Salvage radiotherapy for biochemical recurrence after radical prostatectomy: does the outcome depend on the prostate cancer characteristics?

Viani, Gustavo Arruda; Hamamura, Ana Carolina; Correa, Alexandre Ciuffi; Arruda, Felipe Teles de

doi:10.1590/S1677-5538.IBJU.2018.0039

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Original Article • IBJUInt. braz j urol 45 (2) • 2019 • https://doi.org/10.1590/S1677-5538.IBJU.2018.0039 copy

Salvage radiotherapy for biochemical recurrence after radical prostatectomy: does the outcome depend on the prostate cancer characteristics?

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To build a model to evaluate the impact of salvage radiotherapy (SRT) in men with PSA rise or persistent PSA after undergoing radical prostatectomy (RP).

Materials and Methods:

The study included 107 node-negative patients treated with SRT after RP at a single institution. Patients received SRT for either prostate-specific antigen (PSA) rising, or PSA persistence after RP. All patients received local radiation to the prostate / seminal vesicle bed. The primary measured outcome was the biochemical recurrence (BCR) free survival. Multivariable Cox regression analysis was used to develop a risk-stratification group to identify predictive factors associated with the probability of BCR at 5yr.

Results:

At a median follow-up of 52 months, the BCR free survival rate and overall survival in 5 years was 73% and 94%, respectively. At multivariable analysis, pre-SRT PSA level > 0.35ng / mL (p = 0.023), negative margins (p = 0.038), and seminal vesicles invasion (p = 0.001) were significantly associated with BCR free survival. Three risk groups using regression analysis for SRT administration was built. Low-, intermediate- and the high-risk groups had a BCR free survival in 5-years of 96%, 84%, and 44% (p = 0.0001), respectively.

Conclusions:

We developed a risk group stratification to show the impact of SRT based on prostate cancer characteristics. SRT showed to be extremely beneficial for patients with low- and intermediate-risk tumors. Moreover, the risk-group built could identify patients classified as high-risk who might benefit from more aggressive treatment for SRT.

Keywords:
Radiotherapy; Prostatectomy; Prostatic Neoplasms

Variables		Median (IQR)
Age at SRT		70 (64 – 75)
Pre operative PSA ng/mL		9 (6 – 13)
Pathological stage
	pT2a-c	41(38.3%)
	pT3a	39(36.4%)
	pT3b	27(25.3%)
Pathological Gleason score
	≤ 6	20 (18.7%)
	7	74 (69.2%)
	8-10	13 (12.1%)
Postoperative PSA persistence
	No	78(72.9%)
	Yes	29(27.1%)
Risk group pre-surgery
	Low	13(10.5%)
	Medium	46(43.8%)
	High	48(45.7%)
Surgical margin status
	Positive	80(74.7%)
	Negative	27(25.3%)
Time between RP and SRT (mo)		14 (7-39)
PSA at SRT (ng/mL)		0.32 (0.23 – 0.52)
RT technique
	3D-RT	71(66.4%)
	IMRT	35(32.7%)
SRT dose (Gy)		70 (66 – 70)
Follow up time after SRT (mo)		52 (36 – 71)
Follow up time after RP (mo)

Variables		% BF control in 5 years	P Value
Age at SRT			0.303
	< 70 years	82%
	≥ 70 years	67%
Gleason			0.125
	≤ 7	90%
	> 7	72%
Extracapsular extention			0.003
	Yes	85%
	No	66%
Seminal vesicles involvement			0.001
	Yes	85%
	No	59%
Postoperative PSA persistence			0.967
	Yes	72%
	No	77%
Risk group pre surgery			0.005
	Low	100
	Medium	80
	High	66
Surgical margin status			0.003
	Positive	88%
	Negative	66%
Time between RP and SRT (mo)			0.623
	< 24 months	72%
	≥ 24 months	77%
PSA at SRT			0.01
	PSA < 0.35	86%
	PSA > 0.35	62%
RT technique			0.393
	3D-RT	74%
	IMRT	76%
SRT dose			0.018
	< 70 Gy	65%
	≥ 70 Gy	79%

Predictor		HR	CI95%	P value
Seminal Vesicles status				0.001
	Negative	1	Ref
	Positive	4.5	1.9-10.7
Surgical margin status				0.038
	Positive	1	Ref
	Negative	2.6	1.06– 6
PSA at SRT				0.023
	PSA < 0.35	1	Ref
	PSA ≥ 0.35	2.76	1.15-6.6

Grade	Acute GU	Acute GI	Late GU	Late GI
0	64 (59.8%)	93 (86.9%)	57 (53.2%)	101 (94.4%)
1	40 (37.4%)	14 (13.1%)	38 (35.5%)	6 (5.6%)
2	3 (2.8%)	0	8 (7.4%)	0
3	0	0	4 (3.7%)	0
4	0	0	0	0

Author	N	PSA at SRT	RT technique	RT dose	Follow-up	BCR	Predictors response
Moreira et al. (¹²12. Moreira DM, Jayachandran J, Presti JC Jr, Aronson WJ, Terris MK, Kane CJ, et al. Validation of a nomogram to predict disease progression following salvage radiotherapy after radical prostatectomy: results from the SEARCH database. BJU Int. 2009;104:1452-6.)	102	0.6 ng/mL	NA	66 Gy	50 mo	6yr:57 %	Surgical margins Pre-SRT PSA levels
Umezawa et al. (¹³13. Umezawa R, Ariga H, Ogawa Y, Jingu K, Matsushita H, Takeda K, et al. Impact of pathological tumor stage for salvage radiotherapy after radical prostatectomy in patients with prostate-specific antigen < 1.0 ng/mL. Radiat Oncol. 2011;6:150.)	102	0.24 ng/mL	NA	64 Gy	44 mo	4yr; 51%	Pathologic stage
Parekh et al. (¹⁴14. Parekh A, Chen MH, Graham P, Mahal BA, Hirsch AE, Nakabayashi M, et al. Role of androgen deprivation therapy in early salvage radiation among patients with prostate-specific antigen level of 0.5 or less. Clin Genitourin Cancer. 2015;13:e1-6.)	108	0.24 ng/mL	NA	66.4 Gy	63 mo	4yr; 45%	Pre-SRT PSA levels ADT
Lohm et al. (¹⁵15. Lohm G, Lütcke J, Jamil B, Höcht S, Neumann K, Hinkelbein W, et al. Salvage radiotherapy in patients with prostate cancer and biochemical relapse after radical prostatectomy : Long-term follow-up of a single-center survey. Strahlenther Onkol. 2014;190:727-31.)	151	0.34 ng/mL	3D-RT	66.6.Gy	82 mo	5yr: 40%	Pre- SRT PSA levels Gleason score PSADT
Present study	107	0.32 ng/mL	3D-RT/IMRT	70 Gy	53 mo	5yr: 73%	Negative margins Pathological stage Pre- SRT PSA levels

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[1] Correspondence address: Gustavo Arruda Viani, MD, Rua Warner Gomes Fernandes, 1045, Marília, SP, 175166-670, Brasil, Fax: +55 14 3402-1744 E-mail: gusviani@gmail.com