Favorable Intermediate-risk Prostate Research Articles

Stereotactic focal radiotherapy as an alternative treatment for low-risk prostate cancer: Results of a single-arm monocenter Phase-II trial.

Since radical treatments in low risk prostate cancer do not improve overall survival in comparison to active surveillance, preserving quality of life (QOL) remains the key objective. Active surveillance of indolent prostate cancer avoids curative treatment side-effects but necessitates repeated biopsies. Focal stereotactic body radiation therapy (focal SBRT) may be an alternative. This non-randomized Phase-II trial examined the feasibility and safety of focal SBRT for low and favorable intermediate-risk prostate cancer. Patients were recruited in 2016-2019 if they had: localized CAPRA ≤ 3 prostate adenocarcinoma; an isolated PIRADS≥4 macroscopic tumor on MRI; WHO Performance Status 0-1; and no major urinary symptoms. 36.25 Gy (80% isodose prescription) were delivered in 5 fractions every other day. Primary outcome was delay between focal SBRT and salvage-treatment initiation. Secondary outcomes were: acute/late genitourinary/rectal toxicity; biological, clinical and MRI local control; and change in QOL measures. Over a median follow-up of 36 months, salvage prostatectomy in the 24 eligible patients was never required. Three-year biochemical progression-free survival was 96%. The single biochemical recurrence was a small (2-mm) Gleason 6 (3 + 3) lesion in the non-irradiated lobe. All 19 patients with ≥1 post-treatment MRI evaluations demonstrated complete radiological response. Acute/late grade ≥3 toxicities did not occur: all acute toxicities were grade-1 genitourinary (38% patients), grade-2 genitourinary (8%), or grade-1 rectal (13%) toxicities. There was one (4%) late grade-1 genitourinary toxicity. QOL was unchanged at last follow-up, as shown by IPSS (2.86 to 3.29, p>0.05), U-QOL (0.71 to 0.67, p>0.05), and IIEF5 (the 14 initially potent patients maintained potency (IIEF5 > 16)). Focal SBRT is feasible, well-tolerated, and preserves QOL. This innovative robotized approach challenges active surveillance.

Comparative effectiveness of low-dose-rate brachytherapy with or without external beam radiotherapy in favorable and unfavorable intermediate-risk prostate cancer

We compared clinical outcomes associated with seed brachytherapy (SEED-BT) alone and SEED-BT plus external-beam radiotherapy (EBRT) for intermediate-risk prostate cancer using propensity score-matched analysis. From 2006 to 2011, 993 patients diagnosed with intermediate-risk were treated with either SEED-BT alone (n = 775) or SEED-BT plus EBRT (n = 158) at 3 tertiary hospitals. In the propensity score-matched analysis (102 pairs), median follow-up was 95 months (range 18–153 months). The 8-year biochemical recurrence-free rate (bRFR) was significantly better with SEED-BT alone than with combined radiotherapy (93.3% vs. 88.4%; HR 0.396; 95% CI 0.158–0.991). Grade 2 or greater late genitourinary toxicities were significantly fewer with SEED-BT alone than with combined radiotherapy (21.0% vs. 33.2%; HR 0.521; 95% CI 0.308–0.881). Similarly, grade 2 or greater late gastrointestinal toxicities were significantly fewer with SEED-BT alone (0% vs. 12.2%; HR 0.125; 95% CI 0.040–0.390). For the unfavorable intermediate-risk subgroups, SEED-BT alone yielded a significantly better bRFR than the combined radiotherapy (HR 0.325; 95% CI 0.115–0.915). SEED-BT alone might be a better disease-management plan than SEED-BT plus EBRT for intermediate-risk prostate cancer regardless of favorable and unfavorable characteristics.

Lack of price transparency for prostate-directed radiation therapy relative to radical prostatectomy.

