Pretreatment Prostate-specific Antigen Research Articles

Outcomes for Patients with Metastatic Castration-Resistant Prostate Cancer and Liver Metastasis Receiving [177Lu]Lu-PSMA-617.

It is well known that patients with liver metastasis from metastatic castration-resistant prostate cancer have poor or only transient responses to many forms of systemic therapy. Data on outcomes after treatment with [177Lu]Lu-PSMA-617 (LuPSMA) are scarce. The VISION trial reports a hazard ratio for overall survival (OS) in the subgroup of patients with liver metastasis without disclosing the absolute duration of survival. Using real-world clinical data, we examined this important subgroup of patients, describing prostate-specific antigen (PSA) response and OS. Methods: A single-institution database was assembled to include all patients receiving LuPSMA at Mayo Clinic in Rochester, Minnesota, for whom treatment was initiated between March 2022 and March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were then categorized by presence or absence of liver metastasis on pretreatment prostate-specific membrane antigen (PSMA) PET. PSA response and OS for the 2 groups (liver metastasis vs. no liver metastasis) were compared using χ2 testing and the Kaplan-Meier method, respectively. A multivariate Cox regression analysis was performed, including established prognostic factors. Finally, those with pretreatment circulating tumor DNA as determined in an 83-gene panel were assessed for the presence of pathogenic and likely pathogenic alterations. These findings were summarized using descriptive statistics and compared between the 2 cohorts using the Fisher exact test. Results: The overall cohort consisted of 273 patients, including 43 (15.75%) with liver metastasis on pretreatment PSMA PET/CT. The median number of cycles received was 3 (range, 1-6) for patients with liver metastasis and 5 (range, 1-6) for those without hepatic involvement. The 50% or greater reduction in PSA from baseline response rate was lower for those with liver metastasis than for those without (30.23% [13/43] vs 49.77% [106/213], P = 0.019). At a median follow-up of 10 mo (interquartile range, 9-13 mo), there was a significant difference in median OS (8.35 mo vs. not reached, P < 0.001). On multivariate analysis, the presence of liver metastasis was independently associated with shorter survival (hazard ratio, 4.06; P < 0.001). Conclusion: Our data suggest that the presence of liver metastasis predicts poorer outcomes in patients receiving LuPSMA treatment. Alternative and combination approaches should be explored to maximize the antitumor activity of radiopharmaceutical therapy in the liver.

Prospective Evaluation of Supplemental External Beam Radiation Therapy With Palladium-103 Prostate Brachytherapy: Long-Term Results of the 44/20/0 Trials

PurposeThe 44/20 and 20/0 randomized trials evaluated whether different external beam radiation therapy (EBRT) dosing regimens prior to brachytherapy impacted biochemical failure (BF). We report long-term outcomes of both trials, and evaluate whether biological equivalent dose (BED) was associated with reduced BF in the combined trial cohort. Materials/methodsBoth trials enrolled patients with clinical T1c-T2b, Gleason score 7-9 and/or a pre-treatment prostate-specific antigen (PSA) 10-20 ng/ml disease. The 44/20 trial randomized patients to 44Gy EBRT with 90Gy palladium (Pd)-103 versus 20Gy EBRT with 115Gy Pd-103. The subsequent 20/0 trial randomized patients to the 20Gy arm versus monotherapeutic 125Gy Pd-103. For each trial, univariate Fine-Gray analysis evaluated whether treatment arm was associated with BF for the entire cohort and the unfavorable intermediate risk (UIR) subgroup. For the combined trial cohort, multivariate Fine-Gray analysis evaluated whether BED was associated with BF, while adjusting for clinical factors. ResultsThere were 247 analyzable patients in the 44/20 trial. At a median follow-up of 13.7 years, there were no differences in BF for the entire cohort (sub-distribution hazard ratio (sHR) 0.99; 95% CI: 0.43, 2.276; p = 0.97) or the UIR subgroup (sHR 0.72; 95% CI: 0.25, 2.08; p = 0.55). There were 383 analyzable patients in the 20/0 trial. At a median follow-up of 10.4 years, there were no differences in BF for the entire cohort (sHR 0.42; 95% CI: 0.13-1.80; p = 0.15) or the UIR subgroup (sHR 0.81; 95% CI: 0.16-4.03; p = 0.80). For the combined cohort (630 patients), BED was not associated with BF (1.00; 95% CI: 0.98-1.02; p = 0.88) on multivariate analyses, while adjusting for androgen deprivation therapy utilization, 4-tiered National Comprehensive Cancer Network category, and year of treatment. ConclusionsBrachytherapy monotherapy should be a standard-of-care treatment for clinically localized, intermediate risk prostate cancer, including UIR disease.

Physician reported toxicities and patient reported quality of life of transperineal ultrasound-guided radiotherapy of prostate cancer

PurposeThis study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). MethodsAcute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. ResultsIn this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8–169 ng/ml). At the median follow-up of 19 months (3–82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. ConclusionThe outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Pretreatment prostate-specific antigen density as a predictor of biochemical recurrence in patients with prostate cancer: a meta-analysis

BackgroundA consensus has not been reached on the value of prostate-specific antigen density (PSAD) as a predictor of biochemical recurrence of prostate cancer. This meta-analysis aimed to evaluate the association between PSAD and biochemical recurrence of prostate cancer after primary treatment.MethodsTwo authors systematically searched PubMed, Web of Science, and Embase databases (up to August September 10, 2023) to identify studies that assessed the value of pretreatment PSAD in predicting biochemical recurrence after primary treatment (radical prostatectomy or radiotherapy) of prostate cancer. A random effect model was used to pool adjusted hazard ratios (HR) with 95% confidence intervals (CI) for biochemical recurrence.ResultsNine studies with 4963 patients were eligible for the meta-analysis. The reported prevalence of biochemical recurrence ranged from 4 to 55.1%. For patients with higher PSAD compared to those with low PSAD, the pooled HR of biochemical recurrence was 1.59 (95% CI 1.21–2.10). Subgroup analysis showed that the pooled HR of biochemical recurrence was 1.80 (95% CI 1.34–2.42) for patients who received radical prostatectomy, and 0.98 (95% CI 0.66–1.45) for patients who received radiotherapy.ConclusionsElevated pretreatment PSAD may be an independent predictor for biochemical recurrence of prostate cancer after radical prostatectomy. Determining PSAD could potentially improve the prediction of biochemical recurrence in patients with prostate cancer.

Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

Enzalutamide, docetaxel and androgen deprivation (ENZADA trial) for metastatic castrate sensitive prostate cancer (mCSPC).

5072 Background: The use of contemporary androgen receptor signaling inhibitors (ARSI) in combination with docetaxel (Doc) and androgen deprivation therapy (ADT) has shown improved outcomes in recent trials. Prostate specific antigen (PSA) serologic complete response (CR) has correlated with improved overall survival (OS) in prior studies. In the E3805 study, the 12-month PSA CR rate was 28% for the ADT + Doc arm. In this study, we hypothesized the combination of androgen deprivation therapy with Doc and enzalutamide (Enz) would improve the 52-week PSA CR rate compared to the historical control with ADT + Doc in newly diagnosed patients with mCSPC. Methods: The ENZADA trial is a single institution phase II study in patients with mCSPC. Patients received ADT, Doc 75 mg/m2 IV every 3 weeks for up to 6 cycles and Enz 160mg daily until radiographic progression. The primary endpoint was 52-week PSA CR. Secondary endpoints included safety/toxicity, best PSA response, time to castration resistance (TTCR) and overall survival (OS). Patients were stratified by radiographic volume of disease by E3805 criteria. The study was designed with 90% power and 1-sided alpha 0.1 to show an improvement in the 52-week PSA CR from 25% to 45%, with rejection of the null hypothesis if 14 of 39 evaluable subjects achieved a 52-week PSA CR. Results: Between Sep 2017 and Aug 2021, 40 subjects were enrolled, and 36 were evaluable for the primary endpoint. At the data cut-off of 9/2/22, median follow up was 42.6 months. Thirty subjects (75%) had high volume disease, and 32 (80%) subjects presented with de novo metastatic disease. Median age was 64.5 years; 65% (N=26) were identified as White and 35% (N=14) were identified as Black or African American (AA). Median pretreatment PSA was 129.5 ng/ml. 67.5% (27/40) of subjects received six cycles of Doc. 10% (4/40) of subjects had Enz dose modifications. 52-week PSA CR occurred in 22/36 (61.1%) patients (P&lt;0.001). 13/23 (56.5%) White subjects and 9/13 (69.2%) Black or African American subjects experienced 52-week PSA CR (P=.50). Median TTCR was not reached; castrate resistance at 2 and 4 years was 62.4% and 53.5%, respectively. Eleven deaths occurred (3/14 Black or AA and 8/26 White); median OS was not reached. OS at 2 and 4 years was 83.2% and 63.1%, respectively. OS at 2 and 4 years was 85.7% and 78.6%, respectively, in Black or AA subjects and 82.4% and 50.9%, respectively, in White subjects (P=.26). Treatment-related Grade 3-5 adverse events occurred in 17/40 (42.5%) patients, including 3 episodes of febrile neutropenia. Conclusions: ADT+Doc+Enz improved 52-week PSA CR compared to historical control with ADT+Doc. These results are consistent with the recent ARASENS and PEACE1 studies and support the use of triplicate regimens combining ADT+Doc+ARSI in newly diagnosed mCSPC patients. No detectable difference in outcome by race has been observed to date in the study cohort. Clinical trial information: NCT03246347 .

