- Informacje o czasopiśmie
- Format
- Czasopismo
- eISSN
- 1581-3207
- Pierwsze wydanie
- 30 Apr 2007
- Częstotliwość wydawania
- 4 razy w roku
- Języki
- Angielski
Prostate cancer can be treated by external beam radiotherapy (EBRT) brachyradiotherapy or radical prostatectomy; for low-risk disease and highly selected intermediate disease, active surveillance can be offered.1, 2, 3, 4, 5 Important factors in patient decision making are, therefore, the duration of treatment, circumstances of treatment, and treatment-induced side effects. Regarding side effects in EBRT, the use of intensity-modulated radiotherapy (IMRT) has been shown to reduce treatment-associated side effects compared with 3D-conformal radiotherapy.6,7 Further reduction of side effects is expected using image-guided radiotherapy (IGRT)8, in which fiducials, ultrasound, MRI, CT scans, or electromagnetic responders are used to locate the prostate before and during radiotherapy.9 However, to our knowledge, there are as yet no data regarding IGRT in the form of randomized controlled trials, although IGRT is recommended by the NCCN1, EAU5, British NICE10, and German S34 guidelines.
With this paper, we explore the role of gold fiducial markers (GFM) used for IGRT in primary prostate cancer treatment. There are only a few studies comparing patients with and without GFM. For example, a retrospective study by Zelefsky
In our department, we use cone-beam CT scans and ExacTrac (Brainlab, Munich, Germany), as well as routinely implanted GFM for image guidance. As GFM are implanted with the use of anesthesia, the benefit of the GFM has to be larger than the risks from anesthesia, including, but not limited to, nausea, allergic reactions, intraoperative awareness, or death16,17, and the risk of the intervention itself, such as infections or injuries to adjacent organs. Local anaesthesia reduces the risks of anaesthesia. Some patients have contraindications against anesthesia or refuse the intervention. A more precise patient positioning due to GFM can be expected to lead to greater treatment precision and hence, possibly, to reduced toxicity and increased tumor control. These assumed benefits can justify its routine application in patients with prostate cancer. Without these advantages, the routine use of GFM would not be justified. Therefore, we wanted to compare a group of patients receiving IGRT with GFM with a group receiving only IGRT to evaluate the potential benefits of GFM regarding tumor control and GI and GU toxicity.
Our study protocol was approved by the ethical review board of our university according to local regulations (EK Nr: 1533/2020). We included all patients between 2010 and 2015 with localized primary prostate cancer treated with EBRT by the use of volumetric modulated arc therapy (VMAT) with or without GFM implantation. Patients treated before 2010 were excluded, as routinely prescribed doses were below the currently recommended 75.6 Gy with 1.8 Gy per fraction.1 Due to the implementation of moderate hypofractionation in our department, patients treated after 2015 were excluded to keep the fractionation uniform among patients. The stage had to be cN0/x and cM0/x, with a risk of lymph node involvement < 15% according to the Roach formula18, and a clinical T category of 1 or 2.
Target volumes were defined using CT and MRI for planning. The prescribed doses were 78 Gy with 2 Gy per fraction. Doses were prescribed to 95% of the planning target volume (PTV) according to International Commission on Radiation Units and Measurements report 83.19 Safety margins were 7 mm after GFM implantation and 10 mm without. Irradiation was performed with the patient in supine position. All patients received a rectal balloon20 for prostate immobilization. Cone-beam CT control scans were performed daily for the first week, followed by daily ExacTrac (Brainlab, Munich, Germany) controls for the rest of treatment. The clinical target volume (CTV) included the prostate for low-risk tumors and additionally the base of the seminal vesicles for intermediate-risk tumors.
GFM implantation was recommended to all patients. Reasons for not receiving GFM were contraindications against anesthesia, such as pre-existing pulmonary illness, coronary heart disease, or myocardial infarction, or refusal by the patient. Implantation itself was performed transperineally with ultrasound guidance by the radiation oncologist, under mask narcosis performed by an anaesthesiologist. In each patient, 3 GFM were implanted, one on each side of the prostate and one in the apex. Ciprofloxacin 250 mg 1-0-1 was prescribed as postinterventional prophylaxis for 5 days. If patients received androgen deprivation therapy, it was prescribed by the caretaking urologist.
Patient follow-ups were immediately after treatment, 3 months after treatment, 12 months after treatment, and every 12 months from then on. At each follow-up, PSA levels and GI and GU side effects were assessed by the physician. bNED failure was defined using the Phoenix criteria (PSA nadir + 2 ng/mL).21 Acute and late GI and GU side effects were assessed using the RTOG criteria.22 Survival data were collected using the local death registry.
Dose-volume histogram (DVH) data were collected using our database. They included the volumes, Dmax/D1, and Dmean of the CTV, PTV, rectum, and bladder, as well as the Dmin of the CTV and the V70 and V60 for the rectum and V70, V50, and V30 for the bladder, as these data were used for plan evaluation.
The statistical analysis was performed using GraphPad Prism 9.3.1 (GraphPad Software, San Diego, CA, USA) and SPSS 28.0.1.0 (IBM, Armonk, NY, USA). A p-value of < 0.05 was considered statistically significant. bNED, overall survival, and disease-free survival were compared using the Kaplan-Meier method. Side effects were analyzed by use of the Mann-Whitney U test, the Kruskal-Wallis test, and a Cox regression analysis for the onset of late toxicity grade 2 or higher, as well as bNED and overall survival.
Patient characteristics are displayed in Table 1. We also analyzed the reasons for patients not receiving GFM implantation. Among them, most patients (12, 60%) had medical contraindications for anesthesia, 5 patients (25%) refused GFM implantation, and for 3 patients (15%) who did not receive GFM, the reason was unknown.
Patient characteristics
| n | 41 | 100% | 20 | 100% |
| 1 | 23 | 56% | 16 | 80% |
| 2 | 18 | 44% | 4 | 20% |
| iPSA in μg/l, median (IQR) | 7 (5.3/8.7) | 5.9 (4.4/10.6) | ||
| 6 | 26 | 63% | 18 | 90% |
| 7a | 12 | 29% | 1 | 5% |
| 7b | 3 | 7% | 1 | 5% |
| Low risk | 16 | 39% | 10 | 50% |
| Intermediate risk | 25 | 61% | 10 | 50% |
| ADT prescribed | 14 | 34% | 3 | 15% |
| Median duration of ADT in months (IQR) | 9 (3/18) | 6 (6/8) | ||
| Median age at RT (IQR) | 74 (70/77) | 72 (67/72) | ||
| Median follow-up in months (IQR) | 72 (49/84) | 68 (36/86.5) |
ADT = androgen deprivation therapy; cT = clinical tumor extension; GFM = gold fiducial markers; iPSA = initial prostate-specific antigen; IQR = interquartile range; RT = radiotherapy low risk = PSA < 10 μg/L and Gleason Score 6; intermediate risk = PSA ≥ 10 μg/L or Gleason Score 7a/b
bNED rates are displayed in Figure 1. bNED ratios after 5 years for patients with and without GFM implantation were 92% and 100%, respective-
Figure 1
Biochemical no evidence of disease (bNED) rates of patients with and without gold fiducial marker (GMF) implantation (p = 0.61).
ly. After 8 years, bNED rates were 87% and 86%, respectively (p = 0.61). We also analyzed disease-specific survival (DSS) and overall survival (OS). Regarding DSS, we did not find a single death due to prostate cancer (p > 0.9999). For OS, survival proportions for patients with and without GFM after 5 years were 93% and 95%, and after 8 years 90% and 95% (p = 0.56).
Maximum acute and late gastrointestinal side effects are displayed in Tables 2 and 3. No significant differences between the two groups were detected. It is noteworthy that at no point was a grade 4 toxicity detected. We also compared late GI and GU toxicity in the two groups after 3, 12, 24, 36, 48, 60, 72, 84, and 96 months, and did not find a significant difference at any point.
Maximum acute side effects in patients with and without gold fiducial marker implantation
| 0 | 27% | 15% | 17% | 5% |
| 1 | 66% | 65% | 44% | 55% |
| 2 | 7% | 20% | 39% | 40% |
No significant differences for acute gastrointestinal and genitourinary side effects were detected (p = 0.15 and p = 0.58, respectively).
Maximum late side effects in patients with and without gold fiducial marker implantation
| 0 | 59% | 50% | 37% | 35% |
| 1 | 12% | 15% | 27% | 25% |
| 2 | 24% | 35% | 34% | 35% |
| 3 | 5% | 0% | 2% | 5% |
No significant differences for late gastrointestinal and genitourinary side effects were detected (p = 0.64 and p = 0.80, respectively).
For DVH data, we started by comparing the two groups regarding volumes, Dmax/D1, and Dmean of the CTV, PTV, rectum, and bladder, as well as the Dmin of the CTV and the V70 and V60 for the rectum and V70, V50, and V30 for the bladder. Significant differences were found in the PTV (median 124.7 cm3with GFM and 157.1 cm3 without, p = 0.004), the Dmin of the CTV (median 76.0 Gy with GFM and 76.5 Gy without, p = 0.04), the rectal Dmean (median 36.0 Gy with GFM and 39.3 Gy without, p = 0.01), V70 (median 11.4 Gy with GFM and 16.1 Gy without, p < 0.001), and V60 (median 20.0 Gy with GFM and 25.3 Gy without, p < 0.001). An overview of the DVH data is presented in Table 4.
Dose-volume histograms for patients with and without gold fiducial markers (GFM)
| PTV prostate cm3median (IQR) | 124.72 (98.68–152.83) | 157.12 (128.34–173.66) |
| PTV Dmax/D1 median (IQR) | 81.55 (80.55 – 82.75) | 81.15 (80.46–82.06) |
| PTV Dmean median (IQR) | 78.10 (77.41–78.70) | 78.10 (77.00–78.43) |
| CTV prostate cm3median (IQR) | 44.14 (34.75– 64.70) | 43.91 (34.40– 55.42) |
| CTV Dmax/D1 median (IQR) | 81.24 (80.64– 82.57) | 81.22 (80.35– 81.85) |
| CTV Dmean median (IQR) | 78.58 (77.97–79.47) | 78.63 (77.94–79.04) |
| CTV Dmin median (IQR) | 76.00 (75.36–76.32) | 76.49 (75.88–77.05) |
| Rectal volume median (IQR) | 113.02 (100.22–134.55) | 114.53 (105.57–136.38) |
| Rectal Dmax median (IQR) | 80.06 (78.88– 81.98) | 80.24 (79.23–81.25) |
| Rectal Dmean median (IQR) | 35.99 (32.94–39.61) | 39.30 (37.81–42.99) |
| Rectal V70 Gy % median (IQR) | 11.41 (9.41–13.04) | 16.12 (14.55–18.66) |
| Rectal V70 Gy cm3median (IQR) | 13.21 (11.33–15.93) | 18.66 (16.55–21.39) |
| Rectal V60 Gy % median (IQR) | 19.95 (16.39–22.37) | 25.25 (23.77–29.26) |
| Rectal V60 Gy cm3median (IQR) | 23.36 (19.93–25.98) | 29.23 (26.74–33.13) |
| Bladder volume median (IQR) | 196.93 (113.66–282.94) | 155.76 (127.30–296.44) |
| Bladder Dmax/D1 median (IQR) | 78.78 (77.01–80.53) | 79.53 80.44(77.04) – |
| Bladder Dmean median (IQR) | 21.11 (16.92–30.06) | 28.10 (18.99–35.20) |
| Bladder V70 Gy % median (IQR) | 7.50 (5.44–11.78) | 9.43 (6.06–14.02) |
| Bladder (IQR) V70 Gy cm3median | 14.14 (10.53–21.16) | 19.01 (12.00–22.20) |
| Bladder V50 Gy % median (IQR) | 17.14 (12.00–26,40) | 20.81 30.86(13.60) – |
| Bladder (IQR) V50 Gy cm3median | 34.00 (23.17–42.23) | 37.58 (27.16–44.42) |
| Bladder V30 Gy % median (IQR) | 28.24 (21.74–41.73) | 41.31 (25.78–51.83) |
| Bladder V30 Gy cm3median (IQR) | 58.71 (43.43– 78.57) | 65.38 (48.97–83.61) |
CTV = clinical target volume; GFM = gold fiducial marker; IQR = interquartile range; PTV = planning target volume; RT = radiotherapy
We also performed a univariable, and if more than one variable was significant, a multivariable Cox regression analysis regarding bNED and OS, as displayed in Table 5, as well as the onset of late GI or GU toxicity grade 2 or higher. The results of our Cox regression analysis regarding bNED and OS are displayed in Table 5.
Uni- and multivariable Cox regression of biochemical no evidence of disease (bNED) and overall survival (OS)
| Use of GFM | 0.603 | 1.788 | 0.200–16.018 | - | - | - |
| Age at RT | 0.960 | 0.996 | 0.857–1.157 | - | - | - |
| PTV prostate | 0.789 | 1.003 | 0.980–1.027 | - | - | - |
| PTV Dmax/D1 | 0.556 | 1.133 | 0.747–1.719 | - | - | - |
| PTV Dmean | 0.960 | 0.978 | 0.410–2.332 | - | - | - |
| CTV prostate | 0.006 | 1.020 | 1.006–1.035 | 0.862 | 0.996 | 0.947–1.046 |
| CTV Dmax/D1 | 0.014 | 0.814 | 0.690–0.960 | 0.224 | 2.583 | 0.560–11.925 |
| CTV Dmean | 0.005 | 0.858 | 0.770–0.956 | 0.298 | 0.188 | 0.008–4.393 |
| CTV Dmin | 0.005 | 0.875 | 0.797–0.960 | 0.453 | 2.067 | 0.310–13.770 |
| Use of GFM | 0.564 | 1.907 | 0.213–17.063 | - | - | - |
| Age at RT | 0.235 | 1.149 | 0.913–1.446 | - | - | - |
| PTV Prostate | 0.723 | 1.004 | 0.984–1.024 | - | - | - |
| PTV Dmax/D1 | 0.300 | 0.705 | 0.364–1.366 | - | - | - |
| PTV Dmean | 0.153 | 0.426 | 0.132–1.373 | - | - | - |
| CTV Prostate | 0.833 | 1.002 | 0.980–1.025 | - | - | - |
| CTV Dmax/D1 | 0.775 | 0.964 | 0.747–1.242 | - | - | - |
| CTV Dmean | 0.946 | 0.992 | 0.791–1.245 | - | - | - |
| CTV Dmin | 0.879 | 1.024 | 0.758–1.383 | - | - | - |
bNED = biochemical no evidence of disease; CTV = clinical target volume; GFM = gold fiducial marker; HR = hazard ratio; OS = overall survival; PTV = planning target volume; RT = radiotherapy
As no patient died of prostate cancer, we did not model a Cox regression for DSS. Analyses including rectal or bladder DVH variables regarding bNED and OS were performed, and none of the variables was significant. Therefore, to improve clarity, we did not add them to Table 5. The results regarding toxicity are displayed in Table 6.
Uni- and multivariable Cox regression of the onset of late gastrointestinal or genitourinary toxicity grade 2 or higher
| Use of GFM | 0.89 | 0.936 | 0.368–2.378 | - | - | - |
| Acute GI grade 2 | 0.09 | 2.642 | 0.875–7.981 | - | - | - |
| Age at RT | 0.03 | 1.124 | 1.010–1.252 | 0.101 | 1.092 | 0.983-1.213 |
| PTV prostate | 0.06 | 0.987 | 0.974–1.000 | - | - | - |
| PTV Dmax/D1 | 0.76 | 1.037 | 0.824–1.305 | - | - | - |
| PTV Dmean | 0.49 | 1.158 | 0.767–1.747 | - | - | - |
| CTV prostate | 0.03 | 0.966 | 0.936–0.996 | 0.073 | 0.972 | 0.942–1.003 |
| CTV Dmax/D1 | 0.55 | 1.056 | 0.884–1.263 | - | - | - |
| CTV Dmean | 0.51 | 1.090 | 0.843–1.410 | - | - | - |
| CTV Dmin | 0.64 | 1.042 | 0.877–1.236 | - | - | - |
| Rectal Volume | 0.29 | 1.007 | 0.994–1.020 | - | - | - |
| Rectal Dmax | 0.29 | 1.125 | 0.906–1.397 | - | - | - |
| Rectal Dmean | 0.25 | 0.951 | 0.973–1.036 | - | - | - |
| Rectal V70 Gy % | 0.59 | 0.971 | 0.875–1.078 | - | - | - |
| Rectal V70 Gy cm3 | 0.42 | 1.040 | 0.945–1.144 | - | - | - |
| Rectal V60 Gy % | 0.42 | 0.969 | 0.899–1.046 | - | - | - |
| Rectal V60 Gy cm3 | 0.50 | 1.024 | 0.955–1.099 | - | - | - |
| Use of GFM | 0.93 | 1.041 | 0.441–2.459 | - | - | - |
| Acute GU grade 2 | 0.09 | 2.042 | 0.892–4.673 | - | - | - |
| Age at RT | 0.50 | 1.026 | 0.952–1.106 | - | - | - |
| PTV prostate | 0.29 | 1.006 | 0.995–1.017 | - | - | - |
| PTV Dmax/D1 | 0.14 | 0.808 | 0.611–1.068 | - | - | - |
| PTV Dmean | 0.04 | 0.573 | 0.342–0.961 | - | - | - |
| CTV prostate | 0.93 | 0.999 | 0.989–1.010 | - | - | - |
| CTV Dmax/D1 | 0.93 | 1.006 | 0.895–1.130 | - | - | - |
| CTV Dmean | 0.67 | 1.025 | 0.916–1.147 | - | - | - |
| CTV Dmin CTV | 0.58 | 1.035 | 0.918–1.165 | - | - | - |
| Bladder volume | 0.72 | 0.999 | 0.997–1.002 | - | - | - |
| Bladder Dmax/D1 | 0.24 | 0.973 | 0.696–1.094 | - | - | - |
| Bladder Dmean | 0.89 | 0.997 | 0.960–1.036 | - | - | – |
| Bladder V70 Gy % | 0.49 | 0.977 | 0.913–1.045 | - | - | - |
| Bladder V70 Gy cm3 | 0.23 | 0.969 | 0.921–1.020 | - | - | - |
| Bladder V50 Gy % | 0.54 | 0.988 | 0.951–1.027 | - | - | - |
| Bladder V50 Gy cm3 | 0.29 | 0.985 | 0.957–1.013 | - | - | - |
| Bladder V30 Gy % | 0.79 | 0.997 | 0.974–1.020 | - | - | - |
| Bladder V30 Gy cm3 | 0.70 | 0.997 | 0.980–1.014 | - | - | - |
CTV = clinical target volume; GFM = gold fiducial marker; GI = gastrointestinal; GU = genitourinary; PTV = planning target volume; RT = radiotherapy
As GFM implantation is an invasive procedure, the benefits of implantation have to outweigh the potential risks. There are two categories of risks. The first is the risk due to the implantation itself. Citing our information sheet, these risks are bleeding, injuries of the bladder and urethra, infection including abscess formation, and allergic reactions to the prescribed antibiotic. The second category is risks due to the anaesthesia. Even when only a breathing mask is used to administer anaesthesia, these risks include tissue damage due to patient positioning, allergic reactions, malignant hyperthermia, subsequent confusion, aspiration, and regaining consciousness during anesthesia.16,17 While these side effects occur rarely in our clinical experience, as well as in the literature23, they have to be considered in evaluating GFM implantation, aside from its influence on tumor control and side effects.
Several retrospective studies comparing fiducial IGRT with a control group exist. However, most of them compare a 3D conformal group with either an IGRT 3D conformal group14,24 or an IGRT IMRT group12, making them hard to apply to today’s treatment due to their being outdated or their comparison of two different treatment modalities with inherent differences regarding outcomes. While many international guidelines1,4,10 suggest the use of IGRT, no study covering this topic is mentioned in the NCCN1 or NICE10 guidelines. Napieralska
It is quite likely that the most crucial effect regarding potential outcomes in our department is the safety margin reduction by 3 mm in GFM patients, which is absent from the aforementioned studies. The effect of reducing the safety margin by 3 mm can be displayed using math. Assume a spherical form for the prostate, with a radius between 2 and 2.5 cm and safety margins of 7 mm and 10 mm. The radii, including the PTV safety margins, are 2.7 cm and 3 cm, with an initial radius of 2 cm and 3.2 cm, respectively, and 3.5 cm with an initial radius of 2.5 cm. With 4/3*π*r3 being the formula for the volume of a sphere, reducing the safety margins by 3 mm leads to a decrease in the PTV of 27% for the 2-cm initial radius and 24% for the 2.5-cm initial radius (2.73/33and 3.23/3.53). In our data, the difference in the median volume is 21%, similar to the expected difference. Although this calculation is far from perfect, as the prostate is not a perfect sphere, it allows one to imagine the effect of safety margin variation through the third power of the radius. Zelefsky’s conclusion in his IGRT study11 was that safety margins should be reduced. However, to our knowledge, he has yet to publish any data comparing bNED rates before and after margin reduction.
When comparing our bNED rates with those of groundbreaking studies like those of Peeters
One weakness of our study is its retrospective nature. On top of that, there is no group of patients with GFM implantation and a safety margin of 10
mm, complicating the direct comparison of our two groups, as GFM were implanted and the safety margin was reduced to 7 mm together. However, retrospective studies should be used to generate hypotheses, not prove them, and with this study we have generated the hypothesis that the use of GFM for IGRT provides no benefits, but only risks, and should not be performed regularly if other, non-invasive tools for IGRT are in use. Another weakness is the limited sample size.
Regarding strengths, we analyzed a homogeneous patient collective to address this question, with in-depth data including bNED, OS, DSS, and acute and late toxicity, as well as DVH data. Besides, our patient collectives were recruited in parallel, and this reduced any potential bias due to changing treatment modalities over time.
With this study, we have developed the hypothesis that the use of GFM in IGRT does not provide a substantial benefit regarding tumor control or toxicity when other modalities for IGRT are used. To clarify the role of GFM in IGRT, prospective studies based on this hypothesis are needed to possibly reduce the number of unnecessary medical interventions in the treatment of men’s most common cancer.
