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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Hypofractionated stereotactic body radiotherapy in low-risk prostate adenocarcinoma: preliminary results of a multi-institutional phase 1 feasibility trial

BACKGROUND:

Recent reports using extreme hypofractionated regimens in the treatment of low‐risk prostate adenocarcinoma have been encouraging. Here, the authors report on their own multi‐institutional experience with extreme hypofractionated stereotactic radiotherapy for early stage disease.

METHODS:

In total, at 4 centers, 45 patients with National Comprehensive Cancer Network‐defined, low‐risk prostate adenocarcinoma were enrolled in a phase 1, multi‐institutional trial of hypofractionated radiosurgery with a proprietary radiosurgical device (CyberKnife). Thirty‐four patients received 7.5 grays (Gy) delivered in 5 fractions, 9 patients received 7.25 Gy delivered in 5 fractions, and 2 patients received other regimens. The variables evaluated were biochemical progression‐free survival (bPFS), prostate‐specific antigen (PSA) bounce, and toxicities. Health‐related quality of life was evaluated using the Sexual Health Inventory for Men (SHIM), American Urological Association (AUA), and Expanded Prostate Cancer Index Composite (EPIC) questionnaires.

RESULTS:

The median follow‐up for surviving patients was 44.5 months (range, 0‐62 months). The bPFS rate at 3 years was 97.7%. The median PSA declined from 4.9 ng/mL at diagnosis to 0.2 ng/mL at last follow‐up, and the median percentage PSA decline at 12 months was 80%. Nine patients experienced at least 1 PSA bounce ≥0.4 ng/mL, and 4 patients experienced 2 PSA bounces. The median time to first PSA bounce was 11.6 months (range, 7.2‐18.2 months), and the mean percentage PSA bounce was 1.07 ng/mL. There was 1 episode of late grade 3 urinary obstruction, and there were 2 episodes of late grade 3 proctitis. There was a significant late decline in SHIM and EPIC sexual scores and a small, late decline in the EPIC Bowel domain score.

CONCLUSIONS:

In a select population, extreme hypofractionation with stereotactic radiosurgery was safe and effective for the treatment of low‐risk prostate adenocarcinoma. Cancer 2012. © 2011 American Cancer Society.     

Real World Experience With Pembrolizumab in Recurrent or Advanced Prostate Cancer

IntroductionPhase II trials have shown activity with pembrolizumab against prostate cancer. However, the clinical factors predictive of a response to pembrolizumab in men with prostate cancer are unknown.Patients and MethodsA total of 54 consecutive men with progressive, recurrent, or advanced prostate cancer were treated with 1 to 12 cycles of pembrolizumab 200 mg every 3 weeks with or without stereotactic body radiotherapy (SBRT).ResultsFor the 31 men evaluable for response, the median age, prostate-specific antigen (PSA) level, and Gleason score were 75 years, 30 ng/mL, and 8 (4 + 4), respectively, which were similar to those for the 23 nonevaluable patients. The treatments received before pembrolizumab were enzalutamide in 26, abiraterone in 18, and sipuleucel-T in 23. All but 4 men had had castrate-resistant disease. Of the 54 men, 31 had completed ≥ 4 cycles of pembrolizumab and were evaluable for the response. Ten men had undergone SBRT to an isolated metastasis shortly before or during pembrolizumab treatment, with the goal of inducing an abscopal effect. The clinical characteristics of the 17 men with a response or stable disease were compared with those of the 14 men with progressive disease. Grade ≥ 2 toxicity occurred in 16 men (30%). PSA stabilization or a response occurred in slightly more than one half (55%) of the men treated with ≥ 4 cycles of pembrolizumab. Five patients had a notable PSA decline of > 50%, which were sustained as long as they had continued receiving pembrolizumab. A PSA response or stabilization was more common for men who had begun taking pembrolizumab with a lower PSA level, fewer bone metastases, and fewer mutations and without previous chemotherapy. A statistically nonsignificant trend toward stabilization or a response was observed in men who had undergone concomitant SBRT.ConclusionPembrolizumab showed modest anticancer activity against metastatic castrate-resistant prostate cancer. A PSA response or stabilization occurred more frequently in men with less-advanced disease.     

