Prostatectomy Prostate Specific Antigen Research Articles

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET–Based Salvage Radiotherapy for Recurrent Prostate Cancer

Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT.

Post radical prostatectomy prostate-specific antigen doubling-time kinetics: Observations of increasing versus decreasing doubling times.

e17002 Background: Biochemical recurrence (BCR) following radical prostatectomy (RP) is an unreliable predictor of distant metastatic progression or prostate cancer (PC) death, consequently resulting in overtreatment. Further, little has been published about active surveillance (AS) specific management recommendations. Herein, we validate the practicality of using the kinetics (change) of PSA doubling time (PSADT) to direct continued observation versus intervention. Methods: In a retrospective cohort analysis of 406 men with BCR (defined as adjuvant therapy or PSA > 0.2 ng/dl, x2), 284 men were monitored post RP with PSADT graphs for all patients, and the PSADT was characterized as increasing vs decreasing. Receiver-operator characteristic (ROC) curves were generated to assess the sensitivity/specificity/positive predictive value/negative predictive value of PSADT progression on treatment and prostate cancer specific mortality at 10 years post-RARP, respectively. Results: The median follow-up was 7.6 (IQR: 4.6-10.6) years. Of 284 men, 109 (38%) and 175 (62%) were in the no treatment versus treatment groups, respectively. 87% of men receiving treatment had a decreasing PSADT and 100% men with PCSM had a decreasing PSADT. ROC analysis showed 0.870 sensitivity and 1.0 specificity when predicting secondary treatment (AUC = 0.935) and 0.857 sensitivity and 0.50 specificity when predicting PCSM (AUC = 0.679). Conclusions: A decreasing PSADT is a sensitive and specific metric for predicting the need for secondary intervention. We also found all men who died of PC had a decreasing PSADT. Lastly an increasing DT predicts a benign course without need for treatment. The current findings suggest that the kinetics of PSADT, increasing versus decreasing, is an accurate metric for the need of treatment. A direct comparison between PSADT kinetics and PSADT is needed.

Outcomes and Prognostic Factors in Men Receiving Androgen Deprivation Therapy for Prostate Cancer Recurrence after Radical Prostatectomy

We sought to determine clinicopathological factors associated with early progression in men on androgen deprivation therapy as well as cancer specific and overall survival. We also assessed whether certain prostate specific antigen thresholds at androgen deprivation therapy initiation are associated with poorer outcomes. We identified 2,418 men with rising prostate specific antigen after undergoing radical prostatectomy at a single institution between 1987 and 2007 in a prospectively maintained registry. Early progression was defined as clinical progression within 2 years of initiating androgen deprivation therapy. The primary study outcome was cancer specific and overall survival. The risk of early progression while on androgen deprivation therapy was lower for prostate specific antigen doubling time 3 to less than 9 months (OR 0.19) and less than 9 months or longer (OR 0.10, each p <0.001) prior to androgen deprivation therapy. Independent predictors of cancer specific survival were metastatic disease at androgen deprivation therapy initiation (HR 2.60), prostate specific antigen 5 to 50 ng/ml (HR 2.68) and 50 ng/ml or greater (HR 4.33), and doubling time 3 to less than 9 months (HR 0.54) and 9 months or longer (HR 0.45, all p<0.001). Independent predictors of overall survival were prostate specific antigen 5 to 50 ng/ml (HR 3.10) and 50 ng/ml or greater (HR 5.20, each p <0.001). In men in whom androgen deprivation therapy was initiated for relapse after radical prostatectomy prostate specific antigen doubling time less than 3 months and prostate specific antigen 5 ng/ml or greater were adverse prognostic factors for early progression and cancer specific survival. Prostate specific antigen 5 ng/ml or greater also predicted shorter overall survival. Longer doubling time and prostate specific antigen less than 5 ng/ml were associated with lower risk and these men may not require immediate androgen deprivation therapy.

POD-11.04: PSA Nadir After Radical Prostatectomy Measured by Ultrasensitive Assay Predicts the Risk of Biochemical Relapse of Prostate Cancer

After successful radical prostatectomy prostate specific antigen (PSA) should become undetectable by conventional PSA assays. However, ultrasensitive PSA assay techniques allow considerably lower limit of detection than standard PSA assays. The objective of this study was to investigate weather the dynamic of postoperative ultrasensitive PSA decrease could predict the biochemical relapse of prostate cancer.

