ASTRO 2024

The 2024 ASTRO annual meeting included a session on prostate cancer, featuring a presentation by Dr. LaToya McLean discussing feasibility, safety, and toxicity of hyaluronic acid rectal spacer in locally recurrent prostate cancer with prior radiation receiving stereotactic body radiotherapy.

(UroToday.com) The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. Anna Dornisch discussing P-CARE, a model to stratify risk of any, metastatic and fatal prostate cancer. Prostate cancer screening is controversial and there are many guideline-based recommendations:
Common tenets of prostate cancer screening guidelines include shared decision-making and individual risk assessment. However, subjective risk assessment based on family history and race is neither accurate nor consistent. A polygenic hazard score based on 290 genomic variants (PHS290; calculated from a single saliva sample) is strongly associated with age at diagnosis of aggressive prostate cancer in large datasets, including the racially and ethnically diverse Million Veteran Program:¹

Moreover, PHS290, ancestry, and family history are each independently associated with lifetime risk of metastatic prostate cancer. At ASTRO 2024, Dr. Dornish and colleagues presented data assessing development and validation of a new integrated model for use in the primary care setting, called Prostate Cancer integrated Risk Evaluation (P-CARE). 

Candidate genetic variants in the literature with reported association with prostate cancer, aggressive prostate cancer, benign prostatic hyperplasia, or benign PSA elevation were considered for inclusion in the new PHS model. The investigators used genetic and phenotypic data from a diverse, population-based cohort (Million Veteran Program, n = 585,418). They then fit a LASSO-regularized PHS model using the age at diagnosis of prostate cancer as the time to event, and all the candidate genetic variants as predictors while covarying the first 5 principal components of genetic ancestry. Next, they combined the new PHS with family history and ancestry to create an integrated risk score, P-CARE, again using age at diagnosis of prostate cancer as time to event. Finally, they estimated the hazard ratio performance of the new PHS model and P-CARE using 10 iterations of a 10-fold cross-validation.  This study found 707 unique candidate variants, of which 601 were ultimately included in the updated polygenic score (PHS601). P-CARE combined PHS601, family history, and agnostic genetic ancestry. Risk stratification with PHS601 for the highest 20% risk (vs the lowest 80% risk) had a hazard ratio for metastatic prostate cancer of 6.69 (95% CI 5.70-7.62):

Risk stratification with P-CARE for the highest 20% risk (vs the lowest 80% risk) had a hazard for metastatic prostate cancer of 6.50 (95% CI 5.50-7.38):
The following shows the cumulative incidence curves, as well as highlighting that those men with high risk, have a 21.2% risk of developing prostate cancer by age 70:
Furthermore, the following shows the cumulative incidence curves, as well as highlighting that those men with high risk, have a 21.2% risk of developing metastatic prostate cancer by age 70:
Dr. Dornisch concluded his presentation discussing P-CARE, a model to stratify risk of any, metastatic and fatal prostate cancer with the following take-home points:

• P-CARE provides a single, objective score that can be used in the primary care setting to stratify patients for risk of meaningful prostate cancer
• The investigators will use P-CARE in a nationwide randomized clinical trial to evaluate precision prostate cancer screening in the VA healthcare system (ProGRESS: The Prostate Cancer, Genetic Risk, and Equitable Screening Study NCT05926102)

Presented by: Anna Dornisch, MD, Radiation Oncologist, UC San Diego, La Jolla, CA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, Washington, DC, Sun, Sept 29 – Wed, Oct 2, 2024.

Reference:

1. Pagadala MS, Lynch J, Karunamuni R, et al. Polygenic risk of any, metastatic, and fatal prostate cancer in the Million Veteran Program. J Natl Cancer Inst. 2023 Feb 8;115(2):190-199.

(UroToday.com) The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. John Nikitas discussing the interplay between acute and late toxicity among patients receiving prostate radiotherapy. Dose escalated external beam radiation therapy is the standard of care for localized prostate cancer, with excellent biochemical control rates. Unfortunately, both acute and late toxicity after prostate radiotherapy arises from normal tissue irradiation at the time of treatment.

The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. Shalini Moningi discussing the examination of the Decipher® prostate genomic classifier in patients with de novo metastatic disease from a large-scale real-world clinical and transcriptomic data linkage. Metastatic prostate cancer is a heterogeneous population, and disease volume and presentation impact patient prognosis:

(UroToday.com) The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. Kosj Yamoah discussing the VANDAAM Study, assessing the impact of Decipher® testing on treatment recommendations in African American and non-African American men with prostate cancer.

(UroToday.com) The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. Yang Song discussing the association with a digital pathology multimodal artificial intelligence (MMAI) algorithm with pro-metastatic genomic pathways in oligometastatic prostate cancer.

