Purpose

Salvage high-dose-rate brachytherapy (sHDRBT) for locally recurrent prostate cancer after definitive radiation is associated with biochemical control in approximately half of patients at 3 to 5 years. Given potential toxicity, patient selection is critical. We present our institutional experience with sHDRBT and validate a recursive partitioning machines model for biochemical control.

Materials and methods

We performed a retrospective analysis of 129 patients who underwent whole-gland sHDRBT between 1998 and 2016. We evaluated clinical factors associated with biochemical control as well as toxicity.

Results

At diagnosis the median prostate-specific antigen (PSA) was 7.77 ng/mL. A majority of patients had T1-2 (73%) and Gleason 6-7 (82%) disease; 71% received external beam radiation therapy (RT) alone, and 22% received permanent prostate implants. The median disease-free interval (DFI) was 56 months, and median presalvage PSA was 4.95 ng/mL. At sHDRBT, 46% had T3 disease and 51% had Gleason 8 to 10 disease. At a median of 68 months after sHDRBT, 3- and 5-year disease-free survival were 85% (95% CI, 79-91) and 71% (95% CI, 62-79), respectively. Median PSA nadir was 0.18 ng/mL, achieved a median of 10 months after sHDRBT. Patients with ≥35%+ cores and a DFI <4.1 years had worse biochemical control (19% vs 50%, P = .02). Local failure (with or without regional/distant failure) was seen in 11% of patients (14/129), and 14 patients (11%) developed acute urinary obstruction requiring Foley placement and 19 patients (15%) developed strictures requiring dilation.

Conclusions

sHDRBT is a reasonable option for patients with locally recurrent prostate cancer after definitive RT. Those with <35%+ cores or an initial DFI of ≥4.1 years may be more likely to achieve long-term disease control after sHDRBT.

Background

To evaluate acute and late genitourinary and gastrointestinal toxicities and patient reported urinary and sexual function following accelerated, hypofractionated external beam radiotherapy to the prostate, seminal vesicles and pelvic lymph nodes and high dose rate (HDR) brachytherapy or stereotactic body radiation therapy (SBRT) prostate boost.

Methods

Patients at a single institution with NCCN intermediate- and high-risk localized prostate cancer with logistical barriers to completing five weeks of whole pelvic radiotherapy (WPRT) were retrospectively reviewed for toxicity following accelerated, hypofractionated WPRT (41.25 Gy in 15 fractions of 2.75 Gy). Patients also received prostate boost radiotherapy with either HDR brachytherapy (1 fraction of 15 Gy) or SBRT (19 Gy in 2 fractions of 9.5 Gy). The duration of androgen deprivation therapy was at the discretion of the treating radiation oncologist. Toxicity was evaluated by NCI CTCAE v 5.0.

Results

Between 2015 and 2017, 22 patients with a median age of 71 years completed accelerated, hypofractionated WPRT. Median follow-up from the end of radiotherapy was 32 months (range 2-57). 5%, 73%, and 23% of patients had clinical T1, T2, and T3 disease, respectively. 86% of tumors were Gleason grade 7 and 14% were Gleason grade 9. 68% and 32% of patients had NCCN intermediate- and high-risk disease, respectively. 91% and 9% of patients received HDR brachytherapy and SBRT prostate boost following WPRT, respectively. Crude rates of grade 2 or higher GI and GU toxicities were 23% and 23%, respectively. 3 patients (14%) had late or persistent grade 2 toxicities of urinary frequency and 1 patient (5%) had late or persistent GI toxicity of diarrhea. No patient experienced grade 3 or higher toxicity at any time. No difference in patient-reported urinary or sexual function was noted at 12 months.

Conclusions

Accelerated, hypofractionated whole pelvis radiotherapy was associated with acceptable GU and GI toxicities and should be further validated for those at risk for harboring occult nodal disease.

Purpose

Among Gleason pattern 4 types, cribriform pattern is associated with the worst outcomes. We hypothesized that larger cribriform patterns would be associated with increased Decipher scores and higher biochemical recurrence (BCR) risk in Gleason 3+4=7 prostatectomy patients.

Materials and methods

The slide from patients who underwent prostatectomy from January 2016 to March 2020 on which Decipher was performed was re-reviewed for Gleason score and cribriform patterns, with large cribriform defined as cribriform acini with greater than 12 lumens and simple cribriform as 12 or fewer lumens. Differences in Decipher score were analyzed in a generalized linear model controlling for pathology stage and tumor margin status. A multivariable Cox proportional hazards model was performed for BCR-free survival.

Results

Of 337 cases, 118 were Gleason 3+4=7. The mean Decipher scores in 3+4=7 cases without cribriform, with simple cribriform, and with large cribriform were 0.41, 0.54, and 0.62, respectively. In a multivariable model with pathology stage, margin tumor length, and percentage pattern 4 as covariates, compared to cases without cribriform, simple cribriform was associated with 0.10 increase in Decipher (p=0.03) and 4.7-fold hazard ratio of BCR (95% confidence interval [CI], 0.4-56.5; p=0.22) and large cribriform was associated with 0.17 increase in Decipher (p<0.001) and 16.0-fold hazard ratio of BCR (95% CI, 1.4-181.2; p=0.02).