The impact of the apparent diffusion coefficient for the early prediction of the treatment response after definitive radiotherapy in prostate cancer patients

PurposeWe assessed early changes in apparent diffusion coefficient (ADC) and serum prostate specific antigen (PSA) values after definitive radiotherapy (RT) without androgen deprivation treatment in low- and intermediate-risk prostate cancer (PC) patients. Materials and MethodsThe clinical data and ADC parameters of 229 PC patients were retrospectively evaluated. Pre-treatment and post-treatment serum PSA and primary tumor ADC values were calculated. Post-treatment DW-MRI was performed median 4.1 months after completion of definitive RT. The prognostic factors predicting freedom from biochemical failure (FFBF) and progression-free survival (PFS) were analyzed using univariable and multivariable analyses. ResultsWith a median follow-up time of 80.8 months, the 5-year FFBF and PFS rates were 95.9% and 89.3%, respectively. Eleven patients (4.8%) had PSA relapse, with a median of 34.4 months after the completion of RT. A statistically significant difference in post-treatment ADC values was noted between patients with and without recurrence (0.94 ± 0.07 vs. 1.10 ± 0.20 × 10-3 mm2/sec; p< 0.001). Patients with a Gleason score (GS) of 6 and low-risk disease had significantly higher post-treatment tumor ADC and PSA levels than patients with a GS of 7 and intermediate-risk disease. The 5-year FFBF rate in patients with tumor ADC ≤ 0.96 × 10-3 mm2/sec was significantly lower than patients with tumor ADC > 0.96 × 10-3 mm2/sec (85.5% vs. 100; p< 0.001). In the multivariable analysis, a lower ADC value, GS 4 + 3 and intermediate-risk disease were independent predictors of worse FFBF. In the multivariate analysis, a lower post-treatment ADC value and a GS of 4 + 3 were significant prognostic factors for a lower PFS. ConclusionThese findings suggest that the post-treatment tumor ADC value could be used for early treatment response evaluation after definitive RT in PC patients.

Proton therapy for high-risk prostate cancer: Results from the Proton Collaborative Group PCG 001-09 prospective registry trial.

Data for proton therapy in high-risk prostate cancer (HRPC) are limited. Using the Proton Collaborative Group prospective registry, we evaluated outcomes for HRPC patients treated with proton therapy. A totsl of 605 men with localized HRPC treated with proton therapy from 8/2009 to 3/2019 at nine institutions were selected. Outcomes examined included freedom from progression (FFP), metastasis free survival (MFS), overall survival (OS), and toxicity. Multivariable cox/binomial regression models were used to assess predictors of FFP and toxicity. Median age was 71 years. Gleason grade groups 4 (49.4%) and 5 (31.7%) were most common, as were clinical stage T1c (46.1%) and cT2 (41.3%). The median pretreatment prostate specific antigen (PSA) was 9.18 and median International Prostate Symptom Score (IPSS) was 6. Androgen deprivation therapy was given in 63.6%. Median dose was 79.2 GyE in 44 fractions. Pelvic lymph nodes were treated in 58.2% of cases. Pencil beam scanning was used in 54.5%, uniform scanning in 38.8%, and a rectal spacer in 14.2%. At a median followup of 22 months, the 3- and 5-year FFP were 90.7% and 81.4%, respectively. Five-year MFS and OS were 92.8% and 95.9%, respectively. Independent correlates of FFP included Gleason ≥8, PSA > 10, and cT2 (all p < 0.05). No grade 4 or 5 adverse events were reported. There were 23 (5%) grade 2 and 0 grade 3 gastrointestinal events. Prevalence of late grade 3, late grade 2, acute grade 3, and acute grade 2 genitourinary toxicity was 1.7%, 5.8%, 0%, and 21.8%, respectively. Prevalence of grade 2 and 3 erectile dysfunction at 2 years was 48.4% and 8.4%, respectively. In the largest series published to date, our results suggest early outcomes using proton therapy for HRPC are encouraging for both safety and efficacy. Further evaluation is needed to determine if an advantage exists to use protons over other radiation techniques in this population.

Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer

BackgroundProstate cancer is one of the most common cancers in men with notable interpatient heterogeneity. Implications of the immune microenvironment in predicting the biochemical recurrence-free survival (BCRFS) after radical prostatectomy and the efficacy of systemic therapies in prostate cancer remain ambiguous.MethodsThe tumor immune contexture score (TICS) involving eight immune contexture-related signatures was developed using seven cohorts of 1120 patients treated with radical prostatectomy (training: GSE46602, GSE54460, GSE70769, and GSE94767; validation: GSE70768, DKFZ2018, and TCGA). The association between the TICS and treatment efficacy was investigated in GSE111177 (androgen deprivation therapy [ADT]) and EGAS00001004050 (ipilimumab).ResultsA high TICS was associated with prolonged BCRFS after radical prostatectomy in the training (HR = 0.32, 95% CI 0.24–0.45, P < 0.001) and the validation cohorts (HR = 0.45, 95% CI 0.32–0.62, P < 0.001). The TICS showed stable prognostic power independent of tumor stage, surgical margin, pre-treatment prostatic specific antigen (PSA), and Gleason score (multivariable HR = 0.50, 95% CI 0.39–0.63, P < 0.001). Adding the TICS into the prognostic model constructed using clinicopathological features significantly improved its 1/2/3/4/5-year area under curve (P < 0.05). A low TICS was associated with high homologous recombination deficiency scores, abnormally activated pathways concerning DNA replication, cell cycle, steroid hormone biosynthesis, and drug metabolism, and fewer tumor-infiltrating immune cells (P < 0.05). The patients with a high TICS had favorable BCRFS with ADT (HR = 0.25, 95% CI 0.06–0.99, P = 0.034) or ipilimumab monotherapy (HR = 0.23, 95% CI 0.06–0.81, P = 0.012).ConclusionsOur study delineates the associations of tumor immune contexture with molecular features, recurrence after radical prostatectomy, and the efficacy of ADT and immunotherapy. The TICS may improve the existing risk stratification systems and serve as a patient-selection tool for ADT and immunotherapy in prostate cancer.

Oncological outcomes with wide resection in robot-assisted radical prostatectomy as primary treatment for very high-risk prostate cancer.

357 Background: Patients with very high-risk prostate cancer (VHRPCa) have earlier biochemical recurrences (BCRs) and higher mortality rates. It remains unclear whether extended robot-assisted radical prostatectomy (eRARP) with intended wide resection can improve the outcomes of VHRPCa patients. We aimed to compare the oncological outcomes of eRARP versus standard RALP (sRARP) for primary treatment of VHRPCa. Methods: We retrospectively evaluated 168 patients classified by the National Comprehensive Cancer Network (NCCN) as very high-risk who were treated with RARP without neoadjuvant/adjuvant therapy between September 2011 and December 2020. eRARP was performed using the extra-fascial approach as reported by Gandaglia G et al. (Eur Urol. 71:249-256, 2017). We performed 1:1 propensity score matching to account for potential differences between eRARP and sRARP. Kaplan-Meier analysis and Cox regression models were used to test the effect of eRARP on the biochemical progression-free survival (bPFS). This observational study was approved by the Institutional Review Board. Results: There were 93 patients in the eRARP group and 75 in the sRARP group. The eRARP group had a worse clinical stage than the sRARP group ( p&lt; 0.001). Age, pretreatment prostate specific antigen (PSA), and pretreatment Gleason score were similar in the two groups. All patients in the eRARP group underwent pelvic lymph node dissection, compared with 89% in the sRARP group. The propensity-adjusted 3-year biochemical recurrence-free survival rates was 31.4% in the sRARP group and 67.4% in the eRARP group(p=0.001), respectively. The adjusted Cox regression analysis showed that the eRARP group had a significantly longer bPFS than the sRARP group (hazard ratio 0.415, p=0.0047). Conclusions: In patients with VHRPCa, eRARP was associated with a reduce risk of biochemical recurrence. These results suggest that eRARP may improve oncological outcomes in VHRPCa.

Circulating tumor DNA and homologous recombination deficiency in bone-predominant mCRPC prior to radium-223 therapy.

