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| The role of radiotherapy in localised and locally advanced prostate cancer |
Michel Bollaa,*( ),Ann Henryb,Malcom Masonc,Thomas Wiegeld
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a. Department of Radiation Oncology, Grenoble Alpes University, Grenoble, France;
b. Department of Clinical Oncology, St. James's University Hospital, Leeds, UK;
c.Cardiff University, Velindre Hospital, Whitchurch, UK;
d.Department of Radiation Oncology, University Hospital Ulm, Germany |
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Abstract For a patient suffering from non-metastatic prostate cancer, the individualized recommendation of radiotherapy has to be the fruit of a multidisciplinary approach in the context of a Tumor Board, to be explained carefully to the patient to obtain his informed consent. External beam radiotherapy is now delivered by intensity modulated radiotherapy, considered as the gold standard. From a radiotherapy perspective, low-risk localized prostate cancer is treated by image guided intensity modulated radiotherapy, or brachytherapy if patients meet the required eligibility criteria. Intermediate-risk patients may benefit from intensity modulated radiotherapy combined with 4-6 months of androgen deprivation therapy; intensity modulated radiotherapy alone or combined with brachytherapy can be offered to patients unsuitable for androgen deprivation therapy due to co-morbidities or unwilling to accept it to preserve their sexual health. High-risk prostate cancer, i.e. high-risk localized and locally advanced prostate cancer, requires intensity modulated radiotherapy with long-term (≥2 years) androgen deprivation therapy with luteinizing hormone releasing hormone agonists. Post-operative irradiation, either immediate or early deferred, is proposed to patients classified as pT3pN0, based on surgical margins, prostate-specific antigen values and quality of life. Whatever the techniques and their degree of sophistication, quality assurance plays a major role in the management of radiotherapy, requiring the involvement of physicians, physicists, dosimetrists, radiation technologists and computer scientists. The patients must be informed about the potential morbidity of radiotherapy and androgen deprivation therapy and followed regularly during and after treatment for tertiary prevention and evaluation. A close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life.
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Received: 16 October 2018
Available online: 08 February 2019
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Corresponding Authors:
Michel Bolla
E-mail: MBolla@chu-grenoble.fr
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Dose distributions for intensity-modulated radiotherapy (IMRT) (right) and standard, conformal radiotherapy (left) to the prostate. Note the improved dose distribution and concave high dose volume with IMRT. Courtesy of Dr Gareth Jones, Velindre Hospital, Cardiff.
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| Study/Author | n | Risk, GS, or NCCN | ADT | RT regimen | BED, Gy | Median FU, month | Outcome | | Lee et al. [9] | 550
542 | low risk | None | 70 Gy/28 fx
73.8 Gy/41 fx | 80
69.6 | 70 | 5 year DFS 86.3% (n.s.)
5 year DFS 85.3% | | Dearnaley et al. [10] | 1077/19 fx
1074/20 fx
1065/37 fx | 15% low
73% intermediate
12% high | 3-6 months, before and during EBRT | 57 Gy/19 fx
60 Gy/20 fx
74 Gy/37 fx | 73.3
77.1
74 | 62 | 5 year BCDF
85.9% (19 fx)
90.6% (20 fx)
88.3% (37 fx) | | Aluwini et al. [6] | 403
392 | 30% GS <6, 45% GS >7, 25% GS 8-10 | None | 64.6 Gy/19 fx
78 Gy/39 fx | 90.4
78 | 60 | 5 year RFS 80.5% (n.s.)
5 year RFS 77.1% | | Catton et al. [11] | 608 | intermediate risk
53% T1c
46% T2a-c | None | 60 Gy/20 fx | 77.1 | 72 | 5 year BCDF
both arms 85%
HR: 0.96 (n.s) | | 598 | 9% GS 6
63% GS 7a
28% GS 7b | 78 Gy/39 fx | 78 |
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Major phase III randomised trials of moderate hypofractionation for primary treatment.
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| Comparison of prostate brachytherapy techniques | | LDR | ?
Permanent seeds implanted at single visit
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Uses Iodine-125 (most common), Palladium-103 or Caesium-131 isotopes
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Radiation dose delivered over weeks and months
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Acute side effects resolve over months
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Radiation protection issues for patient and carers
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shielded theatre room
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Established as monotherapy for low and selected intermediate risk localized prostate cancer
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Established as a boost treatment with external beam radiation in higher risk or locally advanced prostate cancer | | HDR | ?
