Outcomes and Prediction Models for Exclusive Prostate Bed Salvage Radiotherapy among Patients with Biochemical Recurrence after Radical Prostatectomy

Background: The addition of androgen-deprivation therapy (ADT) or pelvic radiation to prostate bed salvage radiotherapy (SRT) has been debated for prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy. This study aimed to assess the outcomes and propose prediction models for exclusive prostate bed SRT. Methods: This is a prospective observational cohort study with patients who underwent SRT with a pre-SRT PSA < 1.5 ng/mL after radical prostatectomy. Patients were treated with 70-Gy SRT to the prostate bed exclusively. Kaplan–Meier survival analyses and Cox regression analyses were applied for depicting and predicting BCR-free survival, ADT-free survival, and metastasis-free survival (MFS). Regression-based coefficients were used to develop nomograms. Results: A total of 105 patients were included and 91 patients were eligible. The median follow-up period was 39 months. The 5-year BCR-free survival, ADT-free survival, and MFS were 37%, 50%, and 66%, respectively. Multivariable analysis showed that a pre-SRT PSA < 0.45 ng/mL was the only independent factor associated with longer BCR-free survival (p = 0.034), while a PSA-DT > 8 months had better ADT-free survival (p = 0.008). Patients with a PSA-DT > 8 months showed a 100% MFS and a 43% 5-year absolute benefit in MFS than a PSA-DT ≤ 8 months. All patients with a pre-SRT PSA < 0.45 ng/mL and PSA-DT > 8 months were free from subsequent ADT and any metastasis. Conclusions: In patients with a PSA < 0.45 ng/mL and PSA-DT > 8 months for post-prostatectomy BCR, prostate bed SRT provided excellent outcomes without the need for concomitant ADT or pelvic radiotherapy.

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Outcome after PSMA-PET/CT-based salvage radiotherapy for nodal recurrence after radical prostatectomy

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05557-z ◽

2021 ◽

Author(s):

Paul Rogowski ◽

Christian Trapp ◽

Rieke von Bestenbostel ◽

Chukwuka Eze ◽

Ute Ganswindt ◽

...

Keyword(s):

Multivariate Analysis ◽

Radical Prostatectomy ◽

Lymph Nodes ◽

Biochemical Recurrence ◽

Local Therapy ◽

Salvage Radiotherapy ◽

Free Survival ◽

Kaplan Meier ◽

Psma Pet ◽

Pet Ct

Abstract Purpose Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. Methods A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method and uni- and multivariate analysis was performed. Results Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1–40.1) in patients with bcP and 1.4 ng/ml (range 0.3–5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60–70 Gy) was delivered to the prostatic fossa, 70 Gy (66–72 Gy) to the local recurrence, if present, 65.1 Gy (56–66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4–50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. Conclusions Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.

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Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy

Frontiers in Oncology ◽

10.3389/fonc.2021.669261 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hind Zaine ◽

Benjamin Vandendorpe ◽

Benoit Bataille ◽

Thomas Lacornerie ◽

Jennifer Wallet ◽

...

Keyword(s):

Radical Prostatectomy ◽

Local Recurrence ◽

Hormone Therapy ◽

Progression Free Survival ◽

Salvage Radiotherapy ◽

Metastatic Progression ◽

Free Survival ◽

Prostate Bed ◽

Concomitant Boost ◽

Biochemical Progression

IntroductionSalvage radiotherapy is the only curative treatment for biochemical progression after radical prostatectomy. Macroscopic recurrence may be found in the prostatic bed. The purpose of our study is to evaluate the effectiveness of salvage radiotherapy of the prostate bed with a boost to the area of the macroscopic recurrence.Material and MethodsFrom January 2005 to January 2020, 89 patients with macroscopic recurrence in the prostatectomy bed were treated with salvage radiotherapy +/- hormone therapy. The average PSA level prior to radiotherapy was 1.1 ng/mL (SD: 1.6). At the time of biochemical progression, 96% of the patients had a MRI that revealed the macroscopic recurrence, and 58% had an additional choline PET scan. 67.4% of the patients got a boost to the macroscopic nodule, while 32.5% of the patients only underwent radiotherapy of the prostate bed without a boost. The median total dose of radiotherapy was 70 Gy (Min.: 60 – Max.: 74). The most commonly-used regimen was radiotherapy of the prostatectomy bed with a concomitant boost. 48% of the patients were concomitantly treated with hormone therapy.ResultsAfter a median follow-up of 53.7 months, 77 patients were alive and 12 had died, of which 4 following metastatic progression. The 5-year and 8-year survival rates (CI95%) are, respectively, 90.2% (78.9-95.6%) and 69.8% (46.4-84.4%). The 5-year biochemical progression-free survival rate (CI95%) is 50.8% (36.7-63.3). Metastatic recurrence occurred in 11.2% of the patients. We did not find any statistically significant impact from the various known prognostic factors for biochemical progression-free survival. No toxicity with a grade of > or = to 3 was found.ConclusionsOur series is one of the largest published to date. Salvage radiotherapy has its place in the management of patients with biochemical progression with local recurrence in the prostate bed, with an acceptable toxicity profile. The interest of the boost is to be evaluated in prospective trials.