203 Background: Radium-223 (Ra-223) is a bone-seeking alpha emitter that induces double-stranded DNA breaks, and the homologous recombination (HR) pathway is critical for repairing these breaks. While prior studies suggested that metastatic castrate-resistant prostate cancers (mCRPC) patients (pts) with HR-deficient (HRD+) tumors may be more likely to benefit from Ra-223, obtaining tissue for next generation sequencing to identify HRD+ is challenging in pts with bone-predominant disease. We hypothesized that circulating tumor DNA (ctDNA) would allow for broader identification of HRD+ to assess association with clinical outcomes in a real-world cohort. Methods: We identified 135 mCRPC pts treated with Ra-223 at our institution between 2013 and 2021. Pts who initiated another anti-tumor therapy within 60 days of Ra-223 treatment were excluded; pts continuing hormonal agents initiated &gt;60 days prior were included. ctDNA isolated from pre-treatment plasma underwent ultra-low-pass whole genome sequencing to estimate tumor fraction (TF). Additionally, targeted panel sequencing using an institutional prostate cancer-specific panel of 319 genes with duplex sequencing (utilizing unique molecular identifiers) for error suppression was used to identify germline or somatic deleterious alterations in HR pathway genes. The primary outcome was association between HRD status and completion of fewer than 6 cycles (as a proxy for early clinical progression), assessed using logistic regression. Results: The median age was 61 (IQR, 56-67) years, median pretreatment prostate-specific antigen (PSA) level was 26.2 (IQR, 8.1-84.1) ng/mL, and median TF was 4% (IQR, 3-6%). 97% of pts (n=131) previously received a novel antiandrogen, and 63% (n=85) received prior taxane. 17% (n=23) were HRD+, and 59% (n=80) completed 6 cycles of Ra-223. On multivariable analysis, HRD+ was associated with decreased likelihood of completing 6 cycles compared to HRD- (adjusted odds ratio [AOR] 0.16, 95% confidence interval [CI] 0.05-0.48, P=0.001). 22% (n=5) of HRD+ pts completed 6 cycles compared to 67% (n=75) of HRD- pts. Additional factors associated with decreased likelihood of completing 6 cycles included a higher pretreatment TF (AOR 0.69, 95% CI, 0.48-0.97, P=0.034) and prior taxane use (AOR 0.41, 95% CI, 0.18-0.91, P=0.028), but not pretreatment PSA ( P=0.574). Conclusions: Targeted panel sequencing with error suppression from ctDNA identified HRD+ in mCRPC pts with bone-predominant disease and low median TF at a similar frequency as reported from tissue. In our cohort, HRD+ was prognostic of early clinical progression with Ra-223. Further work is in progress to understand the association of other ctDNA-derived features, including assessment of genomic signatures and transcriptional binding sites, in the setting of Ra-223 therapy. DF/HCC IRB protocol 18-135.

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

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. 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. 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. SBRT for clinically-localized and locally advanced prostate cancer provided promising outcomes with low toxicity and good biochemical control.

Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy

AimsTo report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. Materials and methodsIn 2003–2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan–Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. ResultsOf 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3–7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. ConclusionIn low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.

Comparative evaluation of hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate and high risk prostate cancer.

The purpose of this study was to comparatively evaluate an efficacy and toxicity profile of hypofractionated radiotherapy (67.5 Gy in 25 fractions) to conventionally fractionated radiotherapy (78 Gy in 39 fractions) in prostate cancer patients with intermediate and high-risk disease. From January 2015 to December 2018, 168 patients were randomized to hypofractionated radiation treatment and conventional fractionated radiation treatment schedules of volumetric modulated arc therapy (VMAT) to the prostate and seminal vesicles. All the patients also received androgen deprivation therapy (ADT) and radiation therapy started after ADT. The median (range) follow-up was 51 (31-63) and 53 (33-64) months in the hypofractionated and conventionally fractionated regimes, respectively. The 3-year biochemical no evidence of disease (bNED) rates were 86.9% and 73.8% in the hypofractionated and conventionally fractionated groups, respectively (p = 0.032, significant). The 3-year bNED rates in patients at a high risk [i.e., pretreatment prostate-specific antigen (PSA) > 20 ng/mL, Gleason score ≥ 8, or T ≥ 2 c], were 87.9% and 73.5% (p = 0.007, significant) in the hypofractionated and conventionally fractionated radiotherapy groups, respectively. No statistically significant difference was found for late toxicity between the two groups, with 3-year grade 2 gastrointestinal toxicity rates of 19% and 16.7% and 3-year grade 2 genitourinary toxicity rates of 15.5% and 11.9% in the hypofractionated and conventionally fractionated radiotherapy groups, respectively. Hypofractionated schedule is superior to the conventional fractionation schedule of radiation treatment in terms of bNED in intermediate and high grade prostate cancer patients. Also, the late toxicity is found to be equivalent between the two treatment groups.

18F-PSMA-1007 PET/CT-derived semi-quantitative parameters for risk stratification of newly diagnosed prostate cancer.

This study aimed to assess the value of 18F-PSMA-1007 positron emission tomography/computed tomography (PET/CT)-derived semi-quantitative parameters of primary tumor for risk stratification of newly diagnosed prostate cancer (PCa). Sixty patients referred for 18F-PSMA-1007 PET/CT imaging for primary PCa were retrospectively analyzed and classified into the low-intermediate-risk (LIR) or high-risk (HR) group. The maximum standardized uptake value (SUVmax) of primary tumor, prostate total lesion PSMA (TL-PSMAp), and prostate PSMA-tumor volume (PSMA-TVp) were measured, and group differences were evaluated using the Mann-Whitney U test. Spearman's correlation was performed to assess the correlation between the above parameters with prostate-specific antigen (PSA) levels and Gleason score (GS). Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for SUVmax, TL-PSMAp, and PSMA-TVp to identify high-risk PCa and compare diagnostic efficacy. Among 60 patients, 46 were assigned to the HR group and 16 to the LIR group. In all patients, SUVmax, TL-PSMAp, and PSMA-TVp were moderately correlated with pre-treatment PSA values (r = 0.411, p = 0.001; r = 0.663, p < 0.001; and r = 0.549, p < 0.001, respectively). SUVmax and TL-PSMAp were moderately correlated with GS (r = 0.457 and r = 0.448, respectively; p < 0.001), while PSMA-TVp was weakly correlated with GS (r = 0.285, p = 0.027). In the ROC curve analysis, the optimal cut-off values of SUVmax, TL-PSMAp, and PSMA-TVp for identifying high-risk PCa were 9.61, 59.62, and 10.27, respectively, and the areas under the operating curve were 0.828, 0.901, and 0.809, respectively. The sensitivities of SUVmax, TL-PSMAp, and PSMA-TVp were 91.03%, 71.74%, and 63.04%, respectively, and the specificities were 71.43%, 100.00%, and 92.86%, respectively. TL-PSMAp had a superior ability to identify high-risk PCa. The semi-quantitative parameters of primary tumor on 18F-PSMA-1007 PET/CT imaging can be an objective imaging reference index to determine PCa risk stratification.

Conditional Survival Probabilities in Recurrent Prostate Cancer (PCa) Patients Receiving Radiation ± Antiandrogen Therapy: Secondary Analysis of a Randomized Clinical Trial

<h3>Purpose/Objective(s)</h3> Salvage radiation therapy (SRT) and androgen-deprivation therapy (ADT) are routinely used in patients with elevated prostate-specific antigen (PSA) levels after radical prostatectomy (RP). Although overall survival (OS) and biochemical-failure (BF) following SRT are useful when counseling patients at the time of treatment, the utility of survival data from time of diagnosis diminishes over time. Conditional survival (CS) can provide more relevant estimates, especially given long-term PCa survivorship. The primary aim of this study was to analyze CS estimates for recurrent PCa patients undergoing SRT ± ADT. The secondary objective was to determine if factors prognostic of OS and BF at diagnosis remain relevant in survivorship. <h3>Materials/Methods</h3> We analyzed data from 760 post-RP patients enrolled in NRG/RTOG 9601 (1998–2003). Eligible patients included men who had undergone prior RP and had pT2/T3 disease without nodal involvement and detectable PSA levels of 0.2–4.0 ng/mL. Patients were randomly assigned to undergo SRT and receive either 24 mo of ADT or placebo. OS was calculated (Kaplan–Meier), cumulative incidence was used to estimate BF rates, and prognostic factors associated with OS and BF were analyzed by multivariable Cox proportional hazards modeling (MVA). <h3>Results</h3> Patients were followed for a median of 13 y. The 5- and 10-y OS estimates from diagnosis were 93% and 80%, respectively. At 1- (<i>n</i> = 755), 3- (<i>n</i> = 727), 5- (<i>n</i> = 680), 8- (<i>n</i> = 602), and 10-y (<i>n</i> = 543) survivorship, chances of surviving an additional 5 y were 92%, 89%, 86%, 80%, and 72%, respectively. On MVA at diagnosis, omission of ADT (HR 1.308, <i>P</i> = 0.0403), increasing age (HR 2.761, <i>P</i> < 0.0001), and Gleason score (GS) 8−10 (HR 1.054, <i>P</i> =0.01), were associated with all-cause mortality. For those who achieved survivorship at 5 y, only age (HR 2.973, <i>P</i> < 0.0001) and GS 8–10 (HR 1.801, <i>P</i> = 0.0063) were prognostic of mortality on MVA. The 5- and 10-y rates of BF from diagnosis were 36% and 52%, respectively. For patients who survived 1 (<i>n</i> = 725), 3 (<i>n</i> = 560), 5 (<i>n</i> = 435), 8 (<i>n</i> = 320), and 10 (<i>n</i> = 268) y without BF, chances of BF at an additional 5 y were 39%, 33%, 26%, 20%, and 20%, respectively. On MVA at time of SRT, omission of ADT (HR 2.139, <i>P</i> < 0.0001), GS 7 (HR 1.376, <i>P</i> = 0.0062), GS 8–10 (HR 1.717, <i>P</i> = 0.0005), and higher pretreatment PSA (HR 1.442, <i>P</i> = 0.0215), were associated with BF. For those who survived 5 y after treatment without failure, only omission of ADT (HR 1.407, <i>P</i> < 0.0384) was prognostic of BF. <h3>Conclusion</h3> Conditional risk of BF for patients treated with SRT remains elevated at levels similar to those at initial treatment for up to 3 y after SRT, after which BF rates decrease. ADT continues to confer a reduced risk for BF for long-term survivors. This data can be used to inform survivorship care planning and highlights the need for continued PSA surveillance after completion of treatment.

