Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy.
BACKGROUND
Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear.


OBJECTIVE
To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics.


METHODS
The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤ 0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥ 0.2 ng/ml.


METHODS
Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤ 6, 7, or ≥ 8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥ 8, and negative surgical margins.


CONCLUSIONS
Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p < 0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors.


CONCLUSIONS
In this retrospective study, cancer control after eSRT greatly depended on pretreatment PSA. The absolute PSA level had a different prognostic value depending on the pathologic characteristics of the tumour. In patients with more adverse pathologic features, eSRT conferred better cancer control when administered at the very first sign of PSA rise. Conversely, the benefit of eSRT was less evident in men with favourable disease at RP.


RESULTS
In this retrospective study, cancer control after early salvage radiation therapy (eSRT) was influenced by pretreatment prostate-specific antigen (PSA) level. This effect was highest in men with at least two of the following pathologic features: pT3b/pT4 disease, pathologic Gleason score ≥ 8, and negative surgical margins. In these patients, eSRT conferred better cancer control when administered at the very first sign of PSA rise.
Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: nicola.fossati@gmail.com.
Nicola
N
Fossati
Department of Urology, Mayo Clinic, Rochester, MN, USA.
R Jeffrey
RJ
Karnes
Department of Radiotherapy, IRCCS Ospedale San Raffaele, Milan, Italy.
Cesare
C
Cozzarini
Medical Physics, San Raffaele Scientific Institute, Milan, Italy.
Claudio
C
Fiorino
Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
Giorgio
G
Gandaglia
University Hospitals Leuven, Department of Urology, Leuven, Belgium.
Steven
S
Joniau
Department of Urology, Mayo Clinic, Rochester, MN, USA.
Stephen A
SA
Boorjian
Klinik für Radioonkologie, Medizinische Universität Wien, Vienna, Austria.
Gregor
G
Goldner
Department of Radiation Oncology, Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin, Germany.
Wolfgang
W
Hinkelbein
University Hospitals Leuven, Department of Radiation Oncology, Leuven, Belgium.
Karin
K
Haustermans
Department of Urology, Université Catholique de Louvain, Brussels, Belgium.
Bertrand
B
Tombal
Department of Urology, Comprehensive Cancer Centre, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
Shahrokh
S
Shariat
Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada.
Pierre I
PI
Karakiewicz
Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
Francesco
F
Montorsi
University Hospitals Leuven, Department of Urology, Leuven, Belgium.
Hein
H
Van Poppel
Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany.
Thomas
T
Wiegel
Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
Alberto
A
Briganti
D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D000368:Aged; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000009:adverse effects*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D015854:Up-Regulation
C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
Biochemical tumour markers; Neoplasm recurrence; Prostatic neoplasms; Radiotherapy; Salvage therapy