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Salvage therapies for radiation-relapsed IDH-mutant astrocytoma and 1p/19q codeleted oligodendroglioma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab081 ◽

2021 ◽

Author(s):

Sirui Ma ◽

Soumon Rudra ◽

Jian L Campian ◽

Milan G Chheda ◽

Tanner M Johanns ◽

...

Keyword(s):

Cox Regression ◽

Salvage Surgery ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Cancer Center ◽

First Line ◽

Free Survival ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Tertiary Cancer Center

Abstract Background Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches. Methods Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or non-alkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis. Results Recurrent Oligo (n=35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, P = 0.002) and OS (median: 6.3 vs 1.5 years, respectively, P < 0.001) than Astro (n=59). Overall, 90% of recurrences were local. Eight-three percent received AC as the first-line SST; 50% received salvage surgery before SST; approximately 50% with local failure >2 years after prior RT received reirradiation. On MVA, non-AC was associated with worse OS for both Oligo and Astro; salvage surgery was associated with improved PFS and OS for Astro; early reirradiation was associated with improved PFS for Astro. Conclusions Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment.

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The Long-Term Outcomes after Radical Prostatectomy of Patients with Pathologic Gleason 8–10 Disease

Advances in Urology ◽

10.1155/2012/428098 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Dan Lewinshtein ◽

Brandon Teng ◽

Ashley Valencia ◽

Robert Gibbons ◽

Christopher R. Porter

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Cox Regression ◽

Surgical Margin ◽

Cancer Control ◽

Positive Surgical Margin ◽

Cancer Specific Survival ◽

Free Survival ◽

Kaplan Meier

Background. We explored the long-term clinical outcomes including metastases-free survival and prostate cancer-specific survival (PCSS) in patients with pathologic Gleason 8–10 disease after radical prostatectomy (RP).Methods. We report on 91 patients with PCSS data with a median followup of 8.2 years after RP performed between 1988 and 1997. Cox regression and Kaplan-Meier analysis were used to evaluate year of surgery, pathologic stage, and surgical margin status as predictors of PCSM.Results. Median age was 65 years (IQR: 61–9), and median PSA was 9.7 ng/ml (IQR: 6.1–13.4). Of all patients, 62 (68.9%) had stage T3 disease or higher, and 48 (52.7%) had a positive surgical margin. On multivariate analysis, none of the predictors were statistically significant. Of all patients, the predicted 10-year BCR-free survival, mets-free survival, and PCSS were 59% (CI: 53%–65%), 88% (CI: 84%–92%), and 94% (CI: 91%–97%), respectively.Conclusions. We have demonstrated that cancer control is durable even 10 years after RP in those with pathologic Gleason 8–10 disease. Although 40% will succumb to BCR, only 6% of patients died of their disease. These results support the use of RP for patients with high-risk localized prostate cancer.

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Redefining postprostatectomy biochemical progression: The significance of a PSA cutoff below 0.2 ng/ml—Results from two retrospective series with and without salvage radiotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.153 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 153-153

Author(s):

Lars Budäus ◽

Jonas Schiffmann ◽

Pierre Tennstedt ◽

Dirk Bottke ◽

Hans Heinzer ◽

...

Keyword(s):