Validation of the Combination Gleason Score as an Independent Favorable Prognostic Factor in Prostate Cancer Treated With Dose-Escalated Radiation Therapy

PurposePrognostic factors for prostate cancer include tumor, node, metastases stage, pretreatment prostate-specific antigen, and pathology (via Gleason score [GS] or grade group). Of these, GS yields the largest effect on prostate cancer specific mortality. It was previously determined that those with cores with a mix of higher and lower GS at biopsy (which was termed a “ComboGS”) had decreased risk for prostate cancer specific mortality after either surgical or radiation treatment. We validate the effect of ComboGS in an independent cohort of patients with prostate cancer treated with definitive dose-escalated radiation therapy (DE-RT) at 2 institutions. Methods and MaterialsDE-RT was administered to 2539 men, of which 687 men had a ComboGS. To further ascertain the ComboGS effect we employed the modified Cancer of the Prostate Risk Assessment (mCAPRA) score. Rates of biochemical event-free survival and distant metastasis-free survival were compared across CAPRA scores, with and without modification, and the prognostic value of the CAPRA scores was compared using Harrel's concordance index. ResultsOn univariate analysis in Gleason 7 to 10 patients the presence of ComboGS improved 10-year biochemical event-free survival from 76.6% to 82.4% (hazard ratio [HR], 0.75; confidence interval [CI], 0.59-0.96; P = .021), 10-year distant metastasis-free survival from 89.3% to 93.2% (HR, 0.57; CI, 0.39-0.85; P = .005), 10-year prostate cancer specific survival from 93.9% to 97.4% (HR, 0.39; CI, 0.21-0.7; P = .001), and 10-year overall survival from 65.7% to 75.6% (HR, 0.69; CI, 0.57-0.83; P < .001). Multivariable analysis also supported that ComboGS is protective for biochemical failure (HR, 0.64; CI, 0.50-0.83; P < .001), distant metastasis (HR, 0.42; CI, 0.28-0.63; P < .001), death from prostate cancer (HR, 0.32; CI, 0.17-0.58; P < .001), and overall mortality (HR, 0.65; CI, 0.54-0.79; P < .001). Additionally, adjusting the mCAPRA score for ComboGS decreased the risk of biochemical failure by nearly 30% (HR, 0.70; 95% CI, 0.55-0.88; P = .003) and by 50% (HR, 0.54; 95% CI, 0.37-0.80; P = .002) for distant metastasis. ConclusionsComboGS is a useful and readily available independent prognostic factor for all clinical endpoints evaluated. Moreover, the ComboGS can be used in conjunction with the extensively validated CAPRA scoring to better risk stratify patients being treated with definitive DE-RT for GS 7 to 10 disease.

Long-term outcomes of radical prostatectomy versus low-dose-rate brachytherapy in patients with intermediate-risk prostate cancer: Propensity score matched comparison.

To compare long-term outcomes of radical prostatectomy (RP) and low-dose-rate brachytherapy (LDR-BT) using propensity score-matched analysis in patients with clinically localized, intermediate-risk prostate cancer (PCa). Between October 2003 and March 2014, our institution treated 1241 patients with intermediate-risk PCa (RP: n = 531; LDR-BT: n = 710). Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) levels of 0.2 ng/ml or greater for RP, and as PSA nadir plus 2 ng/ml or higher (Phoenix definition) for LDR-BT. We calculated propensity scores by multivariate logistic regression based on covariates that included age, pretreatment PSA, biopsy Gleason grade, the percentage of positive biopsy cores (PPBC), and clinical T stage. Median follow-up was 108 months for RP and 99 months for LDR-BT. After propensity score adjustment, a total of 642 (321 each) patients remained for further analysis. Kaplan-Meier curves showed no statistically significant difference in overall survival (OS) (p = 0.99). LDR-BT was associated with improved BCR-free survival and salvage therapy-free survival compared to RP (p < 0.001), and RP was associated with improved metastasis-free survival (MFS, p < 0.001). BCR cannot be a surrogate for survival comparison, primarily due to differences between treatment modalities in how this term was defined post-therapy. Long-term follow-up showed that RP was associated with lower MFS in intermediate-risk PCa. However, this has not yet translated into superior OS.