Predicting Prostate Cancer Biochemical Recurrence Using a Panel of Serum Proteomic Biomarkers

The pathological state of the prostate may be reflected by serum proteome in a man. We hypothesized that biomarkers are present in preoperative serum, which may be used to predict the probability of biochemical recurrence following radical prostatectomy. Mass spectrometry analysis was used to compare 52 men who experienced biochemical recurrence with 52 who remained biochemical recurrence-free for approximately 5 years after radical retropubic prostatectomy. A total of 30 matched pairs of recurrent and nonrecurrent serum samples were randomly selected as a training set for biomarker discovery and model development. Selected mass spectrometry peaks were combined with pre-radical retropubic prostatectomy prostate specific antigen in a multivariate algorithm to predict recurrence. The algorithm was evaluated using the remaining 22 recurrent and 22 nonrecurrent subjects as test samples. Protein identities of the selected mass spectrometry peaks were investigated. Two serum biomarkers for recurrence, P1 and P2, were combined with preoperative prostate specific antigen to predict biochemical recurrence. The ROC AUC for prostate specific antigen and the predicted outcome was 0.606 and 0.691 in the testing data, respectively. Using a single cutoff the samples were divided into 2 groups that were predictive of biochemical recurrence (p = 0.026). In contrast, preoperative prostate specific antigen did not differ between recurrent and nonrecurrent cases (Wilcoxon matched pairs test p = 0.07). The protein identity of P1 was determined to be a truncated form of C4a (C4a des-Arg). Preliminary data indicated that P2 was an N-terminal fragment of protein C inhibitor. In the current study population, which was matched on Gleason score and TNM staging, pre-radical retropubic prostatectomy prostate specific antigen retained no independent power to predict recurrence. However, by adding 2 proteomic biomarkers to preoperative prostate specific antigen the combined model demonstrated statistically significant value for predicting prostate cancer recurrence in men who underwent radical retropubic prostatectomy.

Predicting an Optimal Outcome After Radical Prostatectomy: The Trifecta Nomogram

The optimal outcome after radical prostatectomy for clinically localized prostate cancer is freedom from biochemical recurrence along with the recovery of continence and erectile function, a so-called trifecta. We evaluated our series of open radical prostatectomy cases to determine the likelihood of this outcome and develop a nomogram predicting the trifecta. We reviewed the records of patients undergoing open radical prostatectomy for clinical stage T1c-T3a prostate cancer at our center during 2000 to 2006. Men were excluded if they received preoperative hormonal therapy, chemotherapy or radiation therapy, if pretreatment prostate specific antigen was more than 50 ng/ml, or if they were impotent or incontinent before radical prostatectomy. A total of 1,577 men were included in the study. Freedom from biochemical recurrence was defined as post-radical prostatectomy prostate specific antigen less than 0.2 ng/ml. Continence was defined as not having to wear any protective pads. Potency was defined as erection adequate for intercourse upon most attempts with or without phosphodiesterase-5 inhibitor. Mean patient age was 58 years and mean pretreatment prostate specific antigen was 6.4 ng/ml. A trifecta outcome (cancer-free status with recovery of continence and potency) was achieved in 62% of patients. In a nomogram developed to predict the likelihood of the trifecta baseline prostate specific antigen was the major predictive factor. Area under the ROC curve for the nomogram was 0.773 and calibration appeared excellent. A trifecta (optimal) outcome can be achieved in most men undergoing radical prostatectomy. The nomogram permits patients to estimate preoperatively their likelihood of an optimal outcome after radical prostatectomy.