Figure 1
Maximum late side effects in patients with and without gold fiducial marker implantation
| 0 | 59% | 50% | 37% | 35% |
| 1 | 12% | 15% | 27% | 25% |
| 2 | 24% | 35% | 34% | 35% |
| 3 | 5% | 0% | 2% | 5% |
Dose-volume histograms for patients with and without gold fiducial markers (GFM)
| PTV prostate cm |
124.72 (98.68–152.83) | 157.12 (128.34–173.66) |
| PTV Dmax/D1 median (IQR) | 81.55 (80.55 – 82.75) | 81.15 (80.46–82.06) |
| PTV Dmean median (IQR) | 78.10 (77.41–78.70) | 78.10 (77.00–78.43) |
| CTV prostate cm |
44.14 (34.75– 64.70) | 43.91 (34.40– 55.42) |
| CTV Dmax/D1 median (IQR) | 81.24 (80.64– 82.57) | 81.22 (80.35– 81.85) |
| CTV Dmean median (IQR) | 78.58 (77.97–79.47) | 78.63 (77.94–79.04) |
| CTV Dmin median (IQR) | 76.00 (75.36–76.32) | 76.49 (75.88–77.05) |
| Rectal volume median (IQR) | 113.02 (100.22–134.55) | 114.53 (105.57–136.38) |
| Rectal Dmax median (IQR) | 80.06 (78.88– 81.98) | 80.24 (79.23–81.25) |
| Rectal Dmean median (IQR) | 35.99 (32.94–39.61) | 39.30 (37.81–42.99) |
| Rectal V70 Gy % median (IQR) | 11.41 (9.41–13.04) | 16.12 (14.55–18.66) |
| Rectal V70 Gy cm |
13.21 (11.33–15.93) | 18.66 (16.55–21.39) |
| Rectal V60 Gy % median (IQR) | 19.95 (16.39–22.37) | 25.25 (23.77–29.26) |
| Rectal V60 Gy cm |
23.36 (19.93–25.98) | 29.23 (26.74–33.13) |
| Bladder volume median (IQR) | 196.93 (113.66–282.94) | 155.76 (127.30–296.44) |
| Bladder Dmax/D1 median (IQR) | 78.78 (77.01–80.53) | 79.53 80.44(77.04) – |
| Bladder Dmean median (IQR) | 21.11 (16.92–30.06) | 28.10 (18.99–35.20) |
| Bladder V70 Gy % median (IQR) | 7.50 (5.44–11.78) | 9.43 (6.06–14.02) |
| Bladder (IQR) V70 Gy cm |
14.14 (10.53–21.16) | 19.01 (12.00–22.20) |
| Bladder V50 Gy % median (IQR) | 17.14 (12.00–26,40) | 20.81 30.86(13.60) – |
| Bladder (IQR) V50 Gy cm |
34.00 (23.17–42.23) | 37.58 (27.16–44.42) |
| Bladder V30 Gy % median (IQR) | 28.24 (21.74–41.73) | 41.31 (25.78–51.83) |
| Bladder V30 Gy cm |
58.71 (43.43– 78.57) | 65.38 (48.97–83.61) |
Uni- and multivariable Cox regression of the onset of late gastrointestinal or genitourinary toxicity grade 2 or higher
| Use of GFM | 0.89 | 0.936 | 0.368–2.378 | - | - | - |
| Acute GI grade 2 | 0.09 | 2.642 | 0.875–7.981 | - | - | - |
| Age at RT | 0.03 | 1.124 | 1.010–1.252 | 0.101 | 1.092 | 0.983-1.213 |
| PTV prostate | 0.06 | 0.987 | 0.974–1.000 | - | - | - |
| PTV Dmax/D1 | 0.76 | 1.037 | 0.824–1.305 | - | - | - |
| PTV Dmean | 0.49 | 1.158 | 0.767–1.747 | - | - | - |
| CTV prostate | 0.03 | 0.966 | 0.936–0.996 | 0.073 | 0.972 | 0.942–1.003 |
| CTV Dmax/D1 | 0.55 | 1.056 | 0.884–1.263 | - | - | - |
| CTV Dmean | 0.51 | 1.090 | 0.843–1.410 | - | - | - |
| CTV Dmin | 0.64 | 1.042 | 0.877–1.236 | - | - | - |
| Rectal Volume | 0.29 | 1.007 | 0.994–1.020 | - | - | - |
| Rectal Dmax | 0.29 | 1.125 | 0.906–1.397 | - | - | - |
| Rectal Dmean | 0.25 | 0.951 | 0.973–1.036 | - | - | - |
| Rectal V70 Gy % | 0.59 | 0.971 | 0.875–1.078 | - | - | - |
| Rectal V70 Gy cm |
0.42 | 1.040 | 0.945–1.144 | - | - | - |
| Rectal V60 Gy % | 0.42 | 0.969 | 0.899–1.046 | - | - | - |
