Presalvage Prostate-specific Antigen Research Articles

Salvage High-Dose-Rate Brachytherapy for Recurrent Prostate Cancer After Definitive Radiation

PurposeSalvage high-dose-rate brachytherapy (sHDRBT) for locally recurrent prostate cancer after definitive radiation is associated with biochemical control in approximately half of patients at 3 to 5 years. Given potential toxicity, patient selection is critical. We present our institutional experience with sHDRBT and validate a recursive partitioning machines model for biochemical control. Materials and MethodsWe performed a retrospective analysis of 129 patients who underwent whole-gland sHDRBT between 1998 and 2016. We evaluated clinical factors associated with biochemical control as well as toxicity. ResultsAt diagnosis the median prostate-specific antigen (PSA) was 7.77 ng/mL. A majority of patients had T1-2 (73%) and Gleason 6-7 (82%) disease; 71% received external beam radiation therapy (RT) alone, and 22% received permanent prostate implants. The median disease-free interval (DFI) was 56 months, and median presalvage PSA was 4.95 ng/mL. At sHDRBT, 46% had T3 disease and 51% had Gleason 8 to 10 disease.At a median of 68 months after sHDRBT, 3- and 5-year disease-free survival were 85% (95% CI, 79-91) and 71% (95% CI, 62-79), respectively. Median PSA nadir was 0.18 ng/mL, achieved a median of 10 months after sHDRBT. Patients with ≥35%+ cores and a DFI <4.1 years had worse biochemical control (19% vs 50%, P = .02). Local failure (with or without regional/distant failure) was seen in 11% of patients (14/129), and 14 patients (11%) developed acute urinary obstruction requiring Foley placement and 19 patients (15%) developed strictures requiring dilation. ConclusionssHDRBT is a reasonable option for patients with locally recurrent prostate cancer after definitive RT. Those with <35%+ cores or an initial DFI of ≥4.1 years may be more likely to achieve long-term disease control after sHDRBT.

MRI-Guided Ultrafocal Salvage High-Dose-Rate Brachytherapy for Localized Radiorecurrent Prostate Cancer: Updated Results of 50 Patients

Most patients with local prostate cancer recurrence after radiation therapy undergo palliative androgen deprivation therapy because whole-gland salvage treatments have a high risk of severe toxicity. Focal treatment reduces this risk while offering a second opportunity for cure. We report updated outcomes of ultrafocal salvage high-dose-rate brachytherapy (HDR-BT). Prospectively collected data from the first 50 treated patients were analyzed. Disease status was assessed by 3T multiparametric magnetic resonance imaging (MRI), 18F-Choline or 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography, and systematic or tumor-targeted biopsies. Ultrafocal salvage HDR-BT (1 × 19 Gy) was performed by implanting the clinical target volume (CTV: gross tumor volume + 5 mm margin) under fused transrectal ultrasound/MRI guidance. Follow-up included toxicity grading (using Common Terminology Criteria for Adverse Events 4.0), quality of life assessment, and prostate-specific antigen (PSA) testing. Median follow-up was 31 months. Median CTV D95% was 18.8 Gy. We observed 2% grade 3 genitourinary toxicity, no grade 3 gastrointestinal toxicity, and 22% newly developed grade 3 erectile dysfunction. Five of 13 patients (38%) with self-reported pretreatment potency (International Index of Erectile Function >17) remained potent. Clinically relevant quality of life deterioration was reported for only 6 of 31 items and was not statistically significant. Biochemical failure (nadir + 2) occurred in 26 patients. Among intraprostatic recurrences, 73% were in field. After 2.5 years, biochemical disease-free survival was 51% (95% confidence interval, 37%-69%), metastases-free survival was 75% (64%-89%), androgen deprivation therapy-free survival was 90% (82%-99%), and overall survival was 98% (94%-100%). Presalvage PSA, CTV size, and stage ≥T3 were significantly associated with biochemical failure. Higher-risk patients (stage ≥T3, PSA ≥10, or PSA double time ≤9 months) had 25% biochemical disease-free survival at 2.5 years versus 71% for lower-risk patients. At this early stage, MRI-guided ultrafocal HDR-BT seems to be a safesalvage treatment option, with acceptable biochemical control in a well-selected group of patients and potential for effectively postponing androgen deprivation therapy.