Conclusions

Among Gleason 3+4=7 carcinomas, large cribriform was associated with higher Decipher scores and greater BCR risk. Our results support that large cribriform is an aggressive pattern 4 subtype and should be considered a contraindication for active surveillance.

Background

Adjuvant therapy plays a major role in treating colorectal cancer, and physicians' views of its effectiveness influence treatment decisions. We assessed physicians' views of the relative benefits and risks of adjuvant chemotherapy and radiotherapy for stages II and III colon and rectal cancers.

Methods

The Cancer Care Outcomes Research and Surveillance Consortium surveyed a geographically dispersed population of medical oncologists, radiation oncologists, and surgeons in the United States about the benefits and risks of adjuvant therapies for colorectal cancer. We used logistic regression to assess the association of physician and practice characteristics with beliefs about adjuvant therapies.

Results

Among 1,296 respondents, > 90% believed the benefits of adjuvant therapies for stage III colorectal cancer outweigh the risks. Only 21.9%, 50%, and 50.4% believed in the net benefit of chemotherapy for stage II colon cancer, chemotherapy for stage II rectal cancer, and radiation for stage II rectal cancer, respectively. Younger physicians were less likely than others to perceive adjuvant therapy for stage II colorectal cancer as beneficial. Medical oncologists were more likely than surgeons and radiation oncologists to endorse the benefits of adjuvant chemotherapy and radiation for stage II rectal cancer, but less likely for stage II colon cancer.

Conclusions

Physicians largely agreed that the benefits of adjuvant chemotherapy for stage III colon cancer, as well as chemotherapy, and radiation for stage III rectal cancer, outweigh the risks, consistent with strong evidence, but were divided over the net benefit of adjuvant therapies for stage II colorectal cancer, where evidence is inconsistent.

Background

Enzalutamide is an antiandrogen used to treat both metastatic and nonmetastatic prostate cancer. Here we present results from a phase 2 trial designed to determine the safety, tolerability, and efficacy of adding enzalutamide to standard androgen deprivation therapy with radiation therapy in high-risk localized or regional, nonmetastatic patients with prostate cancer.

Methods and materials

Enrollment criteria included at least 2 of the following: stage cT3a/b, prostate specific antigen (PSA) ≥20 ng/mL, Gleason grade 8 to 10, ≥33% core involvement on biopsy, or pelvic lymph node involvement on computed tomography or magnetic resonance imaging. Patients with metastatic disease were excluded. All patients received 24 months of leuprolide and enzalutamide, and 5 weeks of intensity modulated radiation therapy followed by a brachytherapy boost. Adverse events (AE), PSA, testosterone, and basic laboratory tests were then followed for up to 36 months. Primary outcomes were safety and tolerability and PSA complete response rate (PSA-CR, defined as PSA ≤0.3). Secondary outcomes included time to biochemical recurrence (BCR; nadir + 2 ng/mL).

Results

Sixteen patients were enrolled; 2 were ineligible and 3 withdrew before starting treatment. Median age at enrollment was 69.0 years (interquartile range [IQR] 11.5). Median treatment duration was 24.0 months (IQR 11.9). Median follow-up time was 35.5 months (IQR 11.2), and 9 of 11 (81.8%) patients completed the 36 months of follow-up. One of 11 (9%) patients had grade 4 AE (seizure), and no grade 5 AE were reported. Four of 11 (36.4%) patients had grade 3 AE, such as erectile dysfunction and hot flashes. All patients achieved PSA-CR, and median time to PSA-CR was 4.2 months (IQR 1.4). At 24 months follow-up, 0 of 11 (0%) patients had a biochemical recurrence. At 36 months, 1 of 9 (11.1%) patient had a biochemical recurrence. Of note, this patient did not complete the full 24 months of enzalutamide and leuprolide due to AEs.

Conclusions

Enzalutamide in combination with standard androgen deprivation therapy and radiation therapy was well-tolerated and effective warranting further study in a randomized controlled trial.

Immune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI. We undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors. We identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03). The presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.

Purpose

In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTVs). Data have emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.

Methods and materials

A literature review was performed abstracting data on nodal recurrence patterns. Data were presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on 3 cases: postoperative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps, which provided a visual assessment of controversial regions, and quantitatively analyzed using Sorensen-Dice similarity coefficients and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity.

Results

Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the postoperative case was 302 cm³, intact node positive case was 409 cm³, and intact node negative case was 342 cm³. Compared with the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the postoperative case was 0.63 (standard deviation [SD] 0.13), the intact node positive case was 0.68 (SD 0.13), and the intact node negative case was 0.66 (SD 0.18). The mean Hausdorff distance (in cm) for the postoperative case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case was 0.33 (SD 0.24). Four regions of CTV controversy were identified, and consensus for each of these areas was reached.

Conclusions

Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international genitourinary radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed.