The key role of PSA doubling time in patients treated with salvage radiation therapy after radical prostatectomy: Implications for the extent of radiation and the concomitant use of hormonal therapy

PURPOSE: To identify factors predictive of local recurrence as defined by a complete response to salvage radiation therapy in patients whose disease recurs after radical prostatectomy. PATIENTS AND METHODS: Ninety-five patients with recurrence after radical prostatectomy who were evaluated by prostatic fossa biopsies, and a subset of 49 of these patients treated with radiation for control of presumed or biopsy-proven local recurrence, were studied. RESULTS: Biopsies were positive in 40 (42%) of the 95 biopsied patients. Multivariate analysis revealed that prebiopsy prostate-specific antigen (PSA) level, postrecurrence PSA doubling time, and positive digital rectal examination (DRE) of the prostatic fossa were all statistically significant predictors of a positive biopsy. For the 49 patients subsequently treated with salvage radiation therapy, the overall actuarial 3- and 5-year PSA relapse-free probabilities were 43% and 24%, respectively. Univariate analysis showed no differences in the PSA relapse-free probabilities associated with any pathologic features of the radical prostatectomy specimen, biopsy confirmation of local recurrence, or DRE of the prostatic fossa. In multivariate analysis, controlling for all other variables, preradiation PSA and postrecurrence PSA doubling time measured before radiation were the only statistically significant predictors of outcome. CONCLUSION: DRE of the prostatic fossa, prebiopsy PSA, and postrecurrence PSA doubling time predict which patients will have biopsy-proven local recurrence. However, response to salvage radiation therapy is associated with postrecurrence PSA doubling time and with preradiation PSA level only. DRE of the prostatic fossa and biopsy confirmation of local recurrence are not associated with salvage radiation outcome.

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Predicting the Outcome of Salvage Radiation Therapy for Recurrent Prostate Cancer After Radical Prostatectomy

Journal of Clinical Oncology ◽

10.1200/jco.2006.08.9607 ◽

2007 ◽

Vol 25 (15) ◽

pp. 2035-2041 ◽

Cited By ~ 607

Author(s):

Andrew J. Stephenson ◽

Peter T. Scardino ◽

Michael W. Kattan ◽

Thomas M. Pisansky ◽

Kevin M. Slawin ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Radical Prostatectomy ◽

Doubling Time ◽

Medical Decision ◽

Gleason Grade ◽

Recurrent Prostate Cancer ◽

Cox Regression Analysis ◽

Salvage Radiation Therapy ◽

Psa Doubling Time

Purpose An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence. Patients and Methods Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients. Results The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69. Conclusion Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.

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1501 ESTABLISHING A THRESHOLD FOR PSA DOUBLING TIME IN PREDICTING OUTCOMES FOLLOWING SALVAGE RADIATION THERAPY

The Journal of Urology ◽

10.1016/j.juro.2013.02.2980 ◽

2013 ◽

Vol 189 (4S) ◽

Author(s):

Todd Morgan ◽

William C. Jackson ◽

Skyler Johnson ◽

David C. Miller ◽

Jeffrey S. Montgomery ◽

...

Keyword(s):

Radiation Therapy ◽

Doubling Time ◽

Salvage Radiation Therapy ◽

Psa Doubling Time

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Redefining the role of adjuvant versus salvage radiation therapy for prostate cancer after radical prostatectomy for T3 disease and/or positive margins.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.367 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 367-367

Author(s):

Barry W. Goy ◽

In-Lu Amy Liu

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

High Risk ◽

Radical Prostatectomy ◽

Hormonal Therapy ◽

Salvage Therapy ◽

Low Risk ◽

Adjuvant Radiation ◽

Positive Margins ◽

Salvage Radiation Therapy

367 Background: SWOG 8794 recommends adjuvant radiation therapy (ART) after radical prostatectomy (RP) for T3 and/or positive margins. Our purpose was to assess 12-year outcomes on 862 RP patients who had either T3 and/or positive margins who underwent surveillance, salvage radiation therapy (SRT), or hormonal therapy (HT), while categorizing these patients into very low risk (VLR), low risk (LR), high risk (HR), and ultra high risk (UHR) groups. Methods: From 2004 - 2007, 862 RP patients had adverse factors of extracapsular penetration (T3a), seminal vesicle invasion (T3b), positive margins, and/or detectable post-operative PSA. Management included surveillance (54.8%), SRT (36.8%), and HT (8.5%) as first salvage therapy, and 21.5% eventually received hormonal therapy. Twenty patients underwent ART, and were excluded from this analysis. We assessed prognostic factors using multivariable analysis, and 12-year estimates of freedom from biochemical failure (FFBF), freedom from salvage therapy (FFST), distant metastases-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS). VLR were those with Gleason Score (GS) of 6. LR were GS 3+4 with only T3a or positive margins, but an undetectable postoperative PSA <0.1. HR were T3b with GS 7-10, any GS 7-10 with T3a/b and positive margins, but an undetectable PSA. UHR were those with a detectable PSA with a GS 7-10. Results: Median follow-up was 12.1 years. Median age was 61.6 years. Median time to first salvage treatment for VLR, LR, HR, and UHR were 10.8, 11.1, 5.3, and 0.6 years, p<0.001. 12-year estimates of FFBF for VLR, LR, HR, and UHR were 60.2%, 52.9%, 28.4%, and 0%, p<0.0001. For FFST, 70.9%, 68.6%, 40.5%, and 0%, p<0.0001. For DMFS, 99.1%, 97.8%, 88.6%, and 63.6%, p<0.0001. For PCSS, 99.4%, 99.5%, 93.5%, and 78.9%, p<0.0001. For OS, 91.8%, 91.8%, 81.0%, and 69.9%, p<0.0001. Conclusions: Outcomes of T3 and/or positive margins using surveillance or SRT as initial management yields excellent outcomes for VLR and LR groups, in which ART should be avoided. For HR, ART can be considered reasonable, since FFBF is only 28.4%. For VHR, these patients may benefit from combined hormonal therapy and ART.

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PSA doubling time of ≤6 months as the optimal cutoff for predicting clinically relevant outcomes for men receiving salvage radiation therapy post radical prostatectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.167 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 167-167

Author(s):

William C. Jackson ◽

Skyler B. Johnson ◽

Benjamin Foster ◽

Corey Foster ◽

Yeohan Song ◽

...

Keyword(s):

Radiation Therapy ◽

Radical Prostatectomy ◽

Predictive Value ◽

Doubling Time ◽

Univariate Analysis ◽

External Beam Radiation ◽

Beam Radiation ◽

Data Set ◽

Psa Doubling Time ◽

The Impact

167 Background: Short PSA doubling time (PSADT) after biochemical recurrence (BR) post radical prostatectomy (RP) is known to predict worse outcomes following salvage external beam radiation therapy (SRT). The ideal PSADT cut-off, however, in this context remains uncertain. In this study, we sought to identify the best PSADT cut-off for predicting clinical outcomes following SRT for BR after RP. Methods: 575 patients who received SRT at a single institution for BR after RP were retrospectively reviewed in an IRB approved analysis. The impact of PSADT on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) was assessed using Kaplan-Meier and Cox Proportional Hazards models. Results: Median follow up was 56.7 months post SRT. PSADTs could be calculated for 277 patients. PSADT strongly predicted BF, DM, PCSM, and OS on univariate analysis regardless of cut-off point. There was no statistical difference in BF, DM, PCSM, or OS between patients with PSADT <3 (n=40) and 3-6 months (n=61) or between 6-10 (n=62) and >10 months (n=114). A difference existed in BF (p<0.01 HR: 2.2 [95%CI: 1.4-3.5]) and DM (p=0.02 HR: 2.2 [95%CI: 1.2-4.3]) between PSADT of 3-6 and 6-10 months. PSADT ≤6 had the largest positive predictive value (PPV) for BF (70%), DM (36%), and PCSM (13%) at 5 years. There was no difference in negative predictive value between a PSADT >10 vs. >6 months for BF, DM, PCSM, and OS with 5 year rates of (60% vs. 60%, 86% vs. 86%, 99% vs. 98%, and 95 vs. 94% respectively). On multivariate analysis PSADT ≤6 was a strong predictor of BF (p<0.01 HR: 2.1 [95%CI: 1.5-3.0]), DM (p=0.01 HR: 2.0 [95%CI: 1.2-3.4]), and PCSM (p=0.04 HR: 2.3 [95%CI: 1.1-5.2]), with a trend towards predicting OS (p=0.12 HR: 1.5 [95%CI: 0.9-2.6]). Conclusions: A PSADT ≤6 months was the best predictor of outcomes in our data set, particularly for DM and PCSM. Currently, the most common predictive nomogram for SRT uses PSADT <10 months as the cut-off point for BF. These results suggest that using a PSADT of ≤6 months may improve the ability to predict clinically significant outcomes and hence identify men who may benefit from additional therapy.

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