Why Do Men Reject Adjuvant Radiotherapy following Radical Prostatectomy? A Systematic Survey.

INTRODUCTION: The aim of this study was to investigate non-adherence rates to adjuvant radiotherapy (aRT) after radical prostatectomy (RP) and to obtain patient reported reasons for rejecting aRT despite recommendation by a multidisciplinary team discussion (MTD). METHODS: In a retrospective monocentric analysis, we identified 1,197 prostate cancer patients who underwent RP between 2014 and 2022 at our institution, of which 735 received a postoperative MTD recommendation. Patients with a recommendation for aRT underwent a structured phone interview with predefined standardised qualitative and quantitative questions and were stratified into "adherent" (aRT performed) and "non-adherent" groups (aRT not performed). RESULTS: Of 55 patients receiving a recommendation for aRT (7.5% of all RP patients), 24 (44%) were non-adherent. Baseline tumour characteristics were comparable among the groups. "Fear of radiation damage" was the most common reason for rejection, followed by "lack of information," "feeling that the treating physician does not support the recommendation" and "the impression that aRT is not associated with improved oncological outcome." Salvage radiotherapy was performed in 25% of non-adherent patients. CONCLUSION: High rates of non-adherence to aRT after RP were observed, and reasons for this phenomenon are most likely multifactorial. Multidisciplinary and individualized patient counselling might be a key for increasing adherence rates.

Salvage radiotherapy for macroscopic local recurrences after radical prostatectomy : A national survey on patterns of practice.

INTRODUCTION: Although salvage radiotherapy (SRT) for PSA recurrence after radical prostatectomy provides better oncological outcomes when delivered early, in the absence of detectable disease many patients are treated for macroscopic locally recurrent tumors. Due to limited data from prospective studies, we hypothesized an important variability in the SRT management of these patients. Our aim was to investigate current practice patterns of SRT for local macroscopic recurrence after radical prostatectomy. MATERIAL AND METHODS: A total of 14 Swiss radiation oncology centers were asked to complete a survey on treatment specifications for macroscopic locally recurrent disease including information on pretherapeutic diagnostic procedures, dose prescription, radiation delivery techniques and androgen deprivation therapy (ADT). Treatment recommendations on ADT were analyzed using the objective consensus methodology. RESULTS: The majority of centers recommended pretreatment magnetic resonance imaging (MRI) of the pelvis and choline positron emission tomography (PET). The median prescribed dose to the prostate bed was 66 Gy (range 65-72 Gy) with a boost to the macroscopic lesion used by 79% of the centers with a median total dose of 72 Gy (range 70-80 Gy). Intensity-modulated rotational techniques were used by all centers and daily cone beam computed tomography (CT) was recommended by 43%. The use of concomitant ADT for any macroscopic recurrence was recommended by 43% of the centers while the remaining centers recommended it only for high-risk disease, which was not consistently defined. CONCLUSION: We observed a high variability of treatment paradigms when SRT is indicated for macroscopic local recurrences after prostatectomy. These data reflect the need for more standardized approaches and ultimately further research in this field.

Erectile function preservation after salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: Five-year results of the SAKK 09/10 randomized phase 3 trial.

Objectives: To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP). Materials and methods: Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT. Results: 344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm. Conclusion: ED after RP is a known long-term side effect with significant impact on patients' QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050.

Adherence to Contouring and Treatment Planning Requirements Within a Multicentric Trial: Results of the Quality Assurance of the SAKK 09/10 trial.

PURPOSE: To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy. METHODS AND MATERIALS: Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated. RESULTS: The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07). CONCLUSIONS: Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines.

Radiotherapy for pelvic nodal recurrences after radical prostatectomy: patient selection in clinical practice.

AIM: There is no general consensus on the optimal treatment for prostate cancer (PC) patients with intrapelvic nodal oligorecurrences after radical prostatectomy. Besides androgen deprivation therapy (ADT) as standard of care, both elective nodal radiotherapy (ENRT) and stereotactic body radiotherapy (SBRT) as well as salvage lymph node dissection (sLND) are common treatment options. The aim of our study was to assess decision making and practice patterns for salvage radiotherapy (RT) in this setting. METHODS: Treatment recommendations from 14 Swiss radiation oncology centers were collected and converted into decision trees. An iterative process using the objective consensus methodology was applied to assess differences and consensus. RESULTS: PSMA PET/CT was recommended by 93% of the centers as restaging modality. For unfit patients defined by age, comorbidities or low performance status, androgen deprivation therapy (ADT) alone was recommended by more than 70%. For fit patients with unfavorable tumor characteristics such as short prostate-specific antigen (PSA) doubling time or initial high-risk disease, the majority of the centers (57-71%) recommended ENRT + ADT for 1-4 lesions. For fit patients with favorable tumor characteristics, there were low levels of consensus and a wide variety of recommendations. For 1-4 nodal lesions, focal SBRT was offered by 64% of the centers, most commonly as a 5-fraction course. CONCLUSIONS: As an alternative to ADT, ENRT or SBRT for pelvic nodal oligorecurrences of PC are commonly offered to selected patients, with large treatment variations between centers. The exact number of lymph nodes had a major impact on treatment selection.

Compensating for tumor motion by a 6-degree-of-freedom treatment couch: is patient tolerance an issue?

PURPOSE: To determine whether patients could tolerate the motion of a robotic couch that compensates for breathing-induced tumor motion. METHODS AND MATERIALS: A total of 10 healthy subjects and 23 radio-oncology patients underwent simulated extracranial stereotactic radiotherapy (two 30-min sessions) on a robotic couch programmed to follow a fictitious tumor trajectory of 20x5x5 mm (cranio-caudal, left-right, and anterior-posterior directions, respectively) while rotating 2 degrees around a cranio-caudal axis at a frequency of 5 seconds per loop. RESULTS: No session had to be interrupted and no nausea was induced. However, one patient refused the second session due to general deterioration and not all patients could keep their arms elevated for the entire session. CONCLUSIONS: Our findings showed that most patients tolerated compensatory couch motion and that motion sickness should not pose a problem in the investigation of this tumor-tracking method.

High-energy phosphate metabolism during two bouts of progressive calf exercise in humans measured by phosphorus-31 magnetic resonance spectroscopy.

According to the literature the steady-state level of phosphocreatine (PCr) has a linear relationship to the workload during muscle exercise intensities below the lactate threshold, whereas this linearity is impaired during exercise intensities above the lactate threshold. The purpose of this study was to investigate the linearity between PCr kinetics and workload during two bouts of isotonic incremental calf exercise with transitions from moderate- to high-intensity as well as from high- to moderate-intensity work rates. Using a whole-body 1.5 T MR scanner and a self-built exercise bench, we performed serial phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) with a time resolution of 30 s in nine healthy male volunteers. Changes in PCr, inorganic phosphate (Pi) and pH were statistically evaluated in comparison to the baseline. The exercise protocol started with a 4.5 W interval of 6 min followed by two bouts of 1.5 W increments. The workload was increased in 2-min intervals up to 9 W during the first bout and up to 7.5 W during the second bout. The second bout was preceded by a 4.5 W interval of 2 min and followed by a 4.5 W interval of 4 min. PCr hydrolysis achieved a steady state during each increment and was highly linear to the work rate (r (2), -0.796; P <0.001). Pi accumulated during each bout, whereas the pH decreased continuously during the first bout and did not exhibit any substantial decrease during the second bout. The metabolite levels and pH were expressed as the median value and the range. Our study confirms that steady-state PCr levels also have a linear relationship to work intensities above the lactate threshold, while pH changes do not have any impact on PCr degradation. The lack of substantial changes in pH during the second exercise bout indicates that prior high-intensity exercise leads to an activation of oxidative phosphorylation.

High-energy phosphate metabolism in the calf muscle during moderate isotonic exercise under different degrees of cuff compression: a phosphorus 31 magnetic resonance spectroscopy study.

BACKGROUND: The purpose of this study was to investigate phosphocreatine (PCr) and inorganic phosphate levels as well as pH changes in exercising muscle at a workload of 4.5 W under progressive cuff stenoses, whereby the flow reduction due to cuff compression was quantified by flow-sensitive magnetic resonance imaging. METHODS: By using a whole-body 1.5-T magnetic resonance scanner and an exercise bench, serial phosphorus 31 (31P) magnetic resonance spectroscopy with a time resolution of 30 seconds was performed in 10 healthy men. Percentage changes in PCr, inorganic phosphate (Pi), and pH were statistically evaluated in comparison with baseline. The exercise protocol was characterized by a constant workload level of 4.5 W. Ischemic conditions were achieved by a cuff that was placed at the upper leg. Consecutively, increments of 0, 60, 90, 120, and 150 mm Hg were applied. Each increment lasted for 3 minutes. The following rest period was 10 minutes. RESULTS: Blood flow increased significantly immediately after the onset of muscle exercise. No significant changes in blood flow were detected as long as the air pressure of the pneumatic cuff was 60 to 90 mm Hg. Significant reductions in blood flow were observed immediately after inflation of the cuff to 120 and 150 mm Hg. PCr passed into a steady state during the first increment with 0 mm Hg and showed no substantial changes during the increment with 60, 90, and 120 mm Hg. PCr hydrolysis seemed progressive during the 150-mm Hg increment. Pi passed into a plateau level at the onset of exercise and increased significantly at the increment of 150 mm Hg. The pH turned into a steady state with no significant changes during the increments up to 120 mm Hg. At 150 mm Hg, pH decreased progressively. PCr levels at the end of the 150-mm Hg increment correlated significantly and moderately with the reduction in blood flow. CONCLUSIONS: Our study shows that the ischemic condition during constant muscle exercise is clearly characterized by PCr and Pi kinetics, as well as by pH changes. The correlation between the degree of blood flow reduction and PCr levels in the exercising muscle groups, which are supplied by the stenosed arteries, is the first essential of using 31P magnetic resonance spectroscopy in the assessment of the effect of arterial stenoses on muscle function in claudicants.