Overall Survival ◽

Cox Regression ◽

Progression Free Survival ◽

Salvage Radiotherapy ◽

Clinical Progression ◽

Free Survival ◽

Kaplan Meier ◽

Psa Progression ◽

Biochemical Progression

153 Background: Biochemical recurrence (BCR) after radical prostatectomy (RP) is usually defined at a PSA >0.2 ng/ml. BCR may precede clinical progression by years. Though salvage radiotherapy (SRT) is recommend to be initiated at PSA <0.5 ng/ml, its efficiency at PSA <0.2 ng/ml is not well documented. Methods: We relied on two independent post-RP cohorts. Cohort 1 (n=311, Hamburg) comprised men whose post-RP PSA levels had risen to 0.1-0.2 ng/ml. Further biochemical and clinical progression were recorded during follow-up. Cohort 2 (n=198, Berlin) were patients with BCR who received SRT (66/72 Gy) at a PSA <0.5 ng/ml. The median follow-up was 6.9 years. Post-SRT progression and overall survival were addressed by Kaplan-Meier analysis and Cox regression modelling. Results: In cohort 1, 299 (96%) men experienced further PSA progression (>0.2 ng/ml) within a median time of 7 months. Subsequent PSA rise to >0.3, >0.4, and >0.6 ng/ml was recorded in 174 (58%), 123 (41%), and 24 (8%) men, respectively. Twenty-four (8%) men developed metastases. In cohort 2, 112 men received SRT at PSA between 0.03 and 0.2 ng/ml, and 86 at 0.2-0.499 ng/ml. The latter group, had a poorer 10-years BCR-free Kaplan-Meier rate, 43% vs. 66% (p=0.051). Together with pT<3, Gleason Score <7, and post-RP PSA <0.03 ng/ml, SRT at PSA <0.2 ng/ml was an independent favorable predictor of freedom from BCR (OR=0.60, p<0.05). Ultimately, 14 patients died. However, overall survival did not significantly correlate with the pre-SRT PSA. Conclusions: The vast majority of patients with a PSA >0.1 ng/ml after RP will subsequently progress to PSA >0.2 ng/ml. Improved progression free survival can be achieved, if SRT is administered at a PSA <0.2 ng/ml. Therefore the contemporary PSA threshold for defining BCR after RP needs to be reconsidered and early sRT should be contemplated on a individual basis for optimizing oncological outcomes.

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Influence of node-positive disease after radical prostatectomy on biochemical recurrence and oncologic outcomes in men with prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.306 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 306-306

Author(s):

Samuel L. Washington ◽

Janet E. Cowan ◽

Annika Herlemann ◽

Kyle Brian Zuniga ◽

Peter Carroll

Keyword(s):

Radical Prostatectomy ◽

Biochemical Recurrence ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Oncologic Outcomes ◽

Secondary Treatment ◽

Recurrence Free Survival ◽

Nodal Disease ◽

Free Survival ◽

Increased Risk

306 Background: The diagnostic and therapeutic value of pelvic lymph node dissection (LND) at radical prostatectomy (RP) remains unclear. Thus, we aim to characterize the oncologic value of LND and secondary treatment on oncologic outcomes for a contemporary cohort of men with nodal disease on surgical pathology at RP. Methods: Men who underwent primary RP with LND for PCa were identified and stratified by pN status. Detectable PSA was defined as a PSA>0.05 ng/ml within 2-6 months after RP. Multivariable Cox proportional hazards regression models were fit for biochemical recurrence-free survival (RFS), overall survival (OS), and PCa-specific mortality (PCSM). Results: Of 1,635 identified patients, 167 (10.2%) had nodal disease. Mean age at diagnosis was 62 years (SD 7.1). Median follow-up after RP was 31 months (IQR 13-58). Those with nodal disease had more extensive LND (mean 17.7, SD 8.3 vs mean 13, SD 7.6, p<0.01). The number of positive LNs was associated with worse 7-year outcomes [RFS, HR 1.2, 95% CI 1.1-1.2, p<0.01; OS, HR 1.2, 95% CI 1.1-1.4, p<0.01] but not PCSM (p=0.2) after adjustments. Median number of positive LN was 1 (IQR 1, 3) in pN1 patients. 31 (19%) had an UDT PSA after RP, 25 (15%) had UDT PSA and received adjuvant therapy, and 106 (66%) had a detectable PSA. On multivariable analysis, number of positive LNs (HR 1.1, 95% CI 1.0-12, p=0.02) and detectable PSA (vs UDT, HR 5.1, 95% CI 1.8-14.3, p<0.01) were associated with increased risk of recurrence after RP but not OS (p>0.05 for all). After salvage treatment, 7-year RFS, OS, and PCSM did not differ significantly between the groups (p>0.05 for all). Conclusions: In a contemporary cohort of men with pN1 disease, more extensive LND was not associated with improved outcomes. Amongst those who underwent secondary treatment after RP, UDT PSA after RP conferred greater biochemical recurrence free survival at 7 years. In this subset of men, adjuvant treatment was not associated with improved post-salvage biochemical or treatment-free survival. Further investigation into the potential therapeutic benefit of LND at RP is warranted to better estimate the potential risk overtreatment of men with nodal disease.

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Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.38 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 38-38

Author(s):

Emma Grace Wright ◽

Amarnath Challapalli ◽

Paul White ◽

Rajendra Persad ◽

Susan Masson ◽

...