Prostate Cancers Scored as Gleason 6 on Prostate Biopsy are Frequently Gleason 7 Tumors at Radical Prostatectomy: Implication on Outcome

Differentiation between Gleason score 6 and 7 in prostate biopsy is important for treatment decision making. Nevertheless, under grading errors compared with the actual pathological grade at radical prostatectomy are common. We compared the characteristics and outcomes of tumors that were scored 6 on prostate biopsy but were 7 on subsequent radical prostatectomy pathological evaluation to those in tumors with a consistent rating of Gleason score 6 or 7 at biopsy and surgery. We performed a retrospective database analysis from our referral center (1989 to 2004). We compared pre-prostatectomy characteristics, radical prostatectomy pathological features and the post-radical prostatectomy prostate specific antigen failure rate, defined as any 2 consecutive detectable prostate specific antigen measurements, in 3 subgroups of patients, including 156 with matched Gleason score 6 in the prostate biopsy and radical prostatectomy, 205 with upgraded Gleason score 6/7, that is prostate biopsy Gleason score 6 and radical prostatectomy Gleason score 7, and 412 with matched Gleason score 7 in the prostate biopsy and radical prostatectomy. Radical prostatectomy Gleason score matched the prostate biopsy score in 38.2% of biopsy Gleason score 6 and 81.4% of biopsy Gleason score 7 cases. Higher prostate specific antigen was associated and an increased percent of cancer in the prostate biopsy was predictive of discordance between the prostate biopsy and radical prostatectomy Gleason scores (p <0.001). Margin (p = 0.0075) or seminal vesicle involvement (p = 0.0002), cancer volume (p <0.001) and the prostate specific antigen failures rate (p = 0.014) were significantly higher in under graded Gleason score 7 cancer compared to those in matched Gleason score 6 cases. However, they were comparable to those with a matched Gleason score 7 tumor grade (p = 0.66). Almost half of tumors graded Gleason score 6 at biopsy are Gleason score 7 at surgery. Upgraded Gleason score 6 to 7 tumors have outcomes similar to those of genuine Gleason score 7 cancer. For prostate biopsy Gleason score 6 tumors clinicians should consider the overall likelihood of tumor upgrading as well as specific patient characteristics, such as prostate specific antigen and the percent of tumor in the prostate biopsy, when contemplating treatments that are optimized for low grade tumors, including watchful waiting or brachytherapy.

PERCENT FREE PROSTATE SPECIFIC ANTIGEN IS NOT AN INDEPENDENT PREDICTOR OF ORGAN CONFINEMENT OR PROSTATE SPECIFIC ANTIGEN RECURRENCE IN UNSCREENED PATIENTS WITH LOCALIZED PROSTATE CANCER TREATED WITH RADICAL PROSTATECTOMY

We studied the controversial relationship of percent free prostate specific antigen (PSA) with organ confined prostate cancer and PSA failure after radical prostatectomy. We tested the characteristics of the percent free PSA monoclonal Immulite DPC Immunoassay (Diagnostic Products Corp., Los Angeles, California) for predicting organ confinement in 698 consecutive unscreened men treated only with radical prostatectomy between 1995 and 2000. In addition, we assessed the ability of percent free PSA to predict post-radical prostatectomy PSA failure, defined as PSA 0.1 ng./ml. or greater, in a subset of 581 men in whom followup was available. All statistical analyses were repeated for stage T1c cancer with PSA between 2 and 10 ng./ml. On univariate analyses percent free PSA achieved significance for predicting organ confined disease at all clinical stages (p <0.001) and for stage T1c cancer with PSA between 2 and 10 ng./ml. (p = 0.012). However, significance dissipated after controlling for total PSA, biopsy Gleason sum and clinical stage (p = 0.135 and 0.851, respectively). In univariate Cox models percent free PSA failed to predict PSA failure across stages (p = 0.341), as well as in stage T1c cancer (p = 0.93). In multivariate analyses controlling for traditional PSA biopsy grade and clinical stage (p <0.001), percent free PSA failed to contribute to predicting PSA failure (p = 0.342). In the stage T1c subset biopsy Gleason sum (p <0.001) and PSA (p = 0.018) remained significant, in contrast to percent free PSA (p = 0.237). Percent free PSA has no independent, statistically significant association with organ confined status or posttreatment PSA outcome in unscreened patients who undergo radical prostatectomy for localized prostate cancer.