Salvage CyberKnife-Based Reirradiation of Patients With Recurrent Prostate Cancer: The Single-Center Experience.

The aim of this study was to evaluate CyberKnife-based radioablation as a salvage treatment for prostate cancer postirradiation relapses based on a group of patients disqualified from available conventional methods of salvage treatment. Thirty-eight patients were treated with a fraction dose varying from 5.5 to 10 Gy (median 7.35) to a total dose of 18 to 36.25 Gy (median 36.25). In all, 55.3% of patients had androgen deprivation therapy during this time. Nine patients had oligometastases in the salvage time. The follow-up varied from 1.6 to 46.4 months (mean 19.7, median 14.4). In all, 92.6% to 97.4% of patients had no gastrointestinal acute adverse effects; no effects higher than G1 were noted. There were particular (up to 4.8%) G2 late gastrointestinal effects. The percentage without genitourinary acute effects varied from 59.1% to 78.9%; 3.7% had G3 toxicity. G3 late genitourinary toxicity appeared 3 times, the maximal percentage being 12.5% (24 months after salvage treatment). The nadir of prostate-specific antigen median was 0.24 ng/mL (9 months after treatment). Twelve (31.6%) patients failed in the timeline of 6 to 42 months after salvage treatment (mean 18.7, median 16.5)—5 due to dissemination. In 2 cases, progression in existing metastases was identified. Five (13.2%) patients had biochemical failure without additional metastases (local relapses); hence, local control was 86.8%. The failure risk is strongly influenced by initial disease stage and presalvage prostate-specific antigen concentration. The obtained results permit us to conclude that such a treatment could be an effective and safe option for prostate cancer postirradiation relapse salvage treatment.

Development and internal validation of prediction models for biochemical failure and composite failure after focal salvage high intensity focused ultrasound for local radiorecurrent prostate cancer: Presentation of risk scores for individual patient prognoses

PurposePatient selection for focal salvage remains difficult. Therefore, we developed and internally validated prediction models for biochemical failure (BF) and a composite endpoint (CE) following focal salvage high intensity focused ultrasound (HIFU) for radiorecurrent prostate cancer. Materials and methodsA prospective HIFU registry identified 150 cases (November 2006–August 2015). Recurrence was assessed with multiparametric magnetic resonance imaging (MRI) combined with template prostate mapping biopsies, targeted biopsies, or systematic transrectal ultrasound-guided biopsies. Metastatic disease was ruled out with a positron emission tomography-computed tomography and a bone scan. Focal salvage HIFU consisted of quadrant-ablation, hemi-ablation, or index-lesion ablation. Cox-regression was used for BF (Phoenix-definition) and CE (BF/MRI+/biopsies+/local or systemic treatment/metastases+/prostate cancer specific mortality+). Internal validation was performed using bootstrap resampling (500 datasets) after which C-statistic and hazard ratios were adjusted. Models were calibrated and risk scores created. ResultsMedian follow-up was 35 months (interquartile range: 22–52). Median biochemical disease-free survival (DFS) was 33 months (95% CI: 23–45). Median CE-free survival was 24 months (95% CI: 21–35). After multivariable analysis, DFS interval after primary radiotherapy, presalvage prostate-specific antigen (PSA), PSA-doubling time, prostatic volume, and T-stage (both MRI based) predicted BF. For the CE, PSA-doubling time was not predictive but additionally, primary Gleason score was. The adjusted C-statistics were 0.68 and 0.64 for BF and CE, respectively. Calibration was accurate until 48 months. The risk scores showed 3 groups, with biochemical DFS of 60%, 35%, and 7% and CE-free survival of 40%, 24%, and 0% at 4 years. ConclusionOur model, once externally validated, could allow for better selection of patients for focal salvage HIFU.