Keyword(s):

Radical Prostatectomy ◽

Progression Free Survival ◽

Rank Test ◽

Time Interval ◽

Free Survival ◽

Psa Relapse ◽

Prostate Bed ◽

Kaplan Meier ◽

Significant Difference ◽

Biochemical Progression

38 Predictors of improved biochemical progression free survival for salvage prostate bed radiotherapy after radical prostatectomy Background: About a third of patients undergoing radical prostatectomy (RP) develop biochemical recurrence, the rate of which increases to ~50% in high risk patients, with adverse features such as positive margins & seminal vesicle invasion. Postop salvage radiotherapy (SRT) to the prostate bed improves biochemical progression free survival (bPFS). We sought to evaluate the benefit of SRT and predictors of bPFS. Methods: Patients who received SRT from Jan11 to Dec15 were retrospectively analysed. All patients had prostate bed radiotherapy (66Gy/33#/6.5wks). Hormone therapy (HT), when used was for a short duration of 3-6 months. PSA relapse after SRT was defined as serum PSA rising above the posttreatment nadir to a level of ≥0.2 ng/mL or by the initiation of HT after completion of SRT. The bPFS was calculated as the time from start of SRT till date of undetectable PSA, analysed by Kaplan-Meier estimates and log-rank test. Results: Overall, 111 patients were analysed. Median follow-up was 46 (range; 6-80) months. 46% (51/111) patients received HT. The median pre-SRT PSA was 0.4 ng/mL (range, 0.07 to 4.9). The bPFS rate was 60.4% overall, 65%for those with a pre-SRT PSA (ng/mL) level of ≤0.5 (n = 74), 53.6% for those with a PSA of > 0.5 to ≤1.5 (n = 28), 44.4% for those with a PSA of > 1.5 (n = 9); (p = 0.33). There was no significant difference in bPFS rates for pre-SRT PSA of ≤0.2 compared to PSA ≤0.5. Significantly improved bPFS rates were seen with an interval of > 6m from detectable PSA to start of SRT (69% vs. 46.5%: p = 0.026), and a trend towards better bPFS rates when the time interval was > 24m from RP to first detectable PSA (73% vs. 53%: p = 0.08). However, bPFS was similar in the proportion of patients (46%) who had HT compared to those (54%) who did not have HT. Conclusions: We have shown that there was no significant difference in bPFS rates between early (detectable PSA at 0.2) and deferred SRT and our data supports the practice of deferred SRT prior to PSA going above 0.5. Short course of HT was not shown to improve bPFS. The ongoing RADICALS and RAVE trials will further clarify these aspects.

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Comparison of biochemical recurrence-free survival after radical prostatectomy among men in active surveillance following grade reclassification and men newly diagnosed with similar grade disease.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.117 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 117-117

Author(s):

Clarissa P. Diniz ◽

Ballentine Carter ◽

Jonathan I. Epstein ◽

Mufaddal Mamawala

Keyword(s):

Radical Prostatectomy ◽

Active Surveillance ◽

Biochemical Recurrence ◽

Cox Regression ◽

Cox Model ◽

Recurrence Free Survival ◽

Grade Group ◽

Free Survival ◽

Grade Groups ◽

Group 2

117 Background: Stakeholders in a Patient-Centered Outcomes Research grant questioned the clinical implications of biopsy grade reclassification (GR) while on active surveillance (AS). Methods: We conducted a retrospective analysis of men undergoing radical prostatectomy (RP) from 1995-2015 at Johns Hopkins and identified 4 groups; 76 men in AS underwent RP following GR from Gleason score (GS) 6 to GS 7(3+4) [grade group 2], 2947 men underwent immediate radical prostatectomy (IRP) following a diagnosis of grade group 2, 122 men in AS underwent RP following GR to GS ≥ 7(3+4) [grade groups ≥ 2], and 4433 men underwent IRP following a diagnosis of grade groups ≥ 2. Biochemical recurrence free survival (bRFS) was the outcome of interest that was assessed using Kaplan Meir curves and a multivariate Cox regression model. Results: Men on AS had a higher proportion of low volume cancer (p <0.001; p <0.001) as compared to the IRP groups for both biopsy grade group 2 and biopsy grade groups ≥ 2, respectively. On the Kaplan Meier curve, bRFS was higher for men in the AS cohort compared to IRP group for both biopsy grade group 2 (p = 0.071) and for biopsy grade groups ≥ 2 (p = 0.046). However, on the multivariate Cox model adjusting for age at treatment, cancer volume, and PSAD, the difference in bRFS between the AS and IRP group was no longer significant; HR = 0.61 (95% CI, 0.23 to 1.67) for biopsy grade 2, HR = 0.77 (95% CI, 0.41 to 1.46) for biopsy grades ≥ 2. Conclusions: AS patients that are reclassified to grade group 2 and those reclassified to grade group 2 or above have a higher chance of bRFS after treatment as compared to those undergoing IRP with similar grades. This could help inform decisions regarding the risk of entering an AS program. [Table: see text]

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Conditional biochemical recurrence-free survival and cancer-specific mortality after radical prostatectomy at long term follow-up.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.55 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 55-55

Author(s):

Silvia Garcia Barreras ◽

Rafael Sanchez-Salas ◽

Igor Nunes-Silva ◽

Fernando P. Secin ◽

Victor Srougi ◽

...