(UroToday.com) The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. Philip Sutera discussing validation of a digital pathology-based multimodal artificial intelligence (MMAI) model in oligometastatic castration-sensitive prostate cancer, including patients from the STOMP¹ and ORIOLE² phase II randomized trials.

(UroToday.com The 2024 ASTRO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Anne Hong discussing rectal wall infiltration with a hyaluronic acid-based rectal spacer reversal protocol. Radiation therapy is a mainstay of treatment for prostate cancer, however, treatment may cause gastrointestinal toxicity given that the rectum is an organ at risk. Stabilized hyaluronic acid has recently been approved for use as a rectal spacer and reduces gastrointestinal toxicity in this setting.¹

It has several advantages, including its reversibility using hyaluronidase, which is particularly beneficial in cases of rectal wall infiltration. The use of non-reversible rectal spacers may lead to severe adverse outcomes such as mucosal ulceration, pelvic abscess, and recto-prostatic fistula after rectal wall infiltration. As such, Dr. Hong and colleagues assessed the outcomes of inadvertent rectal wall infiltration by stabilized hyaluronic acid rectal spacers, specifically assessing the feasibility of reversal and gastrointestinal toxicity. 

A total of 16 prostate cancer patients were identified to have rectal wall infiltration after stabilized hyaluronic acid spacer insertion:
The grade of rectal wall infiltration as defined by Fischer Valuck criteria were as follows:³

• Grade 1, n = 5
• Grade 2, n = 6
• Grade 3, n = 5

The median volume of misplaced stabilized hyaluronic acid was 2.8 cc from an average total of 9 cc used. No post-procedural gastrointestinal symptoms were reported, and digital rectal examination did not detect abnormalities in any patients. A sigmoidoscopy was performed in 12 patients including all 5 with grade 3 rectal wall infiltration, and all of these showed intact rectal mucosa:
Seven patients underwent targeted reversal procedures while 9 patients were monitored. The Fischer Valuck grading and reversal did not demonstrate an association (Chi-squared test, p = 0.41). Of those who underwent reversal procedures, the median volume of misplaced hyaluronic acid is 4 mL (mean 3.8 mL), compared to 1.5 mL (mean 2.1 mL) in those who did not undergo reversal (Mann-Whitney U test, p = 0.10). All 7 patients who underwent reversal with hyaluronidase were successful, and no post-reversal complications were reported.

One patient underwent successful reinsertion of stabilized hyaluronic acid following reversal. During the reinsertion procedure, hydro dissection using normal saline was performed before stabilized hyaluronic acid placement to ensure positioning within the perirectal fact. The proceduralist rated the re-insertion as “easy” and a subsequent pelvic MRI confirmed the stabilized hyaluronic acid was correctly placed before initiation of radiotherapy. Initiation of radiation therapy was delayed in 11 cases by a median of 8 weeks. Of the cases where radiation therapy was not delayed, the rectal wall infiltration volume ranged from 0.5 mL to 2 mL. During delayed radiation therapy, ADT was continued and all patients completed their radiotherapy as planned. On follow-up, acute rectal toxicity was experienced by four patients. Using the CTCAE score, two patients experienced grade 1 rectal toxicity, and two patients experienced grade 2 rectal toxicity.

Dr. Hong concluded her presentation discussing rectal wall infiltration with a hyaluronic acid-based rectal spacer reversal protocol with the following take-home points:

• Stabilized hyaluronic acid is increasingly used as a rectal spacer to reduce radiation-related gastrointestinal side effects in prostate cancer treatment
• Rectal wall infiltration is uncommon but a potentially serious complication. However, rectal wall infiltration can be safely managed using either observation or reversal. While surgical removal remains an option, it was not required in this study
• Additional key messages:
  • Sigmoidoscopy may not be routinely required if the patient is asymptomatic and digital rectal examination is normal
  • The decision to reverse a rectal wall infiltration is dependent on patient symptoms, clinical assessment, and volume of rectal wall infiltration.
  • It is possible to reinsert stabilized hyaluronic acid after a reversal procedure.

Presented by: Anne Hong, MD, Urology Research Fellow, Austin Health, Melbourne, Victoria, Australia

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, Washington, DC, Sun, Sept 29 – Wed, Oct 2, 2024.

References:

1. Mariados NF, Orio 3^rd PF, Schiffman Z, et al. Hyaluronic acid spacer for hypofractionated prostate radiation therapy: A randomized clinical trial. JAMA Oncol. 2023 Apr 1;9(4):511-518.
2. Hong A, Ischia J, Chao M. Case report: Reversal of hyaluronic acid rectal wall infiltration with hyaluronidase. Front Oncol. 2022;12:870388
3. Fischer-Valuck BW, Chundury A, Gay H, et al. Hydrogen spacer distribution within the perirectal space in patients undergoing radiotherapy for prostate cancer: Impact of spacer symmetry on rectal dose reduction and the clinical consequences of hydrogel infiltration into the rectal wall. Pract Radiat Oncol. 2017 May-Jun;7(3):195-202.

(UroToday.com) The 2024 ASTRO annual meeting included a session on prostate cancer, featuring a presentation by Yuan-Hong Lin discussing the impact of hyaluronic acid rectal spacer quality score and Fisher-Valuck spacer symmetry score on rectal dosimetry and acute and late gastrointestinal toxicity outcomes. Moderately hypofractionated radiotherapy to the prostate is now the standard of care for management of localized prostate cancer. However, a prior meta-analysis demonstrated a 9.1% greater absolute risk of >= grade 2 acute gastrointestinal toxicity compared to conventionally fractionated radiotherapy.¹

(UroToday.com) The 2024 ASTRO annual meeting included a session on optimizing the therapeutic ratio in prostate cancer, featuring a presentation by Dr. Andre Gouveia discussing early results of PBS, a phase II trial assessing stereotactic body radiotherapy versus conventional fractionation external beam radiotherapy boost for unfavorable intermediate and high-risk prostate cancer.

(UroToday.com) The 2024 ASTRO annual meeting included a session on optimizing the therapeutic ratio in prostate cancer, featuring a presentation by Dr. Carlton Johnny discussing focal MR-guided HDR brachytherapy boost combined with stereotactic body radiotherapy for localized prostate cancer. The objective of this study was to describe a population of patients who may benefit from focal dose escalation with early outcome measures.

(UroToday.com) The 2024 ASTRO annual meeting included a session on optimizing the therapeutic ratio in prostate cancer, featuring a presentation by Dr. Abhishek Solanki discussing the initial results of F-SHARP, a multi-institutional phase 1/2 trial of focal dose-escalated salvage high dose rate (HDR) brachytherapy for radiorecurrent prostate cancer.

(UroToday.com) The 2024 ASTRO annual meeting included a session on optimizing the therapeutic ratio in prostate cancer, featuring a presentation by Dr. Vishal Dhere discussing volumetric changes and acute toxicity with ⁶⁸Ga PSMA PET/CT versus ¹⁸F-Fluciclovine PET/CT guided post-prostatectomy radiation from the EMPIRE-2 trial.

(UroToday.com) The 2024 ASTRO annual meeting included a session on optimizing the therapeutic ratio in prostate cancer, featuring a presentation by Dr. Amar Kishan discussing two-year outcomes from the MIRAGE randomized clinical trial. Dr. Kishan started his presentation by highlighting that planned target volume accounts for possible uncertainties in beam alignment, patient positioning, organ motion, and organ deformation.

(UroToday.com) The 2024 ASTRO annual meeting included a session on optimizing the therapeutic ratio in prostate cancer, featuring a presentation by Dr. William Hall discussing dose-escalated pelvic lymph node Intensity-Modulated Radiation Therapy (IMRT) with a simultaneous hypofractionated boost to the prostate for NCCN very-high-risk prostate cancer.

 The 2024 ASTRO annual meeting included a session on the management of small cell neuroendocrine tumors of the genitourinary tract, featuring a presentation by Dr. Jean Hoffman-Censits discussing emerging systemic therapy and clinical trials. Dr. Hoffman-Censits notes that small-cell bladder and prostate cancer patients are typically excluded from clinical trials due to their aggressive biology and clinical behavior.

(UroToday.com) The 2024 ASTRO annual meeting included a late-breaking abstract session, featuring a presentation by Dr. Ana Kiess discussing outcomes of the RAVENS phase 2 randomized trial assessing outcomes of radium-223 + stereotactic ablative radiotherapy versus stereotactic ablative radiotherapy alone for oligometastatic prostate cancer. Previously, the STOMP¹ and ORIOLE² randomized clinical trials showed progression-free survival benefits of metastasis-directed therapy alone without ADT for oligometastatic hormone-sensitive prostate cancer:
However, most patients (~86%) with bone metastatic oligometastatic hormone-sensitive prostate cancer recur with additional bone metastases following metastasis-directed therapy alone:
Dr. Kiess and colleagues hypothesized that the addition of bone metastatic-targeting alpha-emitter radium-223, approved for treatment of bone metastases castration-resistant prostate cancer (mCRPC)³ showing an improvement in overall survival for radium-223 versus placebo (14.9 versus 11.3 months), could delay progression of disease. Moreover, at ESMO 2024, Silke Gillessen presented data from PEACE-3 showing that radium-223 in combination with enzalutamide for first-line mCRPC improved overall survival over enzalutamide alone (HR 0.69, 95% CI 0.52-0.90). In addition, biomarkers to determine patients who benefit most from metastasis-directed therapy are still poorly defined. At ASTRO 2024, Dr. Kiess reported on the first randomized clinical trial to examine radium-223 and evaluate novel biomarkers in bone metastatic oligometastatic hormone-sensitive prostate cancer. 

 In this phase 2 multi-institutional randomized clinical trial (NCT04037358), men with recurrent oligometastatic hormone-sensitive prostate cancer (>1 bone metastases & <5 radiation fields) were stratified by institution, primary management (radiotherapy vs surgery), PSA doubling time and prior ADT, and subsequently randomized 1:1 to stereotactic ablative radiation metastasis-directed therapy or stereotactic ablative radiation and 6 monthly cycles of radium-223. The trial schema for RAVENS is as follows:
 

The primary endpoint was composite progression-free survival:

• >= 25% PSA increase and >= nadir + 2 ng/mL and/or
• Radiological progression by RECIST 1.1 or new lesion on bone scan and/or
• Symptomatic progression (worsening disease-related symptoms or new cancer-related complications) and/or
• ADT initiation or death due to any cause 

Secondary endpoints included:

• ADT free survival
• Metastasis free survival
• Overall survival
• Patterns of progression
• Toxicity and quality of life
• Molecular studies: germline and somatic DNA sequencing, circulating tumor cells, T-cell receptor sequencing, proteomics, and ctDNA sequencing using CAPP-Seq

Tissue, liquid, and imaging correlative studies were obtained and analyzed as biomarkers. 

From August 2019 – March 2023, 64 patients were randomized: 33 to stereotactic ablative radiation and 31 to stereotactic ablative radiation/radium-223. The arms were balanced for key covariates and 26 (87%) patients received the full 6 planned cycles of radium-223:

Over a median follow-up of 18.7 months, the median progression-free survival was 11.8 months with stereotactic ablative radiation and 10.5 months with stereotactic ablative radiation/radium-223 (stratified HR 1.37, 95% CI, 0.78-2.39, p = 0.27):

Additionally, there was no difference between arms with regard to metastasis-free survival and ADT-free survival:
Dr. Keiss notes that perhaps one of the reasons radium-223 did not work in oligometastatic disease is due to the mechanism of action in that radium-223 is likely most effective in higher volume disease with bone lesions not eradicated by stereotactic ablative radiotherapy. In a dosimetry/treatment optimization sub-study of RAVENS, SPECT imaging demonstrated tumor uptake based on 5 patients imaged at 2, 24, and 48 hours after cycle 1 and cycle 6:

Overall, 7 patients experienced grade 3 toxicity (no grade 4 or 5), of which lymphopenia was the most common. There were more grade 1-2 hematologic and gastrointestinal toxicities related to radium-223 + stereotactic ablative radiotherapy:

A high-risk genomic signature, noting pathogenic mutations in ATM, BRCA1, BRCA2, RB1, or TP53 was previously assessed in STOMP and ORIOLE, showing the largest benefit of metastasis-directed therapy in patients with high-risk mutations. In RAVENS, this high-risk genomic signature was validated in 23 patients, which was prognostic for progression-free survival (median 12.5 months for low-risk versus 6.5 months for high-risk); HR 5.95, 95% CI 1.83-19.3:

T-cell receptor samples were available at baseline (44/63, 70%), at 90 days of follow-up (42/63, 67%), and with paired samples (37/63, 59%). Greater unique productive T-cell receptor rearrangements were prognostic for progression-free survival independent of treatment arm (adjusted HR 0.45, 95% CI, 0.21-0.96; p = 0.04):

Additionally, unique productive T-cell receptor rearrangements were reduced with radium-223 + stereotactic ablative radiotherapy, but not in stereotactic ablative radiotherapy alone:

Finally, Dr. Keiss showed that T-cell receptor clonal expansion still occurs after stereotactic ablative radiotherapy with or without radium-223: 
Dr. Keiss concluded her presentation discussing outcomes of the RAVENS phase 2 randomized trial with the following take-home points:

• Stereotactic ablative radiotherapy alone for oligometastatic hormone-sensitive prostate cancer affords progression-free survival benefits, but emergence of additional bone metastases in most patients remains a challenge
• This is the first report noting that the addition of radium-223 to stereotactic ablative radiotherapy metastasis-directed therapy in this low-volume bone metastatic state does not delay progression of disease
• This trