psychosocial support, especially after one year posttreatment.

Evaluation of a remote monitoring app in head and neck cancer follow-up care.

BACKGROUND: A remote monitoring app was developed for head and neck cancer (HNC) follow-up during the SARS-CoV-2 pandemic. This mixed-methods study provides insight in the usability and patients' experiences with the app to develop recommendations for future use. METHODS: Patients were invited to participate if they were treated for HNC, used the app at least once and were in clinical follow-up. A subset was selected for semi-structured interviews through purposive sampling considering gender and age. This study was conducted between September 2021-May 2022 at a Dutch university medical center. RESULTS: 135 of the 216 invited patients completed the questionnaire, resulting in a total mHealth usability score of 4.72 (± 1.13) out of 7. Thirteen semi-structured interviews revealed 12 barriers and 11 facilitators. Most of them occurred at the level of the app itself. For example, patients received no feedback when all their answers were normal. The app made patients feel more responsible over their follow-up, but could not fulfill the need for personal contact with the attending physician. Patients felt that the app could replace some of the outpatient follow-up visits. CONCLUSIONS: Our app is user-friendly, makes patients feel more in control and remote monitoring can reduce the frequency of outpatient follow-up visits. The barriers that emerged must be resolved before the app can be used in regular HNC follow-up. Future studies should investigate the appropriate ratio of remote monitoring to outpatient follow-up visits and the cost-effectiveness of remote monitoring in oncology care on a larger scale.

Individualised follow-up for head and neck cancer-design of a prospective cohort study to assess its feasibility.

INTRODUCTION: It is a common practice for many cancer types to monitor patients after treatment to detect new disease manifestations early. For head and neck cancer (HNC), however, long-term routine follow-up is up for debate for several reasons. The benefits of prolonged routine follow-up on survival have not been proven. Also, cancer follow-up is putting increasing pressure on healthcare resources due to rising incidence and survival rates. Therefore, this study investigates a novel follow-up approach among HNC patients, giving them the opportunity to choose their own follow-up programme. METHODS AND ANALYSIS: HNC patients are offered a decision-aided choice between standardised or individualised follow-up after 1.5 years of uncomplicated guideline-prescribed follow-up. Standardised follow-up entails continuing the 5-year guideline-prescribed schedule. Individualised follow-up means the patient only attends the outpatient clinic on their own initiative in case of physical symptoms or supportive care needs. Patients are educated on self-examination and when a control visit is necessary. The primary outcome measure is the feasibility of offering patients this choice. Secondary outcome measures are quality of life, costs, productivity loss and detection of new disease. ETHICS AND DISSEMINATION: We believe that it is essential to let patients determine their follow-up programme based on their own values and preferences. If this choice is feasible, it can be implemented and investigated in other HNC care centres. TRIAL REGISTRATION NUMBER: NCT05386225.

Coronary artery calcifications on breast cancer radiotherapy planning CT scans and cardiovascular risk: What do patients want to know?

BACKGROUND: Coronary artery calcifications (CAC) is a strong predictor of cardiovascular disease (CVD), which can be automatically quantified on routine breast radiotherapy planning computed tomography (CT) scans. Around 8% of patients have (very) high CAC scores and corresponding increased risks of CVD. AIM: This study explores whether, how, and under what conditions women with breast cancer want to be informed about their CAC-based CVD risk. METHODS: A cross-sectional survey study was conducted in a random sample of UMBRELLA, a prospective breast cancer cohort. Participants (n = 79) filled out a questionnaire about their knowledge on the CVD risk following breast cancer, their interest in being informed about their CVD risk based on CAC score, and preferences on how they would want to receive this information. RESULTS: Most participants (66%) were not aware that the presence of CAC indicates an increased CVD risk. Participants indicated that they were not or only slightly aware of the risk of treatment-induced cardiotoxicity (48%), and that the risk of cardiotoxicity was higher in patients with pre-existing CVD risk factors (82%). The vast majority (90%) indicated that they want to be informed about in increased CAC-based CVD risk. CONCLUSIONS: The majority of patients with breast cancer wants to be informed about their CAC-based CVD risk. With the majority of patients with breast cancer undergoing radiotherapy, and with low cost and automated options for accurate CAC measurement in planning CT scans, it is important to develop strategies to manage patients with an increased CAC-based risk of CVD.

Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer.

IMPORTANCE: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. OBJECTIVE: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter cohort study of 15 915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. EXPOSURES: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). MAIN OUTCOMES AND MEASURES: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. RESULTS: Of the 15 915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15 879 (99.8%) were women. Seventy percent (n = 11 179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). CONCLUSIONS AND RELEVANCE: This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03206333.

Introducing Decision Aids into Routine Prostate Cancer Care in The Netherlands: Implementation and Patient Evaluations from the Multi-regional JIPPA Initiative.

Uptake of decision aids (DAs) in daily routine is low, resulting in limited knowledge about successful DA implementation at a large scale. We assessed implementation rates after multi-regional implementation of three different prostate cancer (PCa) treatment DAs and patient-perceived barriers and facilitators to use a DA. Thirty-three hospitals implemented one out of the three DAs in routine care. Implementation rates for each DA were calculated per hospital. After deciding about PCa treatment, patients (n = 1033) completed a survey on pre-formulated barriers and facilitators to use a DA. Overall DA implementation was 40%. For each DA alike, implementation within hospitals varied from incidental (< 10% of eligible patients receiving a DA) to high rates of implementation (> 80%). All three DAs were evaluated positively by patients, although concise and paper DAs yielded higher satisfaction scores compared with an elaborate online DA. Patients were most satisfied when they received the DA within a week after diagnosis. Pre-formulated barriers to DA usage were experienced by less than 10% of the patients, and most patients confirmed the facilitators. Many patients received a DA during treatment counseling, although a wide variation in uptake across hospitals was observed for each DA. Most patients were satisfied with the DA they received. Sustained implementation of DAs in clinical routine requires further encouragement and attention.

Implementation of a decision aid for localized prostate cancer in routine care: A successful implementation strategy.

For the treatment choice of localized prostate cancer, effective patient decision aids have been developed. The implementation of decision aids in routine care, however, lags behind. Main known barriers are lack of confidence in the tool, lack of training on its use, lack of resources and lack of time. A new implementation strategy addresses these barriers. Using this implementation strategy, the implementation rate of a decision aid was measured in eight hospitals and questionnaires were filled out by 24 care providers and 255 patients. The average implementation rate was 60 per cent (range 31%-100%). Hardly any barriers remained for care providers. Patients who did not use the decision aid appeared to be more unwilling than unable to use the decision aid. By addressing known barriers, that is, informing care providers on the effectiveness of the decision aid, providing instructions on its use, embedding it in the existing workflow and making it available free of charge, a successful implementation of a prostate cancer decision aid was reached.

Uptake and usage of an online prostate cancer treatment decision aid in Dutch clinical practice: A quantitative analysis from the Prostate Cancer Patient Centered Care trial.

Implementation of patient's decision aids in routine clinical care is generally low. This study evaluated uptake and usage of a novel Dutch web-based prostate cancer treatment decision aid within the Prostate Cancer Patient Centered Care trial. From an estimated total patient sample of 1006 patients, 351 received a decision aid (35% implementation rate; hospital ranges 16%-84%). After receipt of the decision aid, most patients accessed the decision aid, utilized most functions, although not completely, and discussed the decision aid summary in a subsequent consultation with their care provider. Including nurses for dissemination of decision aids seemed to positively affect decision aid uptake. Once received, patients seemed able to use the decision aid and engage in shared decision-making as intended; however, decision aid uptake and complete usage of all decision aid components should be further improved. Prior to the diagnosis consultation, handing out of the decision aid should be prepared.

Does a decision aid for prostate cancer affect different aspects of decisional regret, assessed with new regret scales? A randomized, controlled trial.

OBJECTIVE: To develop and validate new regret scales and examine whether a decision aid affects different aspects of regret in the treatment choice for prostate cancer. METHODS: This was a multicentre trial (three sites) with imbalanced randomization (1 : 2). From 2008 to 2011, patients with localized prostate cancer were randomized 1 : 2 to usual care (N = 77) or usual care plus a decision aid presenting risks and benefits of different treatments (N = 163). The treatments were surgery and (external or interstitial) radiotherapy. Regret was assessed before, and 6 and 12 months after treatment, using the Decisional regret scale by Brehaut et al. (Medical Decision Making, 23, 2003, 281), and three new scales focusing on process, option and outcome regret. The relation between decision aid and regret was analysed by anova. RESULTS: The concurrent validity of the new regret scales was confirmed by correlations between regret and anxiety, depression, decision evaluation scales and health-related quality of life. With a decision aid, patient participation was increased (P = 0.002), but regret was not. If anything, in patients with serious morbidity the decision aid resulted in a trend to less option regret and less Brehaut regret (P = 0.075 and P = 0.061, with effect sizes of 0.35 and 0.38, respectively). Exploratory analyses suggest that high-risk patients benefitted most from the decision aid. CONCLUSION: The new regret scales may be of value in distinguishing separate aspects of regret. In general, regret was not affected by the decision aid. In patients with serious morbidity, a trend to lower option regret with a decision aid was observed.

Choice between prostatectomy and radiotherapy when men are eligible for both: a randomized controlled trial of usual care vs decision aid.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Many patients are eligible for more than one treatment option for prostate cancer. In usual care, urologists have a large influence on the treatment choice. Decision aids, providing balanced information on the pros and cons of different treatment options, improve the match between patient preferences and treatment received. In men eligible for both surgery and external beam radiotherapy, treatment choice differed by hospital. Across the participating hospitals, the decision aid consistently led to fewer patients remaining undecided on their treatment preference and more patients choosing brachytherapy. OBJECTIVES: To examine the treatment choice for localized prostate cancer in selected men who were eligible for both prostatectomy and radiotherapy. To examine whether increased patient participation, using a decision aid, affected the treatment choice. PATIENTS AND METHODS: From 2008 to 2011, 240 patients with localized prostate cancer were enrolled from three separate hospitals. They were selected to be eligible for both prostatectomy and external beam radiotherapy. Brachytherapy was a third option for about half of the patients. In this randomized controlled trial, patients were randomized to a group which only discussed their treatment with their specialist (usual care group) and a group which received additional information from a decision aid presented by a researcher (decision aid group). The decision aid was based on a literature review. Predictors of treatment choice were examined. RESULTS: Treatment choice was affected by the decision aid (P = 0.03) and by the hospital of intake (P < 0.001). The decision aid led to more patients choosing brachytherapy (P = 0.02) and fewer patients remaining undecided (P < 0.05). Prostatectomy remained the most frequently preferred treatment. Age, tumour characteristics or pretreatment urinary, bowel or erectile functioning did not affect the choice in this selected group. Patients choosing brachytherapy assigned more weight to convenience of the procedure and to maintaining erectile function. CONCLUSIONS: Traditionally, patient characteristics differ between surgery and radiotherapy groups, but not in this selected group of patients. Men eligible for both prostatectomy and radiotherapy mostly preferred prostatectomy, and the treatment choice was influenced by the hospital they visited. Giving patients evidence-based information, by means of a decision aid, led to an increase in brachytherapy.

Depression related to (neo)adjuvant hormonal therapy for prostate cancer.

BACKGROUND: We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy. METHODS: Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide+Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis. RESULTS: During the course of hormonal therapy, depression was significantly heightened by both hormone use (p<0.001) and poor prognosis (p<0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p<0.01). The increase was, however, small. CONCLUSIONS: Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

Efficacy and tolerance of salvage radiotherapy after radical prostatectomy, with emphasis on high-risk patients suited for adjuvant radiotherapy.

BACKGROUND AND PURPOSE: Goals of this study are to report the outcomes and tolerance of salvage radiotherapy (SRT) after prostatectomy, to identify risk factors for failure after SRT and to evaluate how these results compare with published results of immediate post-operative adjuvant radiotherapy (ART). MATERIAL AND METHODS: Men receiving SRT for elevated PSA levels after radical prostatectomy (RP) were included. Biochemical progression-free survival (bPFS), overall survival (OS) and disease-specific survival (DSS) were estimated. Risk factors for biochemical failure and death were evaluated. Late toxicity and quality of life were evaluated. Secondary bPFS (defined as bPFS from prostatectomy until progression after radiotherapy) was calculated for high-risk patients (pT3 and/or positive surgical margins) in order to compare SRT outcomes with ART. RESULTS: 197 Men were included. Five-year bPFS after SRT was 59% (95% CI 49-69%). Five-year OS and DSS were 90% (85-96%) and 97% (93-100%), respectively. Capsular perforation (pT≥T3), negative surgical margins and serum PSA>1 ng/ml at the start of RT were significant predictors of lower bPFS. Patients without any negative factors had a 5-year bPFS of 89%. No severe late toxicity was reported. Five-year secondary bPFS for SRT in high-risk patients was 78% and comparable with published results for ART. CONCLUSIONS: Salvage radiotherapy for patients with organ-confined prostate cancer was effective and well tolerated. SRT outcomes were comparable with published ART results for high-risk patients. Initially monitoring serum PSA and considering early SRT for these patients are not harmful and might be a valuable alternative for immediate ART.

Offering a treatment choice in the irradiation of prostate cancer leads to better informed and more active patients, without harm to well-being.

PURPOSE: To examine, in prostate cancer patients, the effect of (1) being offered a choice between radiation doses in three-dimensional conformal radiotherapy, and of (2) accepting or declining the possibility to choose. METHODS AND MATERIALS: A total of 150 patients with localized prostate cancer (T1-3N0M0) were offered a choice with a decision aid between two radiation doses (70 and 74 Gy). A control group of 144 patients received a fixed radiation dose without being offered a choice. Data were collected at baseline (before choice), before treatment (after choice), and 2 weeks and 6 months after treatment completion. RESULTS: Compared with the control group, the involvement group, receiving the decision aid, showed increased participation in decision making (p < 0.001), increased knowledge (p < 0.001), and improved risk perception (p < 0.001); they were more satisfied with the quality of information (p = 0.002) and considered their treatment a more appropriate treatment (p = 0.01). No group differences were found in well-being (e.g., general health, European Organization for Research and Treatment of Cancer quality of life, anxiety). Within the involvement group, accepting or declining the option to choose did not affect well-being either. CONCLUSIONS: Offering a choice of radiation dose, with a decision aid, increased involvement in decision making and led to a better-informed patient. In contrast to earlier suggestions, a strong increase in involvement did not result in improved well-being; and in contrast to clinical concerns, well-being was not negatively affected either, not even in those patients who preferred to leave the decision to their physician. This study shows that older patients, such as prostate cancer patients, can be informed and involved in decision making.

Doctors' and patients' preferences for participation and treatment in curative prostate cancer radiotherapy.

PURPOSE: Physicians hold opinions about unvoiced patient preferences, so-called substitute preferences. We studied whether doctors can predict preferences of patients supported with a decision aid. METHODS: A total of 150 patients with prostate cancer facing radiotherapy were included. After the initial consultation, without discussing any treatment choice, physicians gave substitute judgments for patients' decision-making and radiation dose preferences. Physicians knew that several weeks later, patients would be empowered by a decision aid supporting a choice between two radiation doses involving a trade-off between disease-free survival and adverse effects. Subsequently, patient preferences for decision making (whether or not they wanted to choose a radiation dose) and for treatment (low or high dose) were obtained. The chosen radiation dose actually was administered. RESULTS: Of the patients studied, 79% chose a treatment; physicians believed that 66% of the patients wanted to choose. Agreement was poor (64%; = 0.13; P = .11), and was better as patients became more hopeful (odds ratio [OR] = 4.4 per unit; P = .001) and as physicians' experience increased (OR = 1.09 per year; P = .02). Twenty percent of physicians' preferences, 51% of physicians' substitute preferences, and 71% of patients' preferences favored the lower dose; agreement was again poor (70%; = 0.2; P = .03). CONCLUSION: Physicians had problems predicting the preferences of patients empowered with a decision aid. They slightly underestimated patients' decision-making preferences, and underestimated patients' preferences for the less toxic treatment. Counseling might be improved by first informing patients-possibly using a decision aid--before discussing patient preferences.

Do patients with localized prostate cancer treatment really want more aggressive treatment?

PURPOSE: Examine whether patients with prostate cancer choose the more aggressive of two radiotherapeutic options, whether this choice is reasoned, and what the determinants of the choice are. PATIENTS AND METHODS: One hundred fifty patients with primary prostate cancer (T(1-3)N(0)M(0)) were informed by means of a decision aid of two treatment options: radiotherapy with 70 Gy versus 74 Gy. The latter treatment is associated with more cure and more toxicity. The patients were asked whether they wanted to choose, and if so which treatment they preferred. They also assigned importance weights to the probability of various outcomes, such as survival, cure and adverse effects. Patients who wanted to choose their own treatment (n = 119) are described here. RESULTS: The majority of these patients (75%) chose the lower radiation dose. Their choice was highly consistent (P < or = .001), with the importance weights assigned to the probability of survival, cure (odds ratio [OR] = 6.7 and 6.9) and late GI and genitourinary adverse effects (OR = 0.1 and 0.2). The lower dose was chosen more often by the older patients, low-risk patients, patients without hormone treatment, and patients with a low anxiety or depression score. CONCLUSION: Most patients with localized prostate cancer prefer the lower radiation dose. Our findings indicate that many patients attach more weight to specific quality-of-life aspects (eg, GI toxicity) than to improving survival. Treatment preferences of patients with localized prostate cancer can and should be involved in radiotherapy decision making.

Do prostate cancer patients want to choose their own radiation treatment?

PURPOSE: The aims of this study were to investigate whether prostate cancer patients want to be involved in the choice of the radiation dose, and which patients want to be involved. METHODS AND MATERIALS: This prospective study involved 150 patients with localized prostate cancer treated with three-dimensional conformal radiotherapy. A decision aid was used to explain the effects of two alternative radiation doses (70 and 74 Gy) in terms of cure and side effects. Patients were then asked whether they wanted to choose their treatment (accept choice), or leave the decision to the physician (decline choice). The treatment preference was carried out. RESULTS: Even in this older population (mean age, 70 years), most patients (79%) accepted the option to choose. A lower score on the designations Pre-existent bowel morbidity, Anxiety, Depression, Hopelessness and a higher score on Autonomy and Numeracy were associated with an increase in choice acceptance, of which only Hopelessness held up in multiple regression (p < 0.03). The uninformed participation preference at baseline was not significantly related to choice acceptance (p = 0.10). CONCLUSION: Uninformed participation preference does not predict choice behavior. However, once the decision aid is provided, most patients want to choose their treatment. It should, therefore, be considered to inform patients first and ask participation preferences afterwards.

Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT.

PURPOSE: A higher radiation dose is believed to result in a larger probability of tumor control and a higher risk of side effects. To make an evidence-based choice of dose, the relation between dose and outcome needs to be known. This study focuses on the dose-response relation for prostate cancer. METHODS AND MATERIALS: A systematic review was carried out on the literature from 1990 to 2003. From the selected studies, the radiation dose, the associated 5-year survival, 5-year bNED (biochemical no evidence of disease), acute and late gastrointestinal (GI) and genitourinary (GU) morbidity Grade 2 or more, and sexual dysfunction were extracted. With logistic regression models, the relation between dose and outcome was described. RESULTS: Thirty-eight studies met our criteria, describing 87 subgroups and involving up to 3000 patients per outcome measure. Between the (equivalent) dose of 70 and 80 Gy, various models estimated an increase in 5-year survival (ranging from 10% to 11%), 5-year bNED for low-risk patients (5-7%), late GI complications (12-16%), late GU complications (8-10%), and erectile dysfunction (19-24%). Only for the overall 5-year bNED, results were inconclusive (range, 0-18%). CONCLUSIONS: The data suggest a relationship between dose and outcome measures, including survival. However, the strength of these conclusions is limited by the sometimes small number of studies, the incompleteness of the data, and above all, the correlational nature of the data. Unambiguous proof for the dose-response relationships can, therefore, only be obtained by conducting randomized trials.