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International Journal of Urology (2015) 22, 82–87
doi: 10.1111/iju.12604
Original Article: Clinical Investigation
Significance of early prostate-specific antigen values after salvage radiotherapy in recurrent prostate cancer patients treated with surgery Ji Hyun Chang,1 Won Park,2 Jun Su Park,2 Hongryull Pyo,2 Seung Jae Huh,2 Han Yong Choi,3 Hyun Moo Lee,3 Seong Soo Jeon3 and Seong Il Seo3 1
Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, and Departments of 2Radiation Oncology and 3Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Abbreviations & Acronyms ADT = androgen deprivation therapy BCF = biochemical failure BCFFS = biochemical failure-free survival CRFS = clinical recurrence-free survival iPSA = initial prostate specific antigen OS = overall survival PCSS = prostate cancer-specific survival PSA = prostate-specific antigen PSApostSRT4mo ≥ 0.2 = prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months RP = radical prostatectomy RT = radiotherapy SRT = salvage radiotherapy Correspondence: Won Park M.D., Ph.D., Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea. Email: [email protected] Received 10 April 2014; accepted 23 July 2014. Online publication 10 September 2014
82
Objectives: To assess the use of post-salvage radiotherapy prostate-specific antigen for early prediction of biochemical failure or clinical recurrence after salvage radiotherapy in recurrent prostate cancer patients after prostatectomy. Methods: From 2000 to 2011, 164 patients were treated with salvage radiotherapy alone for recurrent prostate cancer. Patients who received androgen deprivation therapy before or within 1 month of the termination of salvage radiotherapy were excluded. Survival analysis was carried out with: (i) a selected prostate-specific antigen reference value (0.2 ng/mL) at the second follow-up period (4 months) after salvage radiotherapy (prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months); and (ii) prostate-specific antigen percent decline (post-salvage radiotherapy 4 months prostate-specific antigen/presalvage radiotherapy prostate-specific antigen). Results: The median follow-up time was 53.4 months (range 8.5–134.1 months). The 5-year clinical recurrence-free survival was 87.9%. Prostate-specific antigen percent decline of 0.45 was set as the cut-off value for clinical recurrence-free survival based on the receiver operating characteristics curve. In the multivariate analysis, a prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months (P = 0.013) and prostate-specific antigen percent decline ≥ 0.45 (P = 0.002) were both significant parameters predicting clinical recurrence-free survival. Otherwise, prostate-specific antigen percent decline ≥ 0.45 was the only statistically significant predictor of biochemical failure-free survival (biochemical failurefree survival after salvage radiotherapy). Conclusions: A prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months and prostate-specific antigen percent decline ≥ 0.45 are negative predictors of clinical recurrence-free survival after salvage radiotherapy. Prostate-specific antigen percent decline ≥ 0.45 is also associated with worse biochemical failure-free survival after salvage radiotherapy. Patients with delayed prostate-specific antigen decrease should be carefully observed for clinical recurrence.
Key words: prostate cancer, prostate specific antigen, radiotherapy, recurrence, salvage.
Introduction The importance of SRT is continuously growing as a result of a high recurrence rate of 25–30% after RP.1,2 However, debate continues over the use of SRT for recurrent prostate cancer after RP. Features of SRT compared with adjuvant RT including the time of SRT initiation, SRT dose, combination of ADT, and pelvic lymph node region RT remain issues of concern. Additionally, no consensus has been reached on the definition of PSA failure after SRT and the starting time of third-line treatment. The unique feature of salvage treatment in prostate cancer is that it can be given only with PSA elevation after prostatectomy, regardless of radiological or pathological evidence of recurrence. This is not only because PSA is a surrogate marker of recurrence, but also due to the difficulty of imaging or pathological confirmation.1 Numerous studies reported BCF for the end-point after SRT.3–9 However, the significance of BCF after SRT is less of an issue compared with postoperative adjuvant RT, as the presence of only BCF after SRT alone is not a critical factor for initiating third-line salvage treatment, such as ADT or chemotherapy. This is mainly because not all BCF patients eventually present as clinical failure. © 2014 The Japanese Urological Association
Early PSA after SRT in prostate cancer
Reported BCF outcome after SRT varies among studies, partly as a result of the diverse criteria defining BCF.3–8 Furthermore, in many of the patients from these studies, ADT is carried out and interferes with the interpretation of BCFFS (BCFFS after SRT). In practice, ADT is often administered to relatively high-risk patients that are assumed to have worse survival outcome, and might mask PSA recurrence; therefore, its contribution to increased survival is questionable.1 Furthermore, ADT before RT has been reported to be related to lower PCSS.10 In assessing the outcome of SRT, most of the reports document that pre-SRT factors, such as postoperative PSA velocity, pre-SRT PSA levels, PSA doubling time or interval to relapse, predict the outcomes.3,6,8 However, after SRT, post-SRT PSA values or kinetics are often overlooked when making further clinical decisions. Little research has been carried out to evaluate post-SRT parameters associated with PSA for survival analysis. In the present study, we retrospectively analyzed whether early post-PSA parameters after SRT in recurrent prostate cancer patients treated with surgery were related to clinical outcome and prediction of BCFFS after SRT or post-SRT clinical failure. In particular, we focused on the early PSA parameters after SRT to investigate whether early response to SRT can predict further survival outcome.