Salvage cryosurgery for recurrent prostate cancer after radiation therapy: a seven-year follow-up

Cryosurgery of the prostate presents as an efficient therapy following failed radiation therapy. We report on a 7-year retrospective analysis evaluating the morbidity adn biochemical disease-free survival(bDFS) of this therapy. Between 1993 and 2001, 59 patients who had been previously treated with radiation therapy and had rising serum prostate-specific antigen(PSA) values underwent salvage cryoablation of the prostate for localized, histologically proven, recurrent prostate cancer. Serial serum PSA testing was performed, and biopsies were taken at 6, 12, and 24 months, and again at 5 years, and any time the PSA rose above 0.5 ng/mL. Patients were stratified along clinical parameters. The combined postsalvage bDFS rate using a PSA cutoff of 0.5 ng/mL was 59% and 69% with a 1.0 ng/mL PSA cut off. Using a PSA threshold of 0.5 ng/mL as evidence of biochemical recurrence, 61%, 62%, and 50% of patients with <4 ng/mL, 4-10 ng/mL, and > 10 ng/mL PSA, respectively, remain biochemically relapse free at 7 years. A threshold of 1.0 ng/mL yielded a disease-free status of 78%, 74%, and 46% respectively. Patients biopsies showed no evidence of residual or recurrent disease. Improved survival rates and no known latent complications indicate cryosurgery is a promising form of treatment for radiation-resistant prostate cancer. This 7-year analysis shows a promising validation of cryosurgery as an efficacious treatment modality for locally confined T1-T3 prostate cancer following primary radiation therapy failure.     

Metastasis-directed Therapy (SBRT) Guided by PET-CT 18F-CHOLINE Versus PET-CT 68Ga-PSMA in Castration-sensitive Oligorecurrent Prostate Cancer: A Comparative Analysis of Effectiveness

BackgroundThe present analysis aims to compare the impact of 18F-fluorocholine (¹⁸F-choline) and gallium-68 prostate-specific membrane antigen (⁶⁸Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)–guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC).Materials and MethodsInclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by ¹⁸F-choline or ⁶⁸Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered.ResultsA total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent ⁶⁸Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the ⁶⁸Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PET–guided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with ⁶⁸Ga-PSMA-based SBRT.ConclusionIn the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the ¹⁸F-choline-PET cohort. Randomized trials are advocated.     

Salvage Stereotactic Body Radiotherapy for Patients With Limited Prostate Cancer Metastases: Deferring Androgen Deprivation Therapy

BackgroundWe investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases.Patients and MethodsPatients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events.ResultsWe treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression-free survival was 100% and 42%, respectively. Eleven and 3 patients, respectively, required a second and third salvage treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed.ConclusionRepeated salvage SBRT is feasible, well tolerated and defers palliative ADT with a median of 38 months in patients with limited bone or lymph node PCa metastases.     

Salvage cryotherapy for recurrent prostate cancer after radiotherapy: variables affecting patient outcome.

PURPOSE: To determine the long-term disease-specific survival (DSS) and disease-free survival (DFS) rates after salvage cryotherapy for locally recurrent adenocarcinoma of the prostate and to identify pretreatment factors that have an impact on DSS and DFS. PATIENTS AND METHODS: Between July 1992 and January 1995, 131 patients who had received definitive radiation therapy (XRT) underwent salvage cryotherapy for locally recurrent adenocarcinoma of the prostate. Cryotherapy failure was defined as an increasing postcryotherapy prostate-specific antigen (PSA) level of > or = 2 ng/mL above the postcryotherapy nadir, a positive prostate biopsy, or radiographic evidence of metastatic disease. Clinical variables were studied to determine whether there was an association with the DSS and DFS. RESULTS: The median follow-up was 4.8 years. The 5-year DSS rates were 87% for patients with a precryotherapy Gleason score < or = 8 and 63% for those with Gleason scores of 9 and 10 (P =.012). The 5-year DFS rates were 57% for patients with a precryotherapy PSA level of < or = 10 ng/mL and 23% for those with a PSA level greater than 10 ng/mL (P =.0004). The 5-year DSS rates for patients with a pre-XRT clinical stage of T1 to T2 and those with a clinical stage of T3 to T4 were 94% and 72%, respectively (P =.0041). The 5-year DFS rates for these groups were 90% and 69%, respectively (P =.0057). CONCLUSION: Androgen-independent local recurrences, Gleason score, and pre-XRT clinical stage were important factors that had an impact on DSS and DFS. The subset of patients cured by salvage cryotherapy seems to be small, and patient selection is important.     

Stereotactic body radiotherapy for castration-sensitive prostate cancer bone oligometastases

To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naïve disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan–Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0–67.2 months). No acute or late toxicity of grade?>?1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT.     

Salvage Intensity-Modulated Radiation Therapy for Locally Recurrent Prostate Cancer After Cryotherapy

BackgroundTo summarize our results of intensity-modulated radiation therapy (IMRT) for prostate adenocarcinoma after cryotherapy failure.Materials and MethodsPatients underwent IMRT with curative intent for biochemically recurrent prostate cancer after cryotherapy. Radiation was delivered to a minimum dose of 72 Gy (range, 72-81 Gy). Acute and late treatment-related gastrointestinal and genitourinary effects were scored according to Common Toxicity Criteria version 3.0. Prostate-specific antigen failure was defined by Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology 2006 consensus definition.ResultsNine patients were treated from 2008 to 2010. The median follow-up was 31 months (range, 15-40 months). The mean preradiotherapy prostate-specific antigen was 4.3 ng/mL (range, 1.07-15.6 ng/mL). The median elapsed time between cryotherapy and IMRT was 20.5 months (range, 8.5-56.5 months). Biochemical control was achieved in 7 patients. Two patients developed distant metastases shortly after completion of radiotherapy. No patients experienced grade 3 or higher toxicities.ConclusionsOur results suggest that high-dose IMRT after cryotherapy failure is well tolerated, without severe morbidity. The results also showed that IMRT can render a significant number of patients biochemically free of disease after initial cryotherapy. High-dose IMRT should be considered as a treatment option for these potentially salvageable cases.     

Salvage Prostate Cryoablation for the Management of Local Recurrence After Primary Cryotherapy: A Retrospective Analysis of Functional and Intermediate-Term Oncological Outcomes Associated With a Second Therapeutic Freeze

BackgroundThe purpose of the study was to examine the outcomes of salvage prostate cryoablation for managing patients with local recurrence after primary cryotherapy.Patients and MethodsThe records of 108 patients treated with salvage prostate cryoablation for biopsy-proven local recurrence after primary cryotherapy were retrospectively reviewed. Oncological outcome was defined by the rate of biochemical recurrence (BCR) after salvage ablation using Phoenix criteria.ResultsWhole-gland (n = 91; 84.3%) or focal (n = 17; 15.7%) salvage cryoablation after failed primary cryosurgery were used. Fifty-eight of 108 patients (53.7%) had received androgen deprivation therapy (n = 35; 32.4%)/radiotherapy (n = 23; 21.3%) before salvage ablation. Two-year and 5-year BCR rates after salvage therapy were 28.2% and 48.3%, respectively. In univariate analysis, a higher Gleason score, D’Amico risk category (P < .0001) as well as prostate-specific antigen density >0.15 ng/mL/cc (P = .02) before second cryotherapy were significantly associated with the risk of BCR. In multivariable analysis, the only significant factor associated with risk of BCR after the second ablation was a higher presalvage D’Amico risk category (P = .008). Persistent urinary incontinence (1-4 pads per day) in 8 (7.4%), temporary urinary retention in 4 (3.7%), and rectourethral fistula in 4 (3.7%) patients were reported 1 year after second cryoablation. During the same period, 13.8% of patients were able to have either spontaneous or medication-augmented erections sufficient for intercourse.ConclusionThis series, to our knowledge, represents the largest cohort of patients who received 2 cryoablation treatments. Local failure after primary cryoablation can be salvaged by second cryosurgery with acceptable intermediate-term disease control. Patients should be counseled regarding the side effect profile associated with second cryoablation.     