PRETREATMENT PROSTATE SPECIFIC ANTIGEN DOUBLING TIMES: USE IN PATIENTS BEFORE RADICAL PROSTATECTOMY

Purpose We determined whether pre-radical prostatectomy prostate specific antigen (PSA) doubling time could predict pathological stage at radical prostatectomy or PSA failure postoperatively. We also sought to compare PSA doubling times from men with prostate cancer treated with radical prostatectomy to a group treated with radiation therapy. Materials and Methods Detailed followup was available for 150 patients with clinically localized prostate cancer who underwent radical prostatectomy from January 1993 to August 1995. PSA doubling time was calculated for all patients with 3 or more pre-radical prostatectomy PSA levels using linear regression. We assessed the association between PSA doubling time and PSA failure, pathologic stage at radical prostatectomy, final PSA before treatment and Gleason score. We compared our PSA doubling time values and distribution to a published series of patients with prostate cancer who had undergone radiation therapy. Results A total of 56 patients had 3 or more PSA values before treatment. Median followup was 17.3 months. PSA doubling time did not correlate with PSA failure, final PSA or Gleason score, but it did with pathological stage at radical prostatectomy (p = 0.0035 for positive margins, p = 0.025 for positive seminal vesicles). Our PSA doubling time and PSA failure rates did not differ from the radiation therapy population with similar followup times. Conclusions Although studies from the radiation literature have shown PSA doubling time to be useful in predicting PSA failure after treatment for prostate cancer, our results do not confirm this finding. We did find a correlation with pathologic stage at radical prostatectomy, and so longer followup with more patients may confirm this in the future. We also found no significant differences in PSA doubling time between our patients and a group treated with radiation. At least for this parameter, patients with prostate cancer referred for radical prostatectomy and radiation therapy may be similar.

Preliminary report on 10 patients treated with radiotherapy after radical prostatectomy for isolated elevation of serum PSA levels

Since 1987, 10 patients have been treated with irradiation to a limited pelvic volume for elevation of serum prostate-specific antigen (PSA) level above expected post-radical prostatectomy levels without clinical or radiological evidence of either metastatic or locoregional disease. The patients were treated 3 to 43 months after radical prostatectomy, using bilateral 120° arcs to deliver 6000 cGy to the prostatic bed. The pathologic findings of the initial surgical specimens for all patients were reviewed. Eight patients had pathologic Stage C disease, and five patients had one or more positive margins. All patients had negative staging lymphadenectomies. After irradiation, eight patients had decreases in PSA levels indicative of response of isolated local disease. Though preliminary, these results suggest that post- prostatectomy PSA levels are useful for detecting subclinical local recurrence or persistence in the prostatic bed, as well as monitoring these patients' response to therapy. The value of this elective treatment remains to be documented.

The Value of Serum Prostate Specific Antigen Determinations Before and after Radical Prostatectomy

We evaluated serum prostate specific antigen before and after radical prostatectomy. In 100 consecutive patients who underwent radical prostatectomy, preoperative prostate specific antigen levels tended to increase with the increasing severity of pathological stage. However, even at levels of greater than 10ng. per ml. the positive and negative predictive values (78 and 61 per cent, respectively) of prostate specific antigen to predict extracapsular disease were not sufficient to make this test useful alone for staging. In theory, after radical prostatectomy prostate specific antigen should be zero if no remaining prostatic tissue is present. Tests of precision and analytical sensitivity in our laboratory using a commercial prostate specific antigen assay revealed that a value of 0.4ng. per ml. or more is different from zero at a greater than 95 per cent confidence level. With this guideline we evaluated the meaning of prostate specific antigen levels 3 to 6 months after radical prostatectomy in 59 men. Among men whose prostate specific antigen level was less than 0.4ng. per ml. only 9 per cent demonstrated recurrence as evidenced by the development of positive bone scan or progressively elevated prostate specific antigen levels within 6 to 50 months. Alternatively, in men whose 3 to 6-month prostate specific antigen level was 0.4ng per ml. or more there was evidence of recurrence in 100 per cent within 6 to 49 months (p less than 0.0001). Progressively elevated (more than 0.4ng. per ml.) prostate specific antigen levels preceded recurrence from 12 to 43 months in all 6 patients who had positive bone scans, while increasing prostate specific antigen levels since radical prostatectomy have continued from 9 to 65 months in the 11 patients who have no radiological evidence of recurrent disease to date. Prostatic acid phosphatase serum values after radical prostatectomy were not useful to predict persistent disease. Prostate specific antigen values 3 to 6 months after radical prostatectomy are a sensitive indicator of persistent disease after radical prostatectomy and often precede other evidence of this occurrence by many years. This fact may alter concepts about surgical results, and possibly shorten and sharpen clinical studies involving adjuvant therapy after radical prostatectomy.