Keyword(s):

Radical Prostatectomy ◽

Biochemical Recurrence ◽

Cox Regression ◽

Primary Treatment ◽

Cumulative Probability ◽

Recurrence Free Survival ◽

Free Survival ◽

Specific Mortality ◽

Cancer Specific Mortality

55 Background: To estimate the conditional biochemical recurrence-free survival (BCR) rates and cancer-specific mortality (CSM) for men with clinically localized prostate cancer (PCa) treated with radical prostatectomy (RP) at our institution. Methods: A total of 3576 patients underwent laparoscopic radical prostatectomy (LARP) and 2619 men were treated with robotic radical prostatectomy (RARP) in the last 15 years. BCR of primary treatment was defined as PSA > 0.2 ng/dl. PCa death was defined as patients who died with metastasis in an androgen independent setting. Kaplan-Meier and Cox regression methods were used to estimate the conditional survival probabilities and CSM. Results: The median follow-up was 8.49 years (IQR 4.01-12.97). A total of 92 (1.48%) patients (80 LARP and 12 RARP) died of disease. Positive surgical margins (PSM) were identified in 1202 patients (19.4%); of these, 664 (55.24%) had organ confined disease and 523 (43.51%) had extraprostatic extension (EPE). BCR-free survival rate was found significantly higher with RARP (83% vs 77% for LARP at 10 years; p < 0.001). For patients with PSA < 10 ng/dl BCR-free survival at 10 years was 80% vs 64% for PSA 10-20 ng/dl, and 59% for PSA > 20ng/dl; p > 0.001. Conditional probability of BCR after surgery 1st year was 6.7%. Those who reach the 2nd year of surgery without recurrence had a relapse probability of 4%, (cumulative probability 9.8%) That probability falls to 3.5% after the 3rd year (cumulative probability 13%), 2% after the 4th year (cumulative probability 15%) and is 2.1% after the 5th year (cumulative probability 17%). After 10 years of follow-up without recurrence, the possibility of relapse was 0.8%, (cumulative probability 21%). Men without BCR had a clinical trend of higher CSM at 10 years (7% vs 2% no BCR; p 0.06). Within the patients who develop BCR, those with BCR in the first three years of follow-up had higher CSM (9% vs 4% for BCR after 3 years; p 0.04). Conclusions: BRC free survival outcomes are affected by risk factors associated with type of surgery and prognosis in PCa. The period elapsed from RP is associated with BCR-free survival and the risk of recurrence decrease with increasing survival.

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PUMA and NOXA Expression in Tumor-Associated Benign Prostatic Epithelial Cells Are Predictive of Prostate Cancer Biochemical Recurrence

Cancers ◽

10.3390/cancers12113187 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3187

Author(s):

Sylvie Clairefond ◽

Benjamin Péant ◽

Véronique Ouellet ◽

Véronique Barrès ◽

Zhe Tian ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Epithelial Cells ◽

Biochemical Recurrence ◽

Cox Regression ◽

Prognostic Significance ◽

Tissue Microarrays ◽

Regression Analyses ◽

Kaplan Meier ◽

Puma Expression

Background: Given that treatment decisions in prostate cancer (PC) are often based on risk, there remains a need to find clinically relevant prognostic biomarkers to stratify PC patients. We evaluated PUMA and NOXA expression in benign and tumor regions of the prostate using immunofluorescence techniques and determined their prognostic significance in PC. Methods: PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples (n = 285). TMAs were constructed using two cores of benign tissue and two cores of tumor tissue from each patient. Association between biomarker expression and biochemical recurrence (BCR) at 3 years was established using log-rank (LR) and multivariate Cox regression analyses. Results: Kaplan–Meier analysis showed a significant association between BCR and extreme levels (low or high) of PUMA expression in benign epithelial cells (LR = 8.831, p = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, p < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, p < 0.001) in Kaplan–Meier and in a multivariate Cox regression analyses (HR: 2.935 (1.645–5.236), p < 0.001). Conclusions: The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.

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