| Rectal V60 Gy cm |
0.50 | 1.024 | 0.955–1.099 | - | - | - |
| Use of GFM | 0.93 | 1.041 | 0.441–2.459 | - | - | - |
| Acute GU grade 2 | 0.09 | 2.042 | 0.892–4.673 | - | - | - |
| Age at RT | 0.50 | 1.026 | 0.952–1.106 | - | - | - |
| PTV prostate | 0.29 | 1.006 | 0.995–1.017 | - | - | - |
| PTV Dmax/D1 | 0.14 | 0.808 | 0.611–1.068 | - | - | - |
| PTV Dmean | 0.04 | 0.573 | 0.342–0.961 | - | - | - |
| CTV prostate | 0.93 | 0.999 | 0.989–1.010 | - | - | - |
| CTV Dmax/D1 | 0.93 | 1.006 | 0.895–1.130 | - | - | - |
| CTV Dmean | 0.67 | 1.025 | 0.916–1.147 | - | - | - |
| CTV Dmin CTV | 0.58 | 1.035 | 0.918–1.165 | - | - | - |
| Bladder volume | 0.72 | 0.999 | 0.997–1.002 | - | - | - |
| Bladder Dmax/D1 | 0.24 | 0.973 | 0.696–1.094 | - | - | - |
| Bladder Dmean | 0.89 | 0.997 | 0.960–1.036 | - | - | – |
| Bladder V70 Gy % | 0.49 | 0.977 | 0.913–1.045 | - | - | - |
| Bladder V70 Gy cm |
0.23 | 0.969 | 0.921–1.020 | - | - | - |
| Bladder V50 Gy % | 0.54 | 0.988 | 0.951–1.027 | - | - | - |
| Bladder V50 Gy cm |
0.29 | 0.985 | 0.957–1.013 | - | - | - |
| Bladder V30 Gy % | 0.79 | 0.997 | 0.974–1.020 | - | - | - |
| Bladder V30 Gy cm |
0.70 | 0.997 | 0.980–1.014 | - | - | - |
Maximum acute side effects in patients with and without gold fiducial marker implantation
| 0 | 27% | 15% | 17% | 5% |
| 1 | 66% | 65% | 44% | 55% |
| 2 | 7% | 20% | 39% | 40% |
Uni- and multivariable Cox regression of biochemical no evidence of disease (bNED) and overall survival (OS)
| Use of GFM | 0.603 | 1.788 | 0.200–16.018 | - | - | - |
| Age at RT | 0.960 | 0.996 | 0.857–1.157 | - | - | - |
| PTV prostate | 0.789 | 1.003 | 0.980–1.027 | - | - | - |
| PTV Dmax/D1 | 0.556 | 1.133 | 0.747–1.719 | - | - | - |
| PTV Dmean | 0.960 | 0.978 | 0.410–2.332 | - | - | - |
| CTV prostate | 0.006 | 1.020 | 1.006–1.035 | 0.862 | 0.996 | 0.947–1.046 |
| CTV Dmax/D1 | 0.014 | 0.814 | 0.690–0.960 | 0.224 | 2.583 | 0.560–11.925 |
| CTV Dmean | 0.005 | 0.858 | 0.770–0.956 | 0.298 | 0.188 | 0.008–4.393 |
| CTV Dmin | 0.005 | 0.875 | 0.797–0.960 | 0.453 | 2.067 | 0.310–13.770 |
| Use of GFM | 0.564 | 1.907 | 0.213–17.063 | - | - | - |
| Age at RT | 0.235 | 1.149 | 0.913–1.446 | - | - | - |
| PTV Prostate | 0.723 | 1.004 | 0.984–1.024 | - | - | - |
| PTV Dmax/D1 | 0.300 | 0.705 | 0.364–1.366 | - | - | - |
| PTV Dmean | 0.153 | 0.426 | 0.132–1.373 | - | - | - |
| CTV Prostate | 0.833 | 1.002 | 0.980–1.025 | - | - | - |
| CTV Dmax/D1 | 0.775 | 0.964 | 0.747–1.242 | - | - | - |
| CTV Dmean | 0.946 | 0.992 | 0.791–1.245 | - | - | - |
| CTV Dmin | 0.879 | 1.024 | 0.758–1.383 | - | - | - |
Patient characteristics
| n | 41 | 100% | 20 | 100% |
| 1 | 23 | 56% | 16 | 80% |
| 2 | 18 | 44% | 4 | 20% |
| iPSA in μg/l, median (IQR) | 7 (5.3/8.7) | 5.9 (4.4/10.6) | ||
| 6 | 26 | 63% | 18 | 90% |
| 7a | 12 | 29% | 1 | 5% |
| 7b | 3 | 7% | 1 | 5% |
| Low risk | 16 | 39% | 10 | 50% |
| Intermediate risk | 25 | 61% | 10 | 50% |
| ADT prescribed | 14 | 34% | 3 | 15% |
| Median duration of ADT in months (IQR) | 9 (3/18) | 6 (6/8) | ||
| Median age at RT (IQR) | 74 (70/77) | 72 (67/72) | ||
| Median follow-up in months (IQR) | 72 (49/84) | 68 (36/86.5) |