Efficacy and toxicity of conventionally fractionated pelvic radiation with a hypofractionated simultaneous versus conventionally fractionated sequential boost for patients with high-risk prostate cancer

Figures & data

Table I. Pretreatment characteristics.

	Conventionally Fractionated (n = 82)	Hypofractionated (n = 75)	p-value
Age at RT start; mean (range)	66.9 (46–83)	67.9 (48–83)	0.733*
PSA (ng/mL); mean (range)	25.9 (1.1–187)	23.89 (0.0–60.5)	0.195**
Gleason score:
≤ 6	20 (24%)	7 (9%)	0.013*
= 7	13 (16%)	19 (25%)	0.141^†
≥ 8	49 (60%)	49 (65%)	0.519^†
PSA > 20 ng/mL	40 (49%)	29 (39%)	0.202^†
T3	8 (10%)	6 (8%)	0.700^†
T3 determined by:
Physical exam	3 (4%)	4 (5%)	0.838^†
MRI	3 (4%)	2 (3%)	0.908^†
Transrectal ultrasound	1 (1%)	0	0.623^†
CT	1 (1%)	0	0.623^†
Two or more high-risk features	19 (23%)	15 (20%)	0.630^†
Neoadjuvant ADT	76 (93%)	68 (91%)	0.647^†

*Independent samples t-test, **Independent samples Kruskal-Wallis test, ^†Pearson χ².

ADT, androgen deprivation therapy; RT, radiotherapy; PSA, prostate specific antigen.

Except for age and PSA, the values shown represent numbers of patients with percentages in parenthesis.

Figure 1. Biochemical freedom from progression by treatment regimen.

Figure 2. Late rectal toxicity by treatment regimen.

Table II. Description of late toxicity events.

			Conventionally Fractionated (n = 82)	Hypofractionated (n = 75)
Grade 2 GI events	Diarrhea	With endoscopic evidence of proctitis*	2 (2%)	0
		Endoscopy not performed	3 (4%)	0
	Rectal bleeding	With endoscopic evidence of proctitis*	4 (5%)	1 (1%)
		Endoscopy not performed	8 (10%)	5 (7%)
	Rectal pain		1 (1%)	1 (1%)
		Total	18 (22%)	7 (9%)
Grade 3 GI events	Rectal bleeding	Endoscopic procedure	1 (1%)	1 (1%)
		Blood transfusion	2 (3%)	0
		Total	3 (4%)	1 (1%)
Grade ≥ 3 urinary events	Urethral stricture	Requiring dilatation	2 (2%)	0
		Requiring surgical urethrotomy	0	1 (1%)
	Transient hematuria		2 (2%)	2 (3%)
		Total	4 (5%)	3 (4%)

*Diagnostic endoscopy only.

Table III. Summary of selected publications.

	Study	Design	No. of patients	Disease risk factors	Dose (Prostate/Pelvis)	Fraction size	ADT timing	Early toxicity (GI/GU)	Late GI toxicity	Late GU toxicity	Progression free survival
Conventional Fractionation	RTOG 9413 [5,11]	Phase III	639	LN Risk > 15%	70.2/50.4 Gy	1.8 Gy	Neoadjuvant and adjuvant	2%/3% grade ≥ 3	5% grade ≥ 3*		59.6% at 4 years**
	GETUG-01 [12]	Phase III	225	T3, GS ≥ 7, or PSA > 12 ng/mL	66–70/46– 46.8 Gy	1.8–2.25 Gy	Neoadjuvant	32.6%/26.3% grade ≥ 2	31.7% grade ≥ 2	37.7% grade ≥ 2	59.8% at 5 years
	Aizer, et al. [15]	Retrospective	68	LN Risk > 15%	75.6/45 Gy	1.8 Gy	Neoadjuvant	19.1%/41.1% grade ≥ 2	5.9% grade ≥ 2	1.5% grade ≥ 2	86.3% at 5 years
	McDonald et al. (current)	Retrospective	82	NCCN High-Risk	75–77/45 Gy	1.8 Gy to pelvic field, 2.0 Gy boost field	Neoadjuvant	35%/49% grade ≥ 2	25% grade ≥ 2	3% grade ≥ 3	88% at 4 years
Hypofractionation	Adkison et al. [6]	Phase I	53	NCCN High-Risk	70/56 Gy	2.5 Gy prostate, 2.0 Gy pelvis	Neoadjuvant	32%/37% grade = 2	8% grade ≥ 2	2% grade ≥ 2	81.2% at 3 years
	Quon et al. [7]	Phase I/II	97	NCCN High-Risk	67.5/45 Gy	2.7 Gy prostate, 1.8 Gy pelvis	Neoadjuvant and adjuvant	36.3%/43% grade ≥ 2	7% grade ≥ 2	13% grade ≥ 2	90.5% at 4 years
	McCammon et al. [18,19]	Retrospective	30	LN Risk > 15%	70/50.4 Gy	2.5 Gy prostate, 1.8 Gy pelvis	Neoadjuvant	21 events***/ 23.3% grade ≥ 2	5 events ***	13.3% grade ≥ 2	73% at 3.8 years
	McDonald et al. (current)	Retrospective	75	NCCN High-Risk	70/50.4 Gy	2.5 Gy prostate, 1.8 Gy pelvis	Neoadjuvant	36%/44% grade ≥ 2	13% grade ≥ 2	6% grade ≥ 3	94% at 4 years

*Represents only patients treated with neoadjuvant ADT.

**Utilizing protocol definition of biochemical failure rather than nadir + 2 definition.

***Multiple events in same patient possible.

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Aizer A, Yu J, McKeon A, Decker R, Colberg J, Peschel R. Whole pelvic radiotherapy versus prostate only radiotherapy in the management of locally advanced or aggressive prostate adenocarcinoma. Int J Rad Oncol Biol Phys 2009;75: 1344–9.

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Adkison J, McHaffie D, Bentzen S, Patel R, Khuntia D, Petereit D, et al. Phase I trial of pelvic nodal dose escalation with hypofractionated IMRT for high-risk prostate cancer. Int J Rad Oncol Biol Phys 2012;82:184–90.

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Quon H, Cheung P, Loblaw D, Morton G, Pang G, Szumacher E, et al. Hypofractionated concominant intensity-modulated radiotherapy boost for high-risk prostate cancer: Late toxicity. Int J Rad Oncol Biol Phys 2012; 82:898–905.

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McCammon R, Rusthoven K, Kavanagh B, Newell S, Newman F, Raben D. Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer. Int J Rad Oncol Biol Phys 2009;75: 413–20.

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Reddy K, Nelson B, McCammon, Newell S, Newman F, Raben D. Preliminary outcomes for the treatment of intermediate- and high-risk prostate cancer patients using pelvic intensity modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate. Int J Rad Oncol Biol Phys 2010;78:S376.

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