联合检测血清HMGB1 PSA在局限性前列腺癌冷冻术后复发中的应用价值

  目的   探讨局限性前列腺癌经前列腺癌氩氦冷冻治疗后血清HMGB1和PSA表达在预测治疗后复发中的临床价值。  方法   应用酶联免疫吸附试验(ELISA) 测定80例局限性前列腺癌患者(Pca组) 冷冻治疗前、后和30例前列腺良性增生患者(BPH组)、20例健康对照者血清HMGB1和PSA表达。Pca组术后PSA、MRI随访, 经病理穿刺活检证实: 局部复发9例, 远处转移3例。比较Pca组术后血清HMGB1表达, 及预测前列腺癌复发的价值。  结果   Pca组术前血清HMGB1 (94.0±77.4 ng/mL) 相比BPH组(33.2±7.4 ng/mL) 和健康对照组(24.7±7.3 ng/mL) 显著升高(P < 0.001)。Pca组术后血清HMGB1 (55.0±11.0 ng/mL) 较术前显著降低(P=0.005);Pca组冷冻治疗后, 复发者术后HMGB1平均值为(70.8±2.7) ng/mL, 无复发者术后HMGB1平均值为(55.0±10.8) ng/mL, 差异有统计学意义(P=0.001);3例远处转移患者血清HMGB1水平较9例局部复发者显著升高(94.2±17.9 vs.73.1±7.9ng/mL)。术后血清HMGB1相比PSA预测复发性Pca的敏感性高(83.3%Vs.66.7%), 而两者联合诊断的特异性较单一PSA高(95.6%vs.82.4%)。Pca组术后HMGB1表达与临床分期、复发和转移(P < 0.001) 相关, 与Gleason评分无显著相关性(P > 0.05)。  结论   血清HMGB1在Pca中高表达, 提示血清HMGB1可作为一项预测和预后指标。此外, Pca患者冷冻治疗后联合检测HMGB1和PSA对于复发患者可提高早期诊断率, 有效的指导病理穿刺活检及后续治疗。      

Early Prostate-Specific Antigen Kinetics for Low- and Intermediate-Risk Prostate Cancer Treated With Definitive Radiation Therapy

PurposeThis study used a patient-specific model to characterize and compare ideal prostate-specific antigen (PSA) kinetics for low- and intermediate-risk prostate cancer after definitive radiation treatment with conventionally fractionated, hypofractionated, stereotactic body radiation therapy, or brachytherapy, both high-dose and low-dose rate.Methods and MaterialsThis retrospective analysis includes low- and intermediate-risk patients with prostate cancer treated between 1998 and 2018 at an National Cancer Institute–designated comprehensive cancer center. Demographics and treatment characteristics were prospectively collected. Patients had at least 2 PSA measurements within 24 months of treatment and were free from biochemical recurrence. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed at 24 months after radiation therapy. Ideal PSA kinetics were characterized for each modality and compared.ResultsOf 1042 patients, 45% had low-risk cancer, 37% favorable intermediate risk, and 19% unfavorable intermediate risk. nPSAs were higher for ablative modalities, both as absolute nPSA and relative to initial PSA. Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% treated with nonablative therapy (conventionally fractionated, hypofractionated, and low-dose rate) reached an nPSA threshold of ≤0.5 ng/mL compared with 23% of stereotactic body radiation therapy and 33% of high-dose rate cohorts. The incidence of bPSA was 13.3% and not affected by treatment modality, Gleason score, or prostate volume. PSA decay rate was faster for ablative therapies in the 6- to 24-month period.ConclusionsAnalysis of PSA within 24 months after radiation therapy revealed ablative therapies are associated with a latent PSA response and higher nPSA. Multivariable logistics modeling revealed younger age, initial PSA above the median, presence of bPSA, and ablative therapy as predictors for not achieving nPSA ≤0.5 ng/mL. PSA decay rate appears to be faster in ablative therapies after a latent period. Understanding the different PSA kinetic profiles is necessary to assess treatment response and survey for disease recurrence.     

