Rationale and development of image-guided intensity-modulated radiotherapy post-prostatectomy: the present standard of care?

Figures & data

Table 1 Summary of the four consensus guidelines and guidance from the RADICALS trial for post-prostatectomy target delineation

Guideline	Inferior	Superior	Lateral	Anterior	Posterior	CTV^Citation49 (cm^3), mean ± SD	PTV^Citation49 (cm^3), mean ± SD
Princess Margaret Hospital Wiltshire et al^Citation39	8 mm below the VUA or the top of the PB, whichever is most superior	Superior surgical clips if present, or 5 mm above the inferior border of the vas deferens. Retained SV included when pathologically involved	Caudal: medial border of the levator ani and obturator internus. Cranial: Sacrorecto-genitopubic fascia	Caudal: posterior edge of the symphysis pubis up to the top of the symphysis pubis Cranial: posterior 1.5 cm of the bladder wall	Caudal: anterior border of the rectal wall and levator ani Cranial: mesorectal fascia	104±25	350±50
Australian and New Zealand Radiation Oncology Genito-Urology Group Sidhom et al^Citation46	5–6 mm below the VUA, but should include all surgical clips inferiorly. If VUA not clearly defined, then slice above the PB	Encompass all of the SV bed as defined by non vascular clips and should include distal portion of the vas deferens. If SV pathologically involved, include any residual SV	Medial border of the levator ani muscle or obturator internus muscle	Lower border of CTV to 3 cm superior, posterior aspect of the symphysis pubis More superiorly: posterior 1.5 cm of the bladder	Levator ani and anterior rectal wall. More superiorly, anterior mesorectal fascia	88±16	325±32
Radiation Therapy Oncology Group Michalski et al^Citation47	8–12 mm below VUA, may include more if concern for apical margin. Can extend to slice above PB if VUA not well visualized	Level of cut end of vas deferens or 3–4 cm above top of symphysis. Include SV remnants if pathologically involved	Below superior edge of symphysis pubis: levator ani muscles, obturator internus Above superior edge of symphysis pubis: Sacrorecto-genitopubic fascia*	Below superior edge of symphysis pubis: posterior edge of pubic bone Above superior edge of symphysis pubis: posterior 1–2 cm of bladder wall	Below superior edge of symphysis pubis: Anterior rectal wall Above superior edge of symphysis pubis: Mesorectal fascia	102±24	351±46
EORTC (^#identified areas of greatest risk of relapse)** Poortmans et al^Citation48	Apex^# −15 mm cranially from the PB +5 mm in all directions***	Bladder neck^# +5 mm in all directions*** Original site of the base of SV should be included. If SV involved, include original position ± the remnants	Up to the neurovascular bundles (if removed up to the ilio-obturatic muscles) +5 mm in all directions***	Anastomosis and urethral axis +5 mm in all directions***	Up to but not including the outer rectal wall, cranially including the most posterior part of the bladder neck +5 mm in all directions***	60±17	254±53
RADICALS guidance 2007 Parker et al^Citation31	5 mm cranial to the superior border of the PB	If SV low risk and pathology uninvolved: base of SV If SV low risk and pathology involved: tips of SV If SV absent, superior border determined with reference to the estimated position of the pre-op SV	Medial border of obturator internus and levator ani muscles	Caudal (less than 2 cm above anastomosis): posterior aspect of symphysis pubis Cranial (more than 2 cm above anastomosis): posterior one third of bladder wall	Anterior rectal wall

Notes:

* If there is concern that extraprostatic disease at base may extend to the obturator internus;

** supplementary 5 mm in the posterior and lateral directions in the presence of incompletely resected extracapsular nodal extension, but excluding the rectal wall; supplementary 5 mm in the direction of microscopically involved tumor margins as reported by the pathologist (except the rectal wall).

*** Except the rectal wall.

Abbreviations: CTV, clinical target volume; EORTC, European Organisation for Research and Treatment of Cancer; PTV, planning target volume; PB, penile bulb; VUA, vesicourethral anastomosis; SV, seminal vesicles; SD, standard deviation.

