Comparison of Contemporary Treatment Options for Early Prostate Cancer: A Single Institution Series

Research Article

Austin J Radiat Oncol & Cancer. 2016; 2(1): 1018.

Comparison of Contemporary Treatment Options for Early Prostate Cancer: A Single Institution Series

Musunuru HB¹, Klotz L², Vesprini D¹, Morton G¹, Cheung P¹, Chung H¹, Sethukavalan P¹, Ghanem G¹, Zhang L¹, Mamedov A¹, Jethava V², D’Alimonte L¹, Deabreu A¹, Jain S³, Yamamoto T² and Loblaw DA1,4*

¹Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada

²Department of Surgical Urology, Sunnybrook Health Sciences Centre, Canada

3Centre for Cancer Research and Cell Biology, Queens University Belfast, Canada

4Department of Health Policy, Measurement and Evaluation, University of Toronto, Canada

*Corresponding author: Andrew Loblaw, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Department of Health Policy, Measurement and Evaluation, University of Toronto, Canada

Received: June 01, 2016; Accepted: June 08, 2016; Published: June 10, 2016


Purpose: To evaluate outcomes of low-risk prostate cancer patients managed with competing treatments, in a single institution.

Methods: Patients with low-risk cancer (cT1-T2a and Gleason score 6 and PSA<10ng/ml) from 2006-2008 were included. Treatment details and worst late toxicities (Common Terminology Criteria for Adverse Events version 3.0) were retrieved through retrospective chart review. Biochemical relapse-free survival following primary (pbRFS) and salvage treatments (sbRFS), metastasis-free (MFS), cause-specific (CSS) and overall survival (OS) were also evaluated.

Results: In 582 patients, treatment options were active surveillance (AS, N=181), radical prostatectomy (RP, N=59), external beam radiation (EBRT, N=66; 76 Gy in 38 fractions), low-dose rate brachytherapy (LDR, N=192), stereotactic ablative radiotherapy (SABR, N=84; 35Gy in 5, weekly fractions). Median follow-up was 72.8 months. Six-year pbRFS and sbRFS were 94.0% and 95.8%, 84.1% and 98.3%, 92.1% and not applicable, 94.4% and not applicable, 95.8% and 98.7%; for AS, RP, EBRT, LDR and SABR, respectively. In multivariate analysis, RP had inferior pbRFS compared to EBRT, LDR or SABR (p-value <0.05) and a trend for AS (p-value 0.15). CSS, MFS and OS were similar. Toxicities were minimal in AS cohort. EBRT patients had higher rates of dysuria (19.7%), transurethral resection of prostate (6.1%) and hematochezia (7.6%). One patient each in EBRT, LDR and SABR cohorts had grade 4 toxicity. Toxicity data was not available for RP.

Conclusion: In primary setting all treatment modalities apart from RP had a 6-year pbRFS >90%, likely due to selection bias. Following salvage therapy, sbRFS was >95.0% in AS, RP and SABR cohorts.

Keywords: Prostate cancer; External beam radiotherapy; Stereotactic body radiotherapy; Brachytherapy; Active surveillance; Biochemical outcomes


AS: Active Surveillance; RP: Radical Prostatectomy; LDR: Low- Dose Rate Brachytherapy; EBRT: External Beam Radiation; SABR: Stereotactic Ablative Radiotherapy; PSA: Prostate-Specific Antigen; TURP: Transurethral Resection of Prostate; IPSS: International Prostate Symptom Score; 3DCRT: Three-Dimensional Conformal Radiation; IMRT: Intensity Modulated Radiation Therapy; PTV: Planning Target Volume; pbRFS: Primary Biochemical Relapse- Free Survival; sbRFS: Salvage Biochemical Relapse-Free Survival; AUA: American Urology Association; ASTRO: American Society for Radiation Oncology; HDR: High-Dose Rate Brachytherapy; MFS: Metastasis-Free Survival; CSS: Cause-Specific Survival; OS: Overall Survival; GU: Genitourinary; GI: Gastrointestinal; CTCAE: Common Terminology Criteria for Adverse Events; APC: Argon Plasma Coagulation; CI: Confidence Intervals; SAS: Statistical Analysis Software; ADT: Androgen Deprivation Therapy; NCCN: National Comprehensive Cancer Network; EAU: European Association of Urology; ASCO: American Society of Clinical Oncology


Management options for low-risk localized prostate cancer include Active Surveillance (AS), radical prostatectomy (RP), radical radiation including Low-Dose Rate Brachytherapy (LDR), External Beam Radiation (EBRT) and more recently SABR (stereotactic ablative radiotherapy) [1,2]. Designing randomized studies to compare these options has proven to be challenging due to predetermined patient’s choice of treatment, influenced by multiple factors [3]. Comparison of all available treatment options including contemporary radiotherapy modalities like SABR has not been performed on a single platform. Paucity of such data led to the inception of this study, comparing outcomes in low-risk prostate cancer patients, managed in a single high-volume academic institution.


This study was approved by Sunnybrook Health Sciences Centre, Toronto; Research Ethics Board (REB 066-2011).


Low-risk prostate cancer patients diagnosed on initial biopsy (reviewed by Uropathologist) and managed on institution specific protocols from January 2006 – December 2008 were selected based on retrospective chart review. Eligibility criteria consisted of clinical stage T1-T2a and Gleason sum score 6 and prostate-specific antigen (PSA) <10ng/ml. Management protocols were either AS, open RP, EBRT, LDR or SABR. Choice of treatment was based on baseline urinary symptoms, prostate volume, fitness for anesthesia and predominantly patient preference. Transurethral resection of prostate (TURP), prostate size >60cm3or pubic arch interference made patients ineligible for low-dose rate brachytherapy; International Prostate Symptom Score (IPSS)>19 or prostate size >90cm3 excluded them from SABR studies.