Prostate Specific Antigen Nadir of 0.1 or Less Is a Predictor of Treatment Success in Men Undergoing Salvage Whole Prostate Gland Cryoablation.

To assess factors that affect prostate biopsy results following salvage whole gland cryoablation. One hundred seventy-four patients underwent prostate biopsy following salvage whole gland cryoablation of the prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and χ2 tests and logistic regression analysis were used to assess predictors of positive biopsy. Prostate specific antigen (PSA) nadir was divided into a statistical tertile for comparisons between different nadir PSA cut points. Fifty-two of 174 (29.9%) of this highly select group of men who underwent biopsy had a posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy following salvage therapy had significantly higher median nadir PSA, shorter median time to prostate biopsy, and shorter median time to biochemical failure. Compared to the lowest tertile (PSA nadir defined as ≤0.1 ng/mL), PSA in the second tertile (0.11-0.8 ng/mL) and third tertile (>0.8 ng/mL) demonstrated increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI] 1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in adjusted models. In addition, men with a presalvage PSA >20 (OR 7.65; 95% CI 2.03, 28.9; p = 0.003) and Gleason score ≥8 (OR 2.26; 95% CI 0.93, 5.47; p = 0.07) had a higher OR of positive biopsy. Nadir PSA of 0.1 ng/mL or less following salvage cryotherapy is predictive of treatment success. Routine biopsy should be reserved for men with nadir PSA >0.1 ng/mL and patients with high risk features of prostate cancer before salvage cryoablation.

Salvage of locally recurrent prostate cancer after external beam radiation using reduced-dose brachytherapy with neoadjuvant plus adjuvant androgen deprivation

PurposeLocal recurrence (LR) of prostate cancer after external beam radiotherapy (EBRT) is a serious problem. Our purpose was to determine if reduced-dose salvage brachytherapy could achieve high rates of biochemical control with acceptable toxicity if combined with androgen deprivation therapy (ADT). Methods and MaterialsThirty-three consecutive patients with LR after EBRT were treated with salvage brachytherapy plus ADT from 1998 to 2013. All had pathologically confirmed LR, disease-free interval ≥18 months after EBRT, no distant/nodal metastasis, and International Prostate Symptom Score ≤15. Whole-gland salvage treatment was delivered using low-dose-rate (median 100 Gy with 103Pd, n = 25) or high-dose-rate brachytherapy (30 Gy in 6 fractions over 4 weeks, n = 8) plus 4–6 months of neoadjuvant plus adjuvant ADT. ResultsFifty-five percent had high-risk disease at diagnosis. Median EBRT dose was 70.2 Gy; median prostate-specific antigen nadir was 0.8 ng/mL. Median time to recurrence was 56 months; median presalvage prostate-specific antigen was 5.0 ng/mL. Median postbrachytherapy followup was 61 months (range 7–150 months). Five and 7-year relapse-free survival, distant metastasis-free survival, and overall survival were 79% and 67%; 93% and 86%; and 94% and 85%, respectively. Freedom from late Grade 3 GU toxicity at 5 years was 85%. There were no late Grade ≥2 GI toxicities. ConclusionsThis is the largest series of salvage brachytherapy combined with neoadjuvant plus adjuvant ADT and uses reduced-dose brachytherapy. Results suggest that reduced-dose salvage brachytherapy is feasible and reasonably well tolerated when combined with ADT. Compared to prior series, this approach was associated with favorable relapse-free survival. Prospective studies of reduced-dose salvage brachytherapy plus ADT are warranted.

A Retrospective Feasibility Study of Salvage Pelvic Nodal Radiation in 6 Patients With Biochemical Failure Following Prostate Fossa Radiation: An Alternative to Androgen Deprivation Therapy (ADT).

To evaluate salvage pelvic nodal radiation as an alternative to androgen deprivation therapy (ADT) in patients with biochemical failure and lymph node recurrence following salvage prostate fossa radiation. Six patients with biochemical failure and lymph node recurrence following prostate fossa radiation were treated with salvage pelvic nodal radiation therapy. A gross target volume was contoured using Choline PET/CT, CT, or MRI imaging. The clinical target volume included pelvic nodes. Avoidance structures were created using isodose lines from previous prostate fossa radiation plans. Radiation was delivered using IMRT or VMAT techniques. Failure was defined as a confirmed rise of prostate-specific antigen (PSA) over 0.2 ng/mL. Four patients had presalvage PSA values <1 and 2 patients had PSAs >1. Dose to the clinical target volume was 54 to 60 Gy. The gross target volume dose was 60 to 73.6 Gy. One of the 2 patients with a high PSA received 6 months of concomitant ADT. Mean follow-up after RT for all patients was 24.9 months (range, 18.1 to 33.0 mo). All 5 patients with no ADT had significant PSA responses. PSA reduction was 80% (62% to 100%) of pre-RT PSA. At last follow-up, 2 patients with initial PSA<1 ng/mL remain free of biochemical progression at 33 and 20 months. Four patients have had PSA rise and meet criteria for failure. This included both patients with initial PSA values > 1. Duration of response before failure was 18.1 to 30.7 months. ADT for failure has been started in 1 patient. There was no grade ≥2 GI or GU toxicity. Salvage lymph node irradiation for patients with early biochemical recurrence and radiologic evidence of pelvic nodal metastases is well tolerated and associated with a durable biochemical response and may be an alternative to or may delay the need for ADT in some patients.

Five-Year Biochemical Progression-Free Survival Following Salvage Whole-Gland Prostate Cryoablation: Defining Success with Nadir Prostate-Specific Antigen.

Salvage prostate cryoablation is an effective treatment for patients with localized prostate cancer relapse following primary radiotherapy. The postsalvage prostate-specific antigen (PSA) nadir that best predicts long-term biochemical progression-free survival (bPFS) is not yet defined. We sought to determine what nadir PSA best predicted success following salvage whole-gland cryoablation. We retrospectively reviewed a cohort of 486 hormone-naive patients who underwent salvage whole-gland cryoablation from the Cryo On-Line Database (COLD). Studied variables were age, race, initial PSA, presalvage prostate-specific antigen (psPSA), initial Gleason score, Gleason score at presalvage biopsy, clinical stage, and follow-up PSA values. Kaplan-Meier (KM) analysis was used to calculate 5-year bPFS using the Phoenix criteria. Hazard ratio and relative risk were also analyzed. Differences among the KM estimates, at 5 years, were calculated using the log-rank test. Using group thresholds, KM analysis identified nadir PSA less than or greater than 0.4 ng/mL as the nadir PSA threshold, with the greatest difference in bPFS. The KM estimated 5-year bPFS was 75.5% and 22.1% for nadir PSA <0.4 and ≥0.4 ng/mL, respectively. Stratified by psPSA, the KM estimated 5-year bPFS comparing patients with PSA nadir <0.4 vs ≥0.4 ng/mL was 78.5% and 17.9% (p < 0.0001) for psPSA <4 ng/mL, 77.1% and 15.7% (p < 0.0001) for psPSA 4-10 ng/mL, and 77.8% and 16.8% (p < 0.0001) for psPSA >10 ng/mL, respectively. The best objective indicator of biochemical success following whole-gland salvage cryoablation of the prostate is PSA nadir <0.4 ng/mL.

Development and internal validation of a multivariable prediction model for biochemical failure after whole-gland salvage iodine-125 prostate brachytherapy for recurrent prostate cancer

BackgroundLocalized recurrent prostate cancer after primary radiotherapy can be curatively treated using salvage iodine-125 (125I) brachytherapy. Selection is hampered by a lack of predictive factors for cancer control. This study aims to develop and internally validate a prognostic model for biochemical failure (BF) after salvage 125I brachytherapy. Methods and MaterialsWhole-gland salvage 125I brachytherapy patients were treated between 1993 and 2010 in two radiotherapy centers in the Netherlands. Multivariable Cox regression was performed to assess the predictive value of clinical parameters related to BF (Phoenix-definition [prostate-specific antigen [PSA]-nadir + 2.0 ng/mL]). Missing data were handled by multiple imputation. The model's discriminatory ability was assessed with Harrell's C-statistic. Internal validation was performed using bootstrap resampling (2000 data sets). Goodness-of-fit was evaluated with calibration plots. All analyses were performed using the recently published TRIPOD (Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) statement. ResultsAfter median followup of 74 months (range 5–138), 43 of a total 62 patients developed BF. In multivariable analysis, disease-free survival interval (DFSI) after primary therapy and pre-salvage prostate-specific antigen doubling time (PSADT) were predictors of BF: corrected hazard ratio (HR) 0.99 (95% confidence interval 0.97–0.999; p = 0.04) and 0.94 (95% confidence interval 0.89–0.99; p = 0.03), both for a 1-month increase (optimism-adjusted C-statistic 0.70). Calibration was accurate up to 36 months. Of patients with PSADT >30 months and DFSI >60 months, 36-month biochemical disease-free survival was >75%. Every 12-month increase in DFSI will allow 3-month decrease in PSADT while maintaining the same biochemical recurrence-free rates. ConclusionsWe have presented results from a cohort of patients undergoing salvage 125I-brachytherapy. Our data show that better selection of patients is possible with the DFSI and PSADT.

The Effect of Androgen Deprivation Therapy Before Salvage Whole-gland Cryoablation After Primary Radiation Failure in Prostate Cancer Treatment

To define the effects of androgen deprivation therapy (ADT) used prior to salvage cryoablation (SC) for the treatment of recurrent localized prostate cancer after radiation. Patients from the Cryo On-Line Database registry undergoing SC after radiation failure were divided according to whether they had previously received or not received ADT. Baseline characteristics including demographics and presalvage cancer risk were compared. Biochemical progression-free survival (bPFS) as defined by the Phoenix criteria was compared between the 2 groups as a whole and also in D'Amico risk-stratified subgroups. In addition, postsurgical complications such as urinary fistula, retention, incontinence, and erectile dysfunction were compared. Two groups consisting of 254 and 486 patients with and without pre-SC ADT were analyzed. The patients who received ADT were younger (P = .003) and had higher presalvage D'Amico risks (P <.001). The 5-year bPFS was 63.8% and 39.3% for the hormone-naïve and the pre-SC ADT patients, respectively (P <.001). On subgroup analysis, the difference in 5-year bPFS was significant only for patients with a high D'Amico cancer risk (54.3% vs 30.5%; P = .013). On multivariate analysis, presalvage prostate-specific antigen (hazard ratio [HR], 1.7), Gleason score ≥ 8 (HR, 2.5), and use of pre-SC ADT (HR, 1.7) correlated with biochemical recurrence. Additionally, patients receiving pre-SC ADT experienced less urinary retention (P = .001) and incontinence (P = .008) but were more likely to be impotent (P = .010). Patients receiving ADT before SC, especially those with high-risk prostate cancer, had worse 5-year bPFS. Added caution is needed when selecting patients having previously received ADT for salvage cryotherapy.

Safety and efficacy of salvage low-dose-rate brachytherapy for prostate bed recurrences following radical prostatectomy.

PurposeTo report efficacy in our series of nodular recurrences in the post-surgical bed that underwent salvage low-dose-rate (LDR) brachytherapy.Material and methodsPatients with radical prostatectomy (RP) who had biochemical failure with nodular recurrence detected by DRE, ultrasound, and pelvic CT and then salvaged with LDR 125I brachytherapy were included. Nodular recurrences were biopsy confirmed adenocarcinoma, and patients had no evidence of nodal or distant metastasis on imaging including bone scan. Follow up was at least every 6 months with a serial prostate specific antigen (PSA).ResultsTwelve patients had salvage LDR brachytherapy with median age 69 years (range 59-86) and median pre-salvage PSA of 4.22 ng/ml. Nodule biopsy Gleason score was 7, 8, or undifferentiated. Median rectal V100 was 0.00 cc. Compared to pre-salvage, patients reported no additional genitourinary (GU) toxicity. After a median 35 months post-salvage follow up (range 10-81 months), patients had a median PSA nadir of 0.72 ng/ml (range 0.01-22.4). At 6 months post salvage, 90% of patients had a PSA below pre-salvage levels. At last follow up, 4 patients had PSA control.ConclusionsThere was a trend to improved biochemical relapse free survival for lower Gleason score and pre-salvage PSA, which may be indicative of the lack of or only low volume metastatic disease. LDR brachytherapy is an effective salvage technique and can be considered in well selected patients allowing for dose escalation to the nodular recurrence.