Role of baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters in predicting survival outcomes of metastatic castration-resistant prostate cancer patients receiving first-line treatment.

We aimed to evaluate whether baseline 68Ga-PSMA PET/CT-derived whole-body volumetric parameters could be used as predictive biomarkers for survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line treatment. This retrospective study included 54 mCRPC patients, who underwent baseline 68Ga-PSMA PET/CT imaging within 1month before starting first-line treatment. Pre-treatment prostate-specific antigen (PSA) levels and treatments were recorded. SUVmax, SUVmean, whole-body PSMA-derived tumor volume (wbPSMA-TV), and whole-body total lesion PSMA (wbTL-PSMA) were calculated for all patients. PSA response was defined as a decline of ≥ 50% from pre-treatment value at 12weeks. Overall survival (OS) was measured from the start of the first-line treatment for mCRPC. Docetaxel and abiraterone/enzalutamide were administered to 32 and 22 patients in the first-line setting, respectively. wbPSMA-TV (rho = 0.582, p = 0.004) and wbTL-PSMA (rho = 0.564, p = 0.007) showed moderate positive correlations with PSA levels. Older age (p = 0.02), higher wbPSMA-TV (p = 0.007), higher PSA (p = 0.01), higher number of bone metastases (p = 0.02), and lack of PSA response (p = 0.03) were significantly associated with an increased risk of mortality. Multivariate analysis determined wbPSMA-TV (HR: 1.003, 95% CI 1.001-1.004, p = 0.001) and PSA response (HR: 2.241, 95% CI 1.189-4.222, p = 0.01) as independent predictors of OS. The wbPSMA-TV may be a useful tool to reflect tumor burden and predict survival outcomes in patients with mCRPC.

Robot-assisted radical prostatectomy in the treatment of patients with clinically high-risk localized and locally advanced prostate cancer: single surgeons functional and oncologic outcomes

BackgroundOptimal treatment approaches for high-risk localized and locally advanced prostate cancer remain controversial and there are currently no standard treatments. These patients with high-risk localized and locally advanced prostate cancer are usually offered radiotherapy in combination with hormonal therapy. We report functional and oncologic outcomes of patients who underwent primary robot-assisted radical prostatectomy (RARP) and assess the role of RARP in patients with high-risk localized and locally advanced prostate cancer.MethodsThis study included 188 patients with high-risk localized (clinical stage T2c or a pretreatment prostate-specific antigen level > 20 ng/mL or a biopsy Gleason score ≥ 8) and/or locally advanced (any PSA, cT3-4 or cN+) prostate cancer who underwent RARP between July 2013 and May 2020. Functional outcomes including postoperative continence and potency were assessed at 1, 3, 6, and 12 months after RARP. Oncologic outcomes comprised positive surgical margins (PSMs), biochemical recurrence (BCR), BCR-free survival, and clinical recurrence (CR)-free survival rates at 1 and 3 years.ResultsThe median operative time was 185 (interquartile range [IQR] 130–260) minutes. Based on postoperative pathology, the rates of PSMs in the entire cohort and in those with stage pT2 disease were 26.6% and 8.5%, respectively. The continence and potency rates at 12 months were 88.3% and 56.4%, respectively. The BCR rate was 22.3%, and the median time to BCR was 10.5 (IQR 3.5–26.9) months. The 1- and 3-year BCR-free survival rates were 87.6% and 78.7%, respectively, and the 1- and 3-year CR-free survival rates were 97.5% and 90.8%, respectively.ConclusionsMost patients with clinically high-risk localized and locally advanced prostate cancer treated with primary RARP remained BCR-free and CR-free during the 1- and 3-year follow-up, demonstrating the good functional outcomes with RARP. RARP was a safe and feasible minimally invasive surgical alternative to radiotherapy or hormonal therapy in select patients with high-risk localized and locally advanced prostate cancer. These results should be validated to assure the reproducibility of measurements in prospective randomized-controlled studies on primary RARP.