Background
Definitive Radiation Therapy for clinically localized prostate cancer
Author, year | Ref | RT type | n | total dose (Gy) | total fractions | Gy/ fraction | PFS def. | Risk group n | 5-year PFS (%) | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
LR | IR | HR | LR | IR | HR | ||||||||
Kuban, 2008 | [6] | 3D | 151 | 78 | 39 | 2 | P | 30 | 68 | 53 | 100 | 86 | 69 |
3D | 150 | 70 | 35 | 2 | P | 31 | 71 | 48 | 88 | 83 | 54 | ||
Al-Mamgani, 2008 | [7] | 3D | 333 | 78 | 39 | 2 | P | 63 | 90 | 180 | N/A | 70 | N/A |
3D | 331 | 68 | 34 | 2 | P | 56 | 89 | 185 | N/A | 60 | N/A | ||
Zietman, 2010 | [8] | 3D | 195 | 79 | 44 | 1.8 | P | 116 | 72 | 7 | 95 | 79 | N/A |
3D | 197 | 70 | 39 | 1.8 | P | 111 | 76 | 10 | 75 | 68 | N/A | ||
Dearnaley, 2007 | [9] | 3D | 422 | 74 | 37 | 2 | P | 99 | 127 | 184 | 71 | 71 | N/A |
3D | 421 | 64 | 32 | 2 | P | 95 | 137 | 175 | 60 | 60 | N/A | ||
Michalski, 2010, 2012 | 3D | 108 | 68 | 38 | 1.8 | P | 55 | 37 | 69 | 68 | 70 | 42 | |
3D | 300 | 74 | 41 | 1.8 | P | 91 | 75 | 39 | 73 | 62 | 62 | ||
3D | 167 | 79 | 44 | 1.8 | P | 85 | 54 | 36 | 67 | 70 | 70 | ||
3D | 256 | 74 | 37 | 2 | P | 92 | 109 | 40 | 84 | 74 | 54 | ||
3D | 220 | 78 | 39 | 2 | P | 80 | 109 | 32 | 80 | 69 | 67 | ||
Beckendorf, 2011 | [12] | 3D | 153 | 70 | 35 | 2 | P | – | 153 | – | – | 68 | – |
3D | 153 | 80 | 40 | 2 | P | – | 153 | – | – | 74 | – | ||
Michalski, 2014 | [13] | 3D+ IMRT | 748 | 79 | 44 | 1.8 | P | – | 748 | – | – | 75 | – |
3D+ IMRT | 751 | 70 | 39 | 1.8 | P | – | 751 | – | – | 60 | – | ||
3D | (491) | N/A | N/A | N/A | P | 30 | 68 | 53 | N/A | N/A | N/A | ||
IMRT | (257) | N/A | N/A | N/A | P | 31 | 71 | 48 | N/A | N/A | N/A | ||
Lukka, 2005 | [14] | 3D | 470 | 66 | 33 | 2 | A | – | 470 | – | N/A | 53 | N/A |
3D | 466 | 52 | 20 | 2.63 | A | – | 466 | – | N/A | 60 | N/A | ||
Yeoh, 2011 | [15] | 3D | 109 | 64 | 32 | 2 | P | – | 109 | – | N/A | 58 | N/A |
3D | 108 | 55 | 20 | 2.75 | P | – | 108 | – | N/A | 69 | N/A | ||
Arcangeli, 2012 | [16] | 3D | 85 | 80 | 40 | 2 | P | – | – | 85 | N/A | N/A | 79 |
3D | 83 | 62 | 20 | 3.1 | P | – | – | 83 | N/A | N/A | 85 | ||
Pollack, 2013 | [17] | IMRT | 152 | 76 | 38 | 2 | P | – | 101 | 51 | N/A | 86 | 86 |
IMRT | 151 | 70 | 26 | 2.7 | P | – | 98 | 53 | N/A | 86 | 86 | ||
Kuban, 2010 | [18] | IMRT | 102 | 76 | 42 | 1.8 | P | 30 | 1 | 1 | 96 | 96 | N/A |
IMRT | 102 | 72 | 30 | 2.4 | P | 30 | 1 | 1 | 97 | 97 | N/A | ||
Mantz, 2014 | [19] | Gantry | 102 | 40 | 5 | 8.0 | P | 40 | – | – | 100 | N/A | N/A |
Katz, 2010, 2011 | RA | 304 | 35 | 5 | 7.0 | P | 211 | 81 | 12 | 99 | 93 | 75 | |
36 | 5 | 7.3 | P | ||||||||||
Fuller, 2014 | [22] | RA | 60 | 38 | 4 | 9.5 | P | 40 | 39 | – | 100 | 92 | N/A |
Dubray, 2016 | [23] | 3D without ADT | 191 | 80 | 40 | 2 | – | – | 191 | – | – | 76 | – |
with ADT | 179 | – | – | 179 | – | – | 84 | – | |||||
Dong, 2017 | [24] | 3D/IMRT without ADT | 979 | 74–80 or 70.2 | 40 or 26 | 1.8–2.7 | – | – | 979 | – | – | 87.3 | – |
with ADT | 155 | – | – | 155 | – | – | 84 | – |
Impact of PSMA PET/CT on primary staging of prostate Cancer
Author and year | Study Design | Location | N | Population | Median PSA ng/mL (range) | Improvement with PSMA PET |
---|---|---|---|---|---|---|
Budäus et al. 2016 [48] | R | Hamburg, Germany | 30 | HR PCa prior to RP | 8.8 (1.4–376) | Se 33%, spec 100%, PPV 100%, NPV 69% |
Calais et al. 2018 [45] | P | Los Angeles, USA | 73 | IR/HR PCa prior to RT planning | 13.9 (0.22–909) | 9.5% uptaged to M1 |
Demirkol et al. 2015 [49] | R | Istanbul, Turkey | 8 | HR PCa for staging | 15 (0.3–20) | N/A |
Fendler et al. 2016 [50] | R | Munich, Germany | 21 | PCa for staging | N/A | Se 67%, spec 92%, PPV 97%, NPV 42% Acc 72% |
Frenzel et al. 2018 [51] | R | Hamburg, Germany | 20 | PCa prior to RT planning | 7.1 (0.48–137) | N/A |
Herlemann et al. 2016 [52] | R | Munich, Germany | 20 | HR PCa prior to RP | a56 (3.3–363) | Se 84%, spec 82%, PPV 84%, NPV 82% |
Hijazi et al. 2015 [53] | R | Göttingen, Germany | 12 | PCa for staging | 48 (6–90) | Se 94%, spec 99%, PPV 89%, NPV 99.5% |
Hirmas et al. 2018 [54] | R | Amman, Jordan | 21 | HR PCa for staging | 38 (0.6- > 100) | Se 85% Acc 85.7%, PPV 100% |
Hruby et al. 2018 [55] | R | NSW, Australia | 109 | IR/HR PCa prior to EBRT | 9.9 (1.23–240) | 21% upstaged, 3% downstaged |
Kabasakal et al. 2015 [56] | R | Istanbul, Turkey | 15 | PCa for staging | 37.78 (5.12–70.47) | N/A |
Maurer et al. 2015 [57] | R | Munich, Germany | 130 | HR PCa prior to RP | 11.6 (0.57–244) | Se 68%, spec 99%, PPV 95%, NPV 94% |
Rahbar et al. 2015 [58] | P | Münster, Germany | 6 | HR PCa prior to RP | 52.7 (5.7–111.1) | Se 92%, spec 92%, PPV 96%, NPV 85% |
Rhee et al. 2016 [59] | P | Queensland, Australia | 20 | PCa prior to RP | 6.1 (3.5–45) | Se 49%, spec 95%, PPV 85% NPV 88% |
Roach et al. 2017 [44] | P | Sydney, Australia | 108 | IR/HR PCa for staging | 8.6 (0.18–120) | 20% upstaged, 1% downstaged |
Sachpekidis et al. 2016 [60] | P | Heidelberg, Germany | 24 | HR PCa | 24.1 (3.2–200) | N/A |
Schwenck et al. 2016 [61] | P | Tübingen, Germany | 20 | HR PCa for staging, PSMA vs choline | 26 (N/A) | N/A |
Sterzing et al. 2016 [62] | R | Heidelberg, Germany | 15 | HR PCa for staging | 7 (0.28–45) | 13.7% changed their TNM staging |
Uprimny et al. 2017 [63] | R | Innsbruck, Austria | 90 | PCa, other analysis | 9.7 (2.2–188.4) | N/A |
Van Leeuwen et al. 2017 [64] | P | Sydney, Australia | 30 | IR/HR PCa prior to RP | 8.1 (5.2–10.1) | Se 58%, spec 100%, PPV 94%, NPV 98% |
Zamboglou et al. 2015 [65] | R | Freiburg, Germany | 22 | PCa prior to RT planning | 20.4 (1.22–66.9) | GTV-PET larger than GTV-MRI |
Author and year | N | Inclusion criteria | Median PSA level, ng/mL (range) | Change in planned pelvic RT | ||
---|---|---|---|---|---|---|
% local plan change | % extra-pelvic disease | local plan change details | ||||
Calais et al. 2018 [54] | 73 | IR/HR PCa prior to RT planning | 13.9 (0.22–909) | 7–19.5%a | 9.5% | covered pelvic LNs detected |
Frenzel et al. 2018 [51] | 20 | PCa prior to RT planning | 7.1 (0.48–137) | 15% | N/A | shifted from IR to HR, one patient had boost to distant PET findings |
Hruby et al. 2018 [55] | 109 | IR/HR PCa prior to RT planning | 9.9 (1.23–240) | 14.7% | 6.4% | covered pelvic LNs detected |
Roach et al. 2017 [44] | 108 | IR/HR PCa prior to RP/ EBRT/ systemic treatment | 8.6 (0.18–120) | 15% | 9% | higher dose and volume |
Sterzing et al. 2016 [62] | 15 | HR PCa for staging | 7 (0.28–45) | 13% | N/A | covered pelvic LNs detected |
Treatment outcomes of dRT for PCa
Current prospective trials evaluating the impact of PSMA PET/CT on prostate RT planning
Rationale for study design and hypothesis
Objective of the trial
Trial design
Methods
Study population
Intervention
Study procedure
Investigational PET imaging drug
PET/CT imaging protocol specifics
PET/CT imaging analysis and image transfer
Radiation therapy (RT) management
Outcome measures
Primary Endpoint Measures
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A biochemical recurrence defined as a rise by 2 ng/mL or more above the nadir PSA (defined as the lowest PSA achieved) after radiotherapy with or without short-term hormonal therapy [67].
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Appearance of metastasis or loco-regional recurrence (diagnosed by any imaging or biopsy).
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Initiation of any new salvage therapy
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Death from any cause.
Secondary endpoints measures
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Diagnosis of local recurrence or pelvic nodal disease (N1) can be obtained by any imaging or biopsy.
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Death from any cause
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Diagnosis of extra-pelvic metastatic (M1) disease can be obtained by any imaging or biopsy.
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Death from any cause
Timeline
Screening and enrollment
Randomization and intervention
Outcome follow-up
Study duration
Sample size determination
Allocation sequence generation, concealment mechanism and implementation
Data collection, management and monitoring
Statistical methods
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Per-Protocol Analysis Dataset: n = 300 (sample size in each group is n = 150)
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Intention-to-Treat (ITT) Analysis Dataset: n = 312 (all randomized participants)
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Safety Analysis Dataset: n = 162 (intervention arm 2, PSMA PET/CT scan)