Retrospective Analysis of Clinical Outcomes of Stereotactic Body Radiation Therapy for Localized Prostate Cancer at an Asian Cancer Specialist Centre

Introduction: The current treatment options for localized prostate cancer are radical prostatectomy and external beam radiotherapy (EBRT) with stereotactic body radiation therapy (SBRT) gaining interest as a treatment option compared to standard fractionation radiation therapy. This present study is a retrospective study evaluating the correlations between the biochemical efficacy, and treatment toxicity in SBRT for localized prostate cancer. Methods: All organ-confined prostate cancer patients treated with SBRT from 2010 to 2018, at Beacon Hospital, Malaysia were included in this study. Patient demographics, dosimetric parameters, and disease information were retrospectively collected. The primary endpoint was biochemical recurrence-free survival assessed using the Phoenix definition (Nadir + 2 ng/mL). Toxicity outcomes were scored using the Radiation Therapy Oncology Group scale. Results: Fourty-nine patients who met the inclusion criteria (5 low-, 13 intermediate- and 31 high-risk according to the D’amico Risk Classification) received SBRT. The most common dose regime was 34-35Gy in 5 fractions (n=18). Other dose regimes were 24Gy in 3 fractions and 25-33Gy in 5 fractions. Median follow-up was 45.4 months. The median pre-treatment prostate-specific antigen (PSA) was 11.22 ng/mL, which decreased to a median PSA of 0.1 ng/mL by 2 years post-treatment. Out of the 49 cases, only 1 case of biochemical recurrence occurred, yielding a 3- and 5-year overall survival of 100%, and a 3- and 5- year biochemical recurrence-free rate of 100% and 95.2%. Acute grade III urinary toxicities occurred in 1 (2%); whereas acute grade I urinary and rectal toxicities were seen in 22 (44.9%) and 7 (14.3%) patients respectively. Grade I and grade III late rectal toxicities occurred in 3 and 1 patients respectively, while 3 and 1 patient reported late grade I and III urethral stricture respectively. Conclusion: SBRT for clinically-localized and locally advanced prostate cancer provided promising outcomes with low toxicity and good biochemical control.     

Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials

AimsWe conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time–dose–fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored.Materials and methodsThe study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis.ResultsIn total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26–0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04–0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09–0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08–1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28–11.07) with BFFS.ConclusionThe incidence of PSA bounce was independent of time–dose–fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.     

Stereotactic body radiotherapy for localized prostate cancer: Pooled analysis from a multi-institutional consortium of prospective phase II trials

Purpose

The effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested.

Methods and materials

A total of 1100 patients with clinically localized prostate cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003–11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25 Gy in 4–5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2 ng/ml above nadir was analyzed with the Kaplan Meier method.

Results

With a median follow-up of 36 months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ?6, 7 and ?8, respectively (p = 0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively (p < 0.001). No differences were observed with ADT (p = 0.71) or as a function of total dose (p = 0.17). A PSA bounce of >0.2 ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5 years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively.

Conclusion

PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients.     

Oncological and functional results of robotic salvage radical prostatectomy after permanent brachytherapy implants

Purpose

To evaluate the feasibility of robotic salvage prostatectomy for local recurrence after permanent brachytherapy implants for prostate cancer.

Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis

AimsThere is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure.Materials and methodsIndividual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42–54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan–Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases.ResultsSix hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9–7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5–31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1–311.6, P = 0.003).Conclusion4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.     

Neoadjuvant Hormone Therapy for Radical Prostate Radiotherapy: Bicalutamide Monotherapy vs. Luteinizing Hormone-Releasing Hormone Agonist Monotherapy: A Single-Institution Matched-Pair Analysis

BackgroundThe purpose of this study was to compare the prostate-specific antigen (PSA) response to either neoadjuvant bicalutamide (BC) monotherapy or neoadjuvant luteinizing hormone–releasing hormone agonist (LHRHa) monotherapy and the subsequent effect on biochemical failure–free survival (BFFS) in men receiving radical radiotherapy (RT) for localized prostate cancer.Patients and MethodsThis was a retrospective review of consecutive men treated with BC monotherapy before radical prostate RT who were individually case-matched to men treated with neoadjuvant LHRHa monotherapy. PSA kinetics and absolute pre-RT posthormone PSA (PRPH-PSA) level and subsequent BFFS were analyzed.ResultsSixty-five men treated with BC monotherapy with a median follow-up of 44 months were individually matched with 65 men treated with LHRHa with a median follow-up of 54 months. Statistically significant differences were noted between groups in the PRPH-PSA, with a mean of 2.9 ng/mL (0.1-11.2 ng/mL) for patients receiving BC treatment and 1.8 ng/mL (0.1-11.1 ng/mL) for patients receiving LHRHa treatment (P < .001). A PRPH-PSA of < 1.0 and < 0.1 ng/mL was seen in 16 (24.6%) and 2 (3%) of the patients receiving BC and 34 (52.3%) and 3 (4.6%) patients receiving LHRHa, respectively. There were no significant differences between groups in either PSA halving time or velocity. Phoenix biochemical failure occurred in 10 (15.4%) and 8 (12.3%) patients receiving BC and patients receiving LHRHa, respectively. Neither PRPH-PSA level nor PSA kinetics during the neoadjuvant period predict for subsequent BFFS at this duration of follow-up.ConclusionsAlthough neoadjuvant BC therapy did not result in equivalent PRPH-PSA suppression when compared with neoadjuvant LHRHa alone, there was no difference in biochemical failure rates between cohorts at 50 months' median follow-up. Longer follow-up is required.     