Methods Patients Of 1728 patients who underwent RP for prostate cancer, all data from 215 (12.4%) patients who received SRT after RP from November 2000 to November 2011 were retrieved from the archives of a single institution. All patients were confirmed for adenocarcinoma of the prostate and underwent RP. During the follow up after RP, SRT was considered when two consecutive rises of PSA occurred after surgery. Patients with node-positive disease (n = 4), who received RT to the whole pelvis (n = 3) and who received SRT with ADT (n = 44) were excluded. Consequently, 164 patients were included in the present study. Medical records including PSA values, imaging scans, and clinical and pathological findings were investigated. The median patient age was 66 years (range 42–84 years). Detailed information on the patient characteristics is presented in Table 1. The median pre-SRT PSA nadir was 0.41 ng/mL (range 0.05–5.78 ng/mL). The median time from RP to initiation of SRT was 22 months (range 4–121 months), and the pre-SRT PSA evaluation was carried out within 1 month before the initiation of SRT.
Treatment Before November 2008, all patients received 3-D conformal RT, and intensity-modulated radiation therapy was applied after November 2008. SRT was delivered to the prostate fossa including the retrovesical region, which is considered as the preoperative tumor bed. The median SRT dose was 70 Gy (range 60–78 Gy). Dose-fractionation schemes varied according to the need for dose escalation and hypofractionation from recent reports.11,12 Of the 164 patients, 143 (87%) received a total RT dose of 60–78 Gy with 2 Gy per fraction, using 3-D conformal RT with 10–15 MV photons. The other 21 patients underwent intensity-modulated radiation therapy with a total © 2014 The Japanese Urological Association
Table 1
Patient characteristics
Characteristics Age (years) Median (range) iPSA (ng/mL) Median (range) Pathological Gleason score
International Journal of Urology (2015) 22, 82–87
doi: 10.1111/iju.12604
Original Article: Clinical Investigation
Significance of early prostate-specific antigen values after salvage radiotherapy in recurrent prostate cancer patients treated with surgery Ji Hyun Chang,1 Won Park,2 Jun Su Park,2 Hongryull Pyo,2 Seung Jae Huh,2 Han Yong Choi,3 Hyun Moo Lee,3 Seong Soo Jeon3 and Seong Il Seo3 1
Department of Radiation Oncology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, and Departments of 2Radiation Oncology and 3Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Abbreviations & Acronyms ADT = androgen deprivation therapy BCF = biochemical failure BCFFS = biochemical failure-free survival CRFS = clinical recurrence-free survival iPSA = initial prostate specific antigen OS = overall survival PCSS = prostate cancer-specific survival PSA = prostate-specific antigen PSApostSRT4mo ≥ 0.2 = prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months RP = radical prostatectomy RT = radiotherapy SRT = salvage radiotherapy Correspondence: Won Park M.D., Ph.D., Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea. Email: [email protected] Received 10 April 2014; accepted 23 July 2014. Online publication 10 September 2014
82
Objectives: To assess the use of post-salvage radiotherapy prostate-specific antigen for early prediction of biochemical failure or clinical recurrence after salvage radiotherapy in recurrent prostate cancer patients after prostatectomy. Methods: From 2000 to 2011, 164 patients were treated with salvage radiotherapy alone for recurrent prostate cancer. Patients who received androgen deprivation therapy before or within 1 month of the termination of salvage radiotherapy were excluded. Survival analysis was carried out with: (i) a selected prostate-specific antigen reference value (0.2 ng/mL) at the second follow-up period (4 months) after salvage radiotherapy (prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months); and (ii) prostate-specific antigen percent decline (post-salvage radiotherapy 4 months prostate-specific antigen/presalvage radiotherapy prostate-specific antigen). Results: The median follow-up time was 53.4 months (range 8.5–134.1 months). The 5-year clinical recurrence-free survival was 87.9%. Prostate-specific antigen percent decline of 0.45 was set as the cut-off value for clinical recurrence-free survival based on the receiver operating characteristics curve. In the multivariate analysis, a prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months (P = 0.013) and prostate-specific antigen percent decline ≥ 0.45 (P = 0.002) were both significant parameters predicting clinical recurrence-free survival. Otherwise, prostate-specific antigen percent decline ≥ 0.45 was the only statistically significant predictor of biochemical failure-free survival (biochemical failurefree survival after salvage radiotherapy). Conclusions: A prostate-specific antigen value over 0.2 ng/mL at post-salvage radiotherapy 4 months and prostate-specific antigen percent decline ≥ 0.45 are negative predictors of clinical recurrence-free survival after salvage radiotherapy. Prostate-specific antigen percent decline ≥ 0.45 is also associated with worse biochemical failure-free survival after salvage radiotherapy. Patients with delayed prostate-specific antigen decrease should be carefully observed for clinical recurrence.
Key words: prostate cancer, prostate specific antigen, radiotherapy, recurrence, salvage.
Introduction The importance of SRT is continuously growing as a result of a high recurrence rate of 25–30% after RP.1,2 However, debate continues over the use of SRT for recurrent prostate cancer after RP. Features of SRT compared with adjuvant RT including the time of SRT initiation, SRT dose, combination of ADT, and pelvic lymph node region RT remain issues of concern. Additionally, no consensus has been reached on the definition of PSA failure after SRT and the starting time of third-line treatment. The unique feature of salvage treatment in prostate cancer is that it can be given only with PSA elevation after prostatectomy, regardless of radiological or pathological evidence of recurrence. This is not only because PSA is a surrogate marker of recurrence, but also due to the difficulty of imaging or pathological confirmation.1 Numerous studies reported BCF for the end-point after SRT.3–9 However, the significance of BCF after SRT is less of an issue compared with postoperative adjuvant RT, as the presence of only BCF after SRT alone is not a critical factor for initiating third-line salvage treatment, such as ADT or chemotherapy. This is mainly because not all BCF patients eventually present as clinical failure. © 2014 The Japanese Urological Association
Early PSA after SRT in prostate cancer
Reported BCF outcome after SRT varies among studies, partly as a result of the diverse criteria defining BCF.3–8 Furthermore, in many of the patients from these studies, ADT is carried out and interferes with the interpretation of BCFFS (BCFFS after SRT). In practice, ADT is often administered to relatively high-risk patients that are assumed to have worse survival outcome, and might mask PSA recurrence; therefore, its contribution to increased survival is questionable.1 Furthermore, ADT before RT has been reported to be related to lower PCSS.10 In assessing the outcome of SRT, most of the reports document that pre-SRT factors, such as postoperative PSA velocity, pre-SRT PSA levels, PSA doubling time or interval to relapse, predict the outcomes.3,6,8 However, after SRT, post-SRT PSA values or kinetics are often overlooked when making further clinical decisions. Little research has been carried out to evaluate post-SRT parameters associated with PSA for survival analysis. In the present study, we retrospectively analyzed whether early post-PSA parameters after SRT in recurrent prostate cancer patients treated with surgery were related to clinical outcome and prediction of BCFFS after SRT or post-SRT clinical failure. In particular, we focused on the early PSA parameters after SRT to investigate whether early response to SRT can predict further survival outcome.
Methods Patients Of 1728 patients who underwent RP for prostate cancer, all data from 215 (12.4%) patients who received SRT after RP from November 2000 to November 2011 were retrieved from the archives of a single institution. All patients were confirmed for adenocarcinoma of the prostate and underwent RP. During the follow up after RP, SRT was considered when two consecutive rises of PSA occurred after surgery. Patients with node-positive disease (n = 4), who received RT to the whole pelvis (n = 3) and who received SRT with ADT (n = 44) were excluded. Consequently, 164 patients were included in the present study. Medical records including PSA values, imaging scans, and clinical and pathological findings were investigated. The median patient age was 66 years (range 42–84 years). Detailed information on the patient characteristics is presented in Table 1. The median pre-SRT PSA nadir was 0.41 ng/mL (range 0.05–5.78 ng/mL). The median time from RP to initiation of SRT was 22 months (range 4–121 months), and the pre-SRT PSA evaluation was carried out within 1 month before the initiation of SRT.
Treatment Before November 2008, all patients received 3-D conformal RT, and intensity-modulated radiation therapy was applied after November 2008. SRT was delivered to the prostate fossa including the retrovesical region, which is considered as the preoperative tumor bed. The median SRT dose was 70 Gy (range 60–78 Gy). Dose-fractionation schemes varied according to the need for dose escalation and hypofractionation from recent reports.11,12 Of the 164 patients, 143 (87%) received a total RT dose of 60–78 Gy with 2 Gy per fraction, using 3-D conformal RT with 10–15 MV photons. The other 21 patients underwent intensity-modulated radiation therapy with a total © 2014 The Japanese Urological Association
Table 1
Patient characteristics
Characteristics Age (years) Median (range) iPSA (ng/mL) Median (range) Pathological Gleason score