Table 2 Comparison of acute toxicity for hypofractionated and conventionally fractionated post-prostatectomy radiotherapy

Reference	Patients (n)	Trial design	Total dose/single dose fractionation (EQD2)	Treatment technique	Acute GI toxicity (%)	Acute GU toxicity (%)	Scoring system
Conventionally fractionated post-prostatectomy radiotherapy
De Meerleer et al^Citation27	135	Retrospective	Median 75 Gy/2 Gy	IMRT, regular IGRT	G2: 15	G2: 28	In-house
					G3: 0	G3: 3
Cozzarini et al^Citation67	153	Retrospective	Median 66.6 Gy/1.8 Gy	Conventional non-conformal, 3D-CRT	G2/3: 17.5	G2: 10.5	RTOG
	181		Median		G2/3: 14	G3: 4
			70.2 Gy/1.8 Gy			G2: 11.5
						G3: 2
Nath et al^Citation89	50	Retrospective	Median 68 Gy/1.8–2 Gy	IMRT, daily IGRT	G2: 8	G2: 14	NCI CTCAE
					G3: 0	G3: 0	v. 3.0
Riou et al^Citation90	57	Retrospective	Mean 68 Gy/2 Gy	IMRT, IGRT	G2: 4	G2: 7	NCI CTCAE
					G3: 0	G3: 0	v. 3.0
Bellavita et al^Citation66	182	Retrospective	Median 66.6 Gy/1.8–2 Gy	3D-CRT	G2: 39	G2: 21	RTOG
					G3: 1	G3: 0
Hypofractionated post-prostatectomy radiotherapy
Massaccesi et al^Citation81	49	Prospective, non-randomized Phase II	62.5 Gy/2.5 Gy (71.4 Gy)	SIB-IMRT	G2: 32.6	G2: 9.6	RTOG
					G3: 0	G3: 0
Cozzarini et al^Citation83	50	Prospective, non-randomized Phase I/II	58 Gy/2.9 Gy (72.9 Gy)	Tomotherapy, daily IGRT	G2: 4	G2: 10	RTOG
					G3: 0	G3: 2
Kruser et al^Citation84	108	Retrospective	65 Gy/2.5 Gy (74.3 Gy)	Tomotherapy, daily IGRT, endorectal balloon	G2: 14	G2: 7	Modified
					G3: 0	G3: 1	RTOG
Katayama et al^Citation85	39	Prospective, non-randomized Phase II	54 Gy/3 Gy (69.4 Gy)	Tomotherapy, daily IGRT	G2: 18	G2: 0	NCI CTCAE
					G3: 0	G3: 0	v. 4.0
Gladwish et al^Citation86	30	Prospective, non-randomized Phase I/II	51 Gy/3 Gy (65.6 Gy)	IMRT, daily IGRT (fiducial-based)	G2: 0	G2: 3	NCI CTCAE
					G3: 0	G3: 3	v. 3.0

Note: EQD2, 2 Gy-equivalent dose (assumed α/β ratio of 1.5 Gy).

Abbreviations: GI, gastrointestinal; GU, genitourinary; IGRT, image-guided radiotherapy; IMRT, intensity modulated radiotherapy; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; RTOG, Radiation Therapy Oncology Group; 3D-CRT, three-dimensional conformal radiotherapy; SIB-IMRT, simultaneous integrated boost intensity modulated radiotherapy; G, grade.

Table 3 Interfraction prostate bed motion and calculated margins based on interfraction motion

Reference	Patients/images IGRT method	Interfraction PBM	Lateral mm (SD)	Superior–inferior mm (SD)	Anterior–posterior mm (SD)
Schiffner et al^Citation110	10/163	Mean:	0.3 (0.9)	0.4 (2.4)	−1.1 (2.1)
	Gold seeds, EPID
Sandhu et al^Citation116	26/692	Mean magnitude:	1 (1.7)	2.4 (2.1)	2.7 (2.1)
	Surgical clips, kV
Ost et al^Citation115	15/547	Mean:	0.01	0.58	2.19
	Anterior rectal wall, CBCT	Calculated margin*	1.78	3.27	7.88
Huang et al^Citation103	14/420	Mean:	0	−0.9	1.9
	Surgical clips, CBCT	Calculated margin*	3.24	5.49	8.36
Bell et al^Citation111	40/377	Mean magnitude:
	Surgical clips, CBCT	Upper	0.1 (0.12)	0.28 (0.26)	0.5 (0.5)
		Lower	0.08 (0.1)	0.18 (0.17)	0.18 (0.16)
Alander et al^Citation109	13/466	Mean:	0 (0.5)	0.7 (2.1)	0.8 (1.6)
	Gold seeds, CBCT	Calculated margin**	1.4	5.9	5.9

Notes: PBM, motion of the either the gold seeds, surgical clips, or anterior rectal wall in relation to bony pelvic anatomy and is the mean of the individual patient means, unless otherwise stated. Mean magnitude: average of absolute values of all measurements in a given plane. Margin recipe used:

* 2.5Σ + 0.7σ;

** 1.96Σ + 0.7σ.

Abbreviations: PBM, prostate bed motion; CBCT, cone-beam computed tomography; CTV, clinical target volume; PTV, planning target volume; IGRT, image-guided radiotherapy; SD, standard deviation.

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