1579 Background: For patients with low to favorable-intermediate risk prostate cancer (PC), management with active surveillance, radical prostatectomy (RP), external beam radiation therapy (EBRT), and brachytherapy (BT) are all National Cancer Center Network-supported definitive monotherapy options. Because therapy is non-urgent and choosing therapy can be complex, patients routinely seek second opinions and cost can be an important consideration. Recent federal price transparency (PT) guidance requires hospitals to provide payer-negotiated prices for ≥300 common services in a “shoppable,” user-friendly, online format. 70 services, including RP, are specified, while the remainder are left to institutional discretion. Despite equipoise between radiation therapy (RT, inclusive of EBRT and BT) and RP in definitive treatment for PC, inclusion of prices for RT is optional. National Cancer Institute (NCI)-designated cancer centers (NCI-CC) are high volume referral centers who have the option to volunteer prices for RT; the rate at which NCI-CC choose to report payer-negotiated price estimates for prostate-directed RT is unknown. We hypothesize that reporting rates for BT and EBRT are significantly lower than for RP. Methods: Through online query, we identified “shoppable” price tools for NCI-CC in December 2021. Using billing codes and keyword searches, we queried these price tools for cost estimates for RP, EBRT (delivered using intensity modulated radiation therapy), and BT. Descriptive statistics, include frequency counts and proportions, were performed. The rate of reporting of “shoppable,” negotiated prices for each therapy was assessed. These rates were compared using the chi-squared test (significance level of α = 0.05). Results: Of the 63 NCI-CC offering clinical care, 58 (92%) published “shoppable” tools. 6 (10%), 7 (11%), and 51 (81%) published “shoppable” prices for EBRT, BT, and RP, respectively, demonstrating a significantly higher rate of publication of prices for RP than for EBRT or BT ( P < 0.001). All of the published prices for BT were for high dose rate BT. The 11 Medicare Prospective Payment System–exempt NCI-CC had the highest rates of reporting “shoppable” prices at 91%, with 64%, 27%, and 36% including prices for RP, EBRT, and BT, respectively. Conclusions: Under existing regulations, patients with PC can obtain payer-negotiated price estimates for EBRT and BT from just roughly 10% of NCI-CC, while price estimates for RP are offered by > 80% of these institutions. This represents a potential obstacle to informed decision making, undermines the stated goals of US PT health policy, and the impact on utilization rates (or patient choice of therapy) is unknown. Moving forward, mandating the inclusion of common RT services (EBRT and BT) in “shoppable” price tools is a straightforward intervention that may be highly beneficial in this common cancer population.

Long-term and pathological outcomes of low- and intermediate-risk prostate cancer after radical prostatectomy: implications for active surveillance

PurposeThe safety of active surveillance (AS) in favorable intermediate-risk (FIR) prostate cancer (PCa) remains uncertain. To provide guidance on clinical decision-making, we examined long-term and pathological outcomes of low-risk and intermediate-risk PCa patients after radical prostatectomy (RP).MethodsThe study involved 5693 patients diagnosed between 1994 and 2019 with low-risk, FIR, and unfavorable intermediate-risk (UIR) PCa (stratification according to the AUA guidelines) who underwent RP. Pathological outcomes were compared, and Kaplan–Meier analysis determined biochemical recurrence-free survival (BRFS) and cancer-specific survival (CSS) at 5, 10, 15, and 20 years. Multiple Cox regression was used to simultaneously control for relevant confounders.ResultsThose at FIR had higher rates of upgrading and upstaging (12.8% vs. 7.2%, p < 0.001; 19.8% vs. 12.0%, p < 0.001) as well as pathological tumor and node stage (≥ pT3a: 18.8% vs. 11.6%, p < 0.001; pN1: 2.7% vs. 0.8%, p > 0.001) compared to patients at low risk. The 20-year BRFS was 69%, 65%, and 44% and the 20-year CSS was 98%, 95%, and 89% in low-risk, FIR, and UIR patients. On multiple Cox regression, FIR was not associated with a worse BRFS (HR 1.07, CI 0.87–1.32), UIR was associated with a worse BRFS (HR 1.49, CI 1.20–1.85).ConclusionPatients at FIR had only slightly worse pathological and long-term outcomes compared to patients at low risk, whereas the difference compared to patients at UIR was large. This emphasizes AS in these patients as a possible treatment strategy in well-counseled patients.

Intraprostatic calcification and biochemical recurrence in men treated with Cs-131 prostate brachytherapy.

237 Background: Vigneault et al. reported that baseline intraprostatic calcification (IC) was associated with a higher risk of biochemical recurrence (BCR) in men treated with I-125 prostate brachytherapy (PB). Cs-131 has different physical properties than I-125. We assessed whether baseline IC was associated with BCR in men treated with Cs-131 PB. Methods: We retrospectively reviewed the records of all low-risk (LR), favorable intermediate-risk (FIR), and unfavorable IR (UIR) prostate cancer patients treated with Cs-131 PB +/- external beam radiotherapy (EBRT) from 2/2011 to 7/2018 at our institution. Patients who received hormone therapy or those with &lt; 24 months follow-up were excluded. Baseline IC status (defined as 1 or more ICs ≥ 5 mm) and characteristics were determined on post-PB CT scans. Baseline patient characteristics were compared via χ2, Mann–Whitney U, or Student’s t-test. Predictors of BCR (Phoenix definition) were analyzed via Cox proportional hazards model and Kaplan–Meier survival curves were generated. Results: Two hundred and sixteen LR, FIR, and UIR prostate cancer patients treated with Cs-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1–111.4 months). 76 patients (35.2%) had baseline IC and 140 patients (64.8%) did not. Baseline disease characteristics did not differ significantly between patients with vs. without ICs. In patients with baseline IC, the median number of ICs was 1 (range 1–3), median length of largest IC was 9.1 mm (range 5.0–33.1), and median peak density of largest IC was 884 Hounsfield units (range 283–1744). ICs were most commonly present in the midgland (88.2%) and central (97.4%) regions. On univariate Cox analysis of all baseline disease, treatment, and IC characteristics, only initial PSA (p = 0.016) and NCCN risk group (p = 0.047) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with vs. without baseline IC was 97.7% vs. 93.8% (p = 0.40), respectively. Conclusions: In a cohort of LR and IR prostate cancer patients treated with Cs-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.

Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer?

ObjectiveAndrogen deprivation therapy (ADT) is beneficial for unfavorable intermediate-risk (IR) prostate cancer patients receiving curative radiotherapy (RT). However, for favorable IR patients the latest NCCN guidelines recommends RT alone. We retrospectively studied treatment patterns and outcomes of patients with IR prostate cancer in our institution over the past two decades.Materials and methodsThree hundred seventy-three IR prostate cancer patients treated with definitive RT between 5/2002–5/2016 were identified in an institutional review board approved database. All patients received conformal RT to the prostate while the vast majority did not receive nodal radiation. ADT was commenced 2 months prior to RT and was continued for 4 months after RT.ResultsCompared to RT alone, patients receiving combined RT+ ADT had more positive biopsy cores, higher pre-radiation PSA, more IR factors, and were more likely to receive pelvic lymph node radiation. However, there were no differences in failure either biochemical, local or distal, nor on survival between the favorable RT alone and the unfavorable RT+ ADT cohorts, suggesting a beneficial role for ADT. On multivariate analysis, patients 70 years or younger receiving RT alone were at increased risk for biochemical failure during a 6-year follow-up (HR 3.06, P = 0.025). Biochemical relapse free survival in patients ≤70 years who received RT alone was 82.1% vs 94.0% for RT + ADT (P = 0.030). There was no difference for combined treatment modality in patients > 70 years (P = 0.87).ConclusionsMen 70 years or younger with favorable IR prostate cancer treated with RT alone to 78 Gy are at increased risk of biochemical failure. Short term ADT should be considered in this cohort of men.

A biopsy-based genomic classifier to predict biochemical failure after definitive radiation without hormone therapy in a prospective cohort of intermediate risk prostate cancer.

68 Background: Recently, NCCN adopted the Zumsteg-Spratt subclassification to define NCCN favorable and unfavorable intermediate-risk prostate cancer (IR-PCa). NCCN unfavorable disease is recommended to receive combination androgen deprivation therapy (ADT) and radiotherapy. To determine if genomics could help identify a subset who may safely avoid ADT, we evaluated the Decipher genomic classifier (GC) in IR-PCa treated with dose-escalated image-guided radiotherapy (DE-IGRT) alone. Methods: Our cohort comprised of 121 patients with NCCN favorable (N = 49, 40%) and unfavorable (N = 74, 60%) IR-PCa, who received 78 Gy without ADT. Diagnostic needle biopsies with the highest Gleason score (GS) and %tumor involvement were macrodissected for RNA extraction. GC scores were determined from the Decipher prostate cancer classifier assay (GenomeDx Biosciences, San Diego, CA). Primary clinical endpoint was biochemical relapse ([BCR], PSA nadir + 2ng/ml) post-DE-IGRT. We compared association with BCR against known clinicopathologic prognostic indices and the NCCN risk strata. Results: With a median follow up of 7.5y, 24 (19%) patients experienced BCR. Individual clinical indices did not predict BCR-free survival rate (BFS). NCCN risk strata was however associated with a small but significant difference in BFS (5-y 93%, favorable vs 88%, unfavourable, P = 0.046). GC scores stratified 85 (70%), 19 (16%), and 17 (14%) men into low, intermediate, and high risk of recurrence; 5-y BFS were 95%, 89%, and 59%, respectively (P &lt; 0.001). On multivariable analysis, a hazard ratio of 4.71 (95% CI 1.81-12.28, P = 0.0015) for BCR was observed for the GC high risk group compared to low/intermediate; NCCN risk strata and intraductal variant did not achieve significance. Conclusions: In IR-PCa men treated with DE-IGRT monotherapy, Decipher GC was an independent predictor of BCR. While most men in this our cohort were stratified as NCCN unfavorable IR-PCa, the majority were GC low risk with excellent outcomes from DE-IGRT alone. In contrast, a minority with GC high risk had suboptimal outcomes, and may benefit from ADT intensification.