Faculty of Oncology

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    OUTCOMES AND DETERMINANTS OF PSA BASED HIGH RISK PROSTATE CANCER PATIENTS TREATED WITH CURATIVE RADIATION AT KORLE BU TEACHING HOSPITAL ACCRA, GHANA
    (ARYEETEY NAA ADORKOR, 2022-03-01) ARYEETEY, NAA ADORKOR
    BACKGROUND: Prostate cancer (CAP) is one of the commonest male cancers worldwide. Usually described as a slow growing malignancy, treatment outcomes are often favourable with five-year overall survival quoted at 80% even in the metastatic setting of disease. Risk categorisation prior to treatment using several parameters including but not limited to prostate specific antigen (PSA), Gleason score, clinical stage and recently molecular features allows for tailored treatment predicated on life expectancy and the risk of recurrence. Local treatment is with radical prostatectomy, external beam radiotherapy and brachytherapy. The management of high risk localised prostate cancer patients with high PSA remains a challenge as there is paucity of data on treatment outcomes. External beam radiotherapy (EBRT) to doses above 70Gy with peri-radiotherapy androgen deprivation therapy (ADT) in the neoadjuvant, concurrent and adjuvant setting for 2-3 years is the recommended standard treatment for high risk disease. Partial implant brachytherapy, low dose rate permanent implant of radioactive isotopes (I125, Cs-131 and Pd 103), augmented with EBRT (45Gy-50Gy) is an alternative for local treatment of high risk disease. High dose rate brachytherapy (Ir-192 and Co-60) currently in use delivers doses upwards of 12Gy per fraction to the prostate gland. This can be used in the stead of low dose rate brachytherapy. Both options allow for dose escalation with reduced side effects to organs at risk. Treatment outcomes for patients with increasing PSA maybe inferior compared to those with low pre-treatment PSA levels represented by short time to biochemical failure and high biochemical failure rates, assuming the suspicion that patients with high pre-treatment PSA harbour early micro metastatic disease holds true. With evidence suggesting improved outcomes for localised treatment even in the presence of clinically evident metastasis, treatment outcomes are expected to be improved irrespective of pre-treatment PSA. The question though is whether outcomes will differ with increasing PSA levels. Aim: To compare the treatment outcomes of localised high risk prostate cancer patients treated with curative intent using radiation therapy based on their pre-treatment PSA levels and the effect of a Gleason grade of 5 as primary grade on treatment outcomes METHODOLOGY: In this retrospective chart review that combined descriptive and inferential study design, a cohort of patients treated from January 2010 to December 2014 were described for their demographic, tumour and treatment characteristics. A core group with localised high risk prostate cancer based on their PSA levels between 20-200ng/ml treated with curative intent with external beam radiotherapy alone (EBRT) or brachytherapy augmented by external beam radiotherapy(BRACHY+EBRT) with or without androgen deprivation therapy (ADT) were grouped based on their pre-treatment PSA levels. Group A had PSA 20-49.9 ng/ml Group B 50-99.9ng/ml and C 100-200ng/ml and followed up from date of diagnosis to 31st December 2020. The patients were analysed using inferential statistic for treatment outcomes; biochemical and overall survival using Kaplan Meier curves and compared using log rank test. Patients were also compared for biochemical and overall survival outcomes based on their primary Gleason grade and combined Gleason score. Kruskal Wallis test of means was used for univariate analysis of non-parametric data and Cox regression analysis for multivariate analysis. RESULTS: Eighty three percent of patients seen were evaluable for descriptive statistics (486 of 584). The median age at presentation was 67 years (range of 44-85 years). Adenocarcinoma was the commonest histology forming more than 99.6% of histologically diagnosed patients. The median PSA at presentation was 31.9ng/ml (interquartile range 20ng/ml-95ng/ml). Clinical stage T2N0 was the modal stage at diagnosis. Combined Gleason score was available for all but one patient with localised disease but only 88% of the patients had primary and secondary Gleason grades recorded. Majority of the patients seen had high risk disease (53%), 7% low risk, 21% intermediate risk and 18% patients with metastatic disease. Data was inadequate to risk categorise 1% of the patients. Approximately half of patients with localised disease did not receive their intended curative treatment. High risk patients had the highest default rate of 58%. External beam radiotherapy was the most used treatment modality. The mean dose for EBRT only was 72.42Gy, mean D90 was168.68Gy for brachytherapy only and for combination therapy the mean D90 of 109.60Gy and 45.35Gy for brachytherapy and EBRT respectively. Mean duration of treatment was for EBRT only was 8.9 weeks for the intended 7.5 weeks. Medical castration was the most used form of ADT. ADT was used for a mean of 14.6 months mainly in the high risk group. Four patients had bilateral total orchiectomy as lifelong ADT while 2 patients had radiotherapy concurrent with diethylstilbesterol (DES) and then for a total of 36 months. The core group was followed up for a median of 7.25 years (range 4-10.5 years). There was a statistically significant difference in biochemical failure free survival when patients were stratified on pre- treatment PSA with p-value of 0.033. Based on combined Gleason score, biochemical failure free survival approached statistical significance with a p-value of 0.083. There was no difference in biochemical failure free survival when compared based on primary Gleason grade The 5 and 10-year biochemical free survival ranged from 46-68% and 36%-62% respectively, highest for Group B. Group C did not reach the 10 year mark for follow-up. Stratified for primary Gleason grade, biochemical failure free survival was about 55% at 10 years for primary Gleason grade 2-3. Primary Gleason 5 had biochemical failure free survival of 52% at 10years. Gleason 4 did not reach the 10-year follow-up mark but it was below that for Gleason 5 at 6 years, 38%. The curves were not statistically significantly different from each other with a pvalue of 0.311. Nadir PSA value was found to be statistically significant for predicting biochemical failure free survival on both univariate and multivariate analysis. A Receiver operator characteristic (ROC) curve drawn to predict 4 year biochemical failure free survival based on the nadir PSA found 0.07ng/ml as the threshold PSA (p-value 0.047). Estimated overall survival rates were above 70% at 10 years irrespective of patient stratification; pre-treatment PSA, primary Gleason grade or combined Gleason score. Overall survival showed a trend towards statistical significance when patients were assessed based on their combined Gleason score (p-value 0.06). This was not the case for pre-treatment PSA or primary Gleason grade. The biochemical failure free survival for group A, did not translate into overall survival benefit. A planned systematic analysis to predict PSA cut off for curative treatment for localised high risk prostate cancer was abandoned due to the lack of difference in overall survival outcomes when patients were grouped based initial PSA. CONCLUSION: Demography (age) and histological types of prostate cancer patients seen at the hospital compares to the rest of the world. Survival outcomes for localised high risk prostate cancer patients treated with radiotherapy and ADT at the National Radiotherapy Oncology and Nuclear Medicine Centre (NRONMC) of the Korle Bu Teaching Hospital (KBTH) is also comparable to existing published datasets. In our analysis a high initial presenting PSA up to 200ng/ml influenced biochemical outcomes in favour of low initial PSA. There was no difference in overall survival outcomes. This suggests all patients should receive curative treatment irrespective of pre-treatment PSA (up to 200ng/ml) provided there is no clinical or radiologic evidence of metastasis. There were no predictors of overall survival but nadir PSA