Salvage brachytherapy in prostate local recurrence after radiation therapy: predicting factors for control and toxicity.

PurposeTo evaluate efficacy and toxicity after salvage brachytherapy (BT) in prostate local recurrence after radiation therapy.Methods and materialsBetween 1993 and 2007, we retrospectively analyzed 56 consecutively patients (pts) undergoing salvage brachytherapy. After local biopsy-proven recurrence, pts received 145 Gy LDR-BT (37 pts, 66%) or HDR-BT (19 pts, 34%) in different dose levels according to biological equivalent doses (BED2 Gy). By the time of salvage BT, only 15 pts (27%) received ADT. Univariate and multivariate analyses were performed to identify predictors of biochemical control and toxicities. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCv3.0).ResultsMedian follow-up after salvage BT was 48 months. The 5-year FFbF was 77%. HDR and LDR late grade 3 GU toxicities were observed in 21% and 24%. Late grade 3 GI toxicities were observed in 2% (HDR) and 2.7% (LDR). On univariate analysis, pre-salvage prostate-specific antigen (PSA) > 10 ng/ml (p = 0.004), interval to relapse after initial treatment < 24 months (p = 0.004) and salvage HDR-BT doses BED2 Gy level < 227 Gy (p = 0.012) were significant in predicting biochemical failure. On Cox multivariate analysis, pre-salvage PSA, and time to relapse were significant in predicting biochemical failure.HDR-BT BED2 Gy (α/β 1.5 Gy) levels ≥ 227 (p = 0.013), and ADT (p = 0.049) were significant in predicting grade ≥ 2 urinary toxicity.ConclusionsProstate BT is an effective salvage modality in some selected prostate local recurrence patients after radiation therapy. Even, we provide some potential predictors of biochemical control and toxicity for prostate salvage BT, further investigation is recommended.

Treatment of Prostate Cancer Local Recurrence After Whole-Gland Cryosurgery With Frameless Robotic Stereotactic Body Radiotherapy: Initial Experience

BackgroundThe use of frameless robotic stereotactic body radiotherapy has not been investigated in patients whose primary cryosurgery treatment failed. The aim of this series was to present initial experiences with frameless robotic radiosurgery in the treatment of local prostate recurrence after cryotherapy. MethodsWe reviewed the outcome of frameless robotic radiosurgery in 4 patients for biopsy-proven local recurrent prostate cancer after cryotherapy. The patients underwent stereotactic body radiation therapy (SBRT) at Winthrop University Hospital, Mineola, New York. ResultsThe patients' ages ranged from 66 to 75 years old. The average follow-up was more than 4 months. Presalvage prostate-specific antigen (PSA) levels were 7.3, 11.9, 6.1, and 20.9 ng/mL for the four patients. Presalvage Gleason scores were 7, 7, 9, and 8 respectively. One patient had insufficient follow-up for inclusion. The 3 remaining patients showed reduction of PSA levels after SBRT. Follow-up post-SBRT PSA levels were 2.2, 0.19, and 2.0 ng/mL. The average PSA reduction was 7.0 ng/mL. Morbidity at 3-week follow-up included urinary urgency, dysuria, and constipation. There was no change in international prostate symptom score or The International Consultation on Incontinence Questionnaire-Short Form scores after SBRT. One patient experienced erectile dysfunction from SBRT. ConclusionsInitial results indicate that robotic SBRT is a viable option for patients who have failed initial cryosurgery therapy measures. The patients had minimal morbidity with significant reduction in PSA levels.

Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7years: 90% vs. 79.1%, p = 0.07). Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses ≥70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied.

Disease-Free Survival Following Salvage Cryotherapy for Biopsy-Proven Radio-Recurrent Prostate Cancer

BackgroundThe optimum treatment of prostate cancer recurrence following radiation therapy (RT) remains controversial due to the lack of long-term data. ObjectiveOur aim was to review the survival of patients who underwent salvage cryotherapy to the prostate gland for biopsy-proven recurrent prostate cancer and establish prognostic indicators. Design, setting, and participantsA retrospective analysis was performed on all patients undergoing salvage cryotherapy at an academic urology unit for biopsy-proven locally recurrent prostate cancer after RT from 1995 to 2004. Patients’ preoperative, perioperative, and postoperative data were reviewed and recorded. InterventionTwo freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon. MeasurementsThe primary outcome was survival. Secondary outcomes were disease-free survival (DFS), metastasis-free survival, and progression to androgen-deprivation therapy. Results and limitationsOf 187 patients, 176 had records available for follow-up (follow-up rate: 94%). Mean follow-up was 7.46 yr (range: 1–14 yr). Fifty-two patients were followed for >10 yr. DFS at 10 yr was 39%. Risk factors for recurrence were presalvage prostate-specific antigen (PSA), preradiation, and presalvage Gleason score. A PSA nadir >1.0 ng/dl was highly predictive of early recurrence. ConclusionsSalvage cryotherapy led to an acceptable 10-yr DFS. Presalvage PSA and Gleason score were the best predictors of disease recurrence. A PSA nadir >1 ng/dl following cryotherapy indicated a poor prognosis, and recurrence of disease was universal in these patients.

Early hypofractionated salvage radiotherapy for postprostatectomy biochemical recurrence

Postprostatectomy adjuvant or salvage radiotherapy, when using standard fractionation, requires 6.5 to 8 weeks of treatment. The authors report on the safety and efficacy of an expedited radiotherapy course for salvage prostate radiotherapy. A total of 108 consecutive patients were treated with salvage radiation therapy to 65 grays (Gy) in 26 fractions of 2.5 Gy. Median follow-up was 32.4 months. Median presalvage prostate-specific antigen (PSA) was 0.44 (range, 0.05-9.50). Eighteen (17%) patients received androgen deprivation after surgery or concurrently with radiation. The actuarial freedom from biochemical failure for the entire group at 4 years was 67% ± 5.3%. An identical 67% control rate was seen at 5 years for the first 50 enrolled patients, whose median follow-up was longer at 43 months. One acute grade 3 genitourinary toxicity occurred, with no acute grade 3 gastrointestinal and no late grade 3 toxicities observed. On univariate analysis, higher Gleason score (P = .006), PSA doubling time ≤12 months (P = .03), perineural invasion (P = .06), and negative margins (P = .06) showed association with unsuccessful salvage. On multivariate analysis, higher Gleason score (P = .057) and negative margins (P = .088) retained an association with biochemical failure. Hypofractionated radiotherapy (65 Gy in 2.5 Gy fractions in about 5 weeks) reduces the length of treatment by from 1-½ to 3 weeks relative to other treatment schedules commonly used, produces low rates of toxicity, and demonstrates encouraging efficacy at 4 to 5 years. Hypofractionation may provide a convenient, resource-efficient, and well-tolerated salvage approach for the estimated 20,000 to 35,000 US men per year experiencing biochemical recurrence after prostatectomy.

Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with (103)Pd or (125)I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade > or = 2 toxicity (p = 0.03). With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

Salvage Hypofractionated Radiotherapy for Biochemically Recurrent Prostate Cancer After Radical Prostatectomy

To evaluate whether hypofractionation is well tolerated and to preliminarily assess biochemical control of this regimen in a postprostatectomy, salvage setting. A retrospective analysis was performed in 50 patients treated between May 2003 and December 2005 with hypofractionated radiotherapy for biochemical recurrence after radical prostatectomy. Radiotherapy was prescribed to the prostatic fossa to 65-70 Gy in 26-28 fractions of 2.5 Gy each, using intensity-modulated radiotherapy with daily image localization. Toxicities were scored using a modified Radiation Therapy Oncology Group scale and the Fox Chase modification of Late Effects Normal Tissue scale. The median follow-up was 18.9 months (range, 5.3-35.9). No Grade 3 or greater acute or late toxicities were observed. Grade 2 toxicities included four acute genitourinary, one acute gastrointestinal, two late genitourinary, and two late gastrointestinal toxicities. Of the 50 patients, 39 demonstrated a continuous biochemical response after salvage therapy, 3 had an initial response before prostate-specific antigen failure, and 7 had prostate-specific antigen progression, 1 of whom died of progressive metastatic disease. Finally, 1 patient discontinued therapy because of the diagnosis of a metachronous pancreatic cancer and died without additional prostate cancer follow-up. All remaining patients were alive at the last follow-up visit. A lower presalvage prostate-specific antigen level was the only significant prognostic factor for improved biochemical control. The estimated actuarial biochemical control rate at 2 years was 72.9%. The toxicity and early biochemical response rates were consistent with expectations from conventional fractionation. Additional follow-up is required to better document the biochemical control, but these results suggest that hypofractionation is a well-tolerated approach for salvage radiotherapy.

Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate‐specific antigen failure

Among men who experience prostate-specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local-only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local-only failure initially have low-risk disease (PSA < 10 ng/mL, Gleason score < or =6, clinical T1c or T2a tumor status), pretreatment PSA velocity < 2.0 ng/mL per year at the time of initial presentation, interval to PSA failure > 3 years, PSA doubling time > 12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels > 10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores > or =7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post-RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local-only recurrences after radiation therapy.

Presalvage prostate-specific antigen (PSA) and PSA doubling time as predictors of biochemical failure of salvage cryotherapy in patients with locally recurrent prostate cancer after radiotherapy.

The value of presalvage cryotherapy serum PSA level in predicting biochemical failure in patients with local recurrence of prostate cancer (PCa) after radiotherapy was documented; however, little is known about the predictive value of prostate-specific antigen (PSA) doubling time (DT) in this patient group. The purpose of the current study was to evaluate serum PSA level and PSA DT as predictors of salvage cryotherapy outcomes in patients being treated for postradiotherapy locally recurrent PCa. The charts of patients treated with salvage cryotherapy were retrospectively reviewed for locally recurrent PCa at the M. D. Anderson Cancer Center from January 1980 to July 2004. Patients who received neoadjuvant or adjuvant hormone therapy were excluded. We assessed pre- and postradiotherapy clinical data, pre- and postsalvage cryotherapy clinical data, and other variables. Kaplan-Meier and log rank tests were performed to assess unadjusted survival probabilities and 2-group survival comparisons, respectively. Cox proportional hazards regression models were used to assess the effect of patient characteristics in predicting overall, disease-specific, and biochemical failure-free survival. Forty-nine patients met the eligibility criteria. The median age of patients at diagnosis was 66 years (58-81 years) with the initial clinical stage before radiotherapy most commonly T2 (n = 25) or T3 (n = 21). The median presalvage cryotherapy serum PSA level was 5.9 ng/mL (0.4-23.1 ng/mL) and the presalvage prostatic biopsies were frequently high grade (Gleason grade > or =8 in 51% of patients). The median postsalvage cryotherapy serum PSA level was 0.1 ng/mL (0.1-9.5 ng/mL), and biochemical failure (defined as a serum PSA level > or =2 ng/mL above the postsalvage cryotherapy PSA nadir) occurred in 26 patients. In these 26 patients, there was a statistically significant difference between pre- and postsalvage cryotherapy PSA DTs (12.3 months to 5.6 months, respectively; P = .02). A presalvage cryotherapy serum PSA level >10 ng/mL (P = .002) and PSA DT < or =16 months (P = .06) were found to predict the subsequent risk of biochemical failure. Presalvage PSA and PSA DT can predict biochemical failure of salvage cryotherapy, although the predictive value of PSA DT only trended toward significance. The statistically significant difference in pre- and postsalvage cryotherapy PSA DTs was reflective of aggressive tumor biology.