Temporary implantation and may need to be fractionated
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Ir-192 (most common) Co-60 source introduced through implanted applicators (needles or catheters)
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Radiation dose delivered in minutes
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Acute side effects resolve over weeks
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No radiation protection issues for patient or carers
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Can use same HDR source for other cancer treatments
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Need for a shielded HDR treatment room
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Established as boost treatment with external beam radiation in higher risk or locally advanced prostate cancer
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Single centre cohort studies demonstrate good outcomes when used as monotherapy for localised disease |
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Comparison of prostate brachytherapy techniques.
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| Trial | Year | TNM stage | n | Trial | ADT | RT | Effect on OS | | EORTC 22863 [31] | 2010 | T1-2 poorly differentiated
and M0, or T3-4 N0-1 M0 | 415 | EBRT ± ADT | LHRHa for 3 years (adjuvant) | 70 Gy RT | Benefit at 10-year for combined treatment (p = 0.0004) | | RTOG 85-31 [32] | 2005 | T3 or N1 M0 (15% RP) | 977 | EBRT ± ADT | Orchiectomy
or LHRHa | 65-70 Gy RT | Benefit for combined treatment (p = 0.002) mostly caused by patients with Gleason score 7-10 | | D'Amico [7], [8], [9], [10] | 2008 | T2 N0 M0 (localised unfavourable
risk) | 206 | EBRT ± ADT | LHRHa plus flutamide
for 6 mo. | 70 Gy
3D-CRT | Significant benefit (p = 0.01) that may pertain only to men with no or minimal comorbidity | | TROG 96-01 [39] | 2011 | T2b-4 N0 M0 | 802 | Neoadjuvant
ADT duration | LHRHa plus flutamide 3 or 6 mo.
before, plus concomitant | 66 Gy
3D-CRT | Benefit in PCa-specific survival (p = 0.04) | | RTOG 94-13 [40] | 2007 | T1c-4 N0-1 M0 | 1292 | ADT timing comparison | 2 mo. neoadjuvant
plus concomitant
vs. 4 mo.
adjuvant | Whole pelvic RT vs.
prostate only;
70.2 Gy | No significant difference between neoadjuvant plus concomitant vs. adjuvant
androgen suppression
therapy groups (interaction suspected) | | RTOG 86-10 [38] | 2008 | T2-4 N0-1 | 456 | EBRT ± ADT | LHRHa plus flutamide
2 mo. before, plus concomitant | 65-70 Gy RT | No significant difference at 10 year | | RTOG 92-02 [33] | 2008 | T2c-4 N0-1 M0 | 1554 | Short vs. prolonged
ADT | LHRHa given for 2 years as adjuvant after 4 mo. as neoadjuvant | 65-70 Gy RT | 10-year OS benefit in subset with Gleason 8-10 for long-term ADT (p = 0.006) | | EORTC 22961 [34] | 2009 | T1c-2ab N1
M0, T2c-4
N0-1 M0 | 970 | Short vs. prolonged
ADT | LHRHa for 6 mo. vs.
3 years | 70 Gy
3D-CRT | Better 5-year OS with 3-year treatment (p = 0.006) | | SPCG-7/SFUO-3 [35] | 2014 | T1b-2 Grade
2-3, T3 N0 M0 | 875 | ADT ± EBRT | LHRH a for 3 mo plus continuous
flutamide | 70 Gy
3D-CRT vs. no RT | Lower 15-year cancer specific mortality (30.7%) vs. (12.4%) favouring combined treatment (p < 0.0001) | | NCIC CTGMRC/PR3/PRO7/SWOG [36] | 2015 | T3-4 (88%),
PSA >20 ng/mL (64%), GS 8-10 (36%) N0 M0 | 1205 | ADT ± EBRT | Continuous
LHRHa | 65-70 Gy
3D-CRT vs. no RT | 10-year OS benefit for combined treatment (p < 0.001) | | French study [37] | 2012 | T3-4 N0 M0 | 273 | ADT ± EBRT | LHRHa for 3 year | 70 Gy
3D-CRT vs. no RT | Better 5-year progression free survival for combined treatment (p < 0.001) | | 264 |
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