Pattern of Recurrence After Stereotactic Radiotherapy in Prostate Cancer Patients With Nodal Pelvic Relapse. A Multi-Institutional Retrospective Analysis

AimsCurrently, when nodal pelvic oligorecurrent disease is detected, no standard treatment option is recommended. One possible salvage option is nodal stereotactic body radiotherapy (SBRT). Here we analysed recurrence patterns after nodal SBRT in patients affected by pelvic oligometastatic relapse after radical prostatectomy, and androgen deprivation therapy (ADT)-free survival in this population.Materials and methodsData on 93 patients consecutively treated in five different institutions for pelvic oligorecurrent disease were reviewed. Inclusion criteria were biochemical recurrence after radical prostatectomy and imaging showing three or fewer metachronous lymphoadenopathies under aortic bifurcation. Patients underwent SBRT on all sites of disease. Concomitant ADT was allowed.ResultsAfter a median follow-up of 20 months (interquartile range 11–41), 57 patients had post-SBRT radiological evidence of relapse, for a median disease-free survival (DFS) of 15 months (95% confidence interval 9–24). Concomitant ADT was administered in 20 patients (21.5%). Overall, eight (8.6%), 21 (22.6%) and 28 (30.1%) patients had prostate bed only, pelvic nodal or distant relapse, respectively. The median ADT-free survival was not reached. Concomitant ADT, International Society for Urologic Pathology pattern at diagnosis < or ≥3, time to relapse ≤ or >12 months, prostate-specific antigen at recurrence < or ≥1.10 ng/ml and prostate-specific membrane antigen staging were not significantly associated with DFS. After relapse, 42 patients (45.2%) received a second SBRT course.ConclusionNodal SBRT yielded encouraging DFS and ADT-free survival in this population. Only a minority of patients developed prostate bed recurrence, suggesting that local treatment may be safely avoided. A consistent percentage of patients could be managed with a second SBRT course.     

Characterizing Prostate-Specific Antigen Levels at Death in Patients with Metastatic Castration-Resistant Prostate Cancer: Are We Underutilizing Imaging?

BackgroundProstate-specific antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer; however, the significance of PSA at or near the time of death is not well understood. This study aimed to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC).Patients and MethodsThe Mount Sinai Genitourinary Cancer Biorepository, an institutional review board–approved, single-institution database containing all consented genitourinary cancer patients seen between 2010 and 2018, was used to identify and stratify patients into the following cohorts based on their PSA at or near death: <100 ng/mL, 100–1000 ng/mL, and >1000 ng/mL. Analyses were performed to assess clinical characteristics of disease, treatment response, and outcomes.ResultsWe identified 1097 patients with prostate cancer, and 101 were confirmed to be deceased following a diagnosis of mCRPC. In patients with mCRPC, cohorts of higher PSA level at death were associated with lower Gleason score at diagnosis and a trend toward longer time to mCRPC and longer time from diagnosis to death, despite a higher burden of disease at death. Conversely, subgroup analysis of PSA < 10 ng/mL at death was associated with lower rates of imaging within 6 months of death, lower treatment rate, and worse clinical outcomes.ConclusionsCohorts of different PSA levels at death in mCRPC patients showed distinct patterns of disease characteristics and clinical outcomes, likely due to the underlying molecular phenotype differences. Imaging for the patient population with very low PSA levels may be underutilized and should be considered more routinely.