AS was initiated in 1995 and data has been prospectively collected for over 1000 patients to date [4]. In short, patients on an AS pathway have 3 monthly PSAs, clinical examination and protocol biopsies every 3 years, following reconfirmation biopsy at year 1. Clinical progression, change in PSA kinetics with a PSA doubling time less than 3 years or pathological upgrading; constitute the triggers for active treatment.

Patients in the surgical cohort underwent standard open RP.

Prostate EBRT was delivered as three-dimensional conformal radiation (3DCRT) or intensity modulated RT (IMRT) with a median dose of 76Gy in 38 fractions. Planning target volume (PTV) margin for prostate was 10mm except posteriorly (7mm).

LDR brachytherapy patients had standard Iodine-125 interstitial implant with a minimal peripheral dose of 145Gy [5].

SABR patients were treated on a phase I/II prospective study (pHART3) [6]. Gantry-based SABR was delivered to a dose of 35Gy in 5, weekly fractions. A 4mm margin was added to the prostate for PTV. Treatment was delivered using step and shoot IMRT, gold seed fiducials were used for image guidance.

Study endpoints

Co-primary endpoints were biochemical relapse-free survival following primary (pbRFS) and local salvage therapies (sbRFS).

Patients on AS who did not receive treatment were censored as relapse-free at the time of bRFS analysis. Date of registration (i.e., first positive) biopsy was set as day zero for these patients.

In RP patients, date of surgery was day zero. Biochemical failure was defined as per American Urology Association (AUA)/American Society for Radiation Oncology (ASTRO) consensus (a confirmed PSA value > 0.2 ng/ml or one PSA > 0.4 ng/ml) [7]. Patients who had adjuvant radiotherapy were included in the primary RP cohort. Data about salvage radiotherapy was used to compute sbRFS. Biochemical failure following postoperative radiation was defined as per Phoenix criteria (nadir PSA following adjuvant radiation + 2.0ng/ml) [8], to facilitate fair comparison of modalities.

For EBRT and SABR patients, time zero was defined as the start of radiation. Phoenix definition [8] was used to identify biochemical failure following primary or salvage therapy. Salvage therapy could be either RP or focal high-dose rate (HDR) brachytherapy (Institutional phase I/II study, NCT01583920).

Secondary endpoints include Metastases-Free Survival (MFS), Cause-Specific Survival (CSS), Overall Survival (OS) and toxicities.

Electronic charts were reviewed to collect data about clinically significant bladder and bowel toxicities for patients managed on AS and radiotherapy protocols. Data about toxicity for study and nonstudy patients was collected using a standardized proforma at every clinic visit and documented in the chart. This data was retrospectively reviewed by a single physician to identify clinically significant worst toxicity at any point in the late follow-up period (>3 months following treatment), in order to minimize inter-observer bias and discrepancy associated with retrospective and prospective cohorts. For Genitourinary (GU) toxicities, significant dysuria needing more than one bladder medication was graded as grade 2 toxicity (Common Terminology Criteria for Adverse Events [CTCAE] version 3.0 [9]); late catheterization, late hematuria with clots needing catheter placement or admission, TURP, urethral stricture and fistula were reported separately.

For gastrointestinal domain, late GI bleed related to radiation needing any medical intervention in the form of steroid or mesalamine suppositories, 4% formalin therapy or argon plasma coagulation (APC) was reported as grade 2 toxicity. In addition, patients needing APC to control bleeding were reported separately as this is considered to be significant bleeding. GI stricture and fistula were recorded. Descriptive toxicity (where possible) rather than CTCAE grading was used to aid clarification.

Statistical analyses

Descriptive analysis was reported as median for continuous variables, and proportions for categorical variables. Primary bRFS was computed using Kaplan–Meier curve with 95% confidence intervals (CI). Patients who had biochemical control following salvage therapy were censored as disease-free at the time of sbRFS analysis. Information about patients with metastatic disease, deaths from prostate cancer and from all causes including prostate cancer, was used to compute MFS, CSS and OS, respectively.

As RP is considered to be a very well established treatment for prostate cancer, pair-wise comparison of primary bRFS between RP and each treatment (AS, LDR, SBRT, or EBRT) was conducted using log-rank test.

Univariate and multivariate analyses were performed to identify covariates predicting pbRFS after primary treatment. Age, age >65 versus =65 years, PSA at baseline (log scale), baseline PSA = 4.0ng/ml versus <4.0ng/ml, clinical stage T1 versus T2 and different treatment modalities (using RP as the reference treatment) were used as covariates in these analyses.

Fisher exact test was used to compare GU and GI toxicities. A second comparison was performed for only SABR and EBRT cohorts, given comparable patient selection criteria for these treatments.

All analyses were performed using Statistical Analysis Software (SAS version 9.2 for Windows).


Five hundred and eighty-two patients were included in this study. One hundred and eighty-one patients were managed with AS, 59 patients underwent RP, 192 had LDR, 84 patients were treated with SABR and 66 patients had EBRT. Median follow-up for the entire cohort was 72.8 months (range 7.5-101.7months). Demographic details are summarized in Table 1. Biochemical and survival outcomes are described in Table 2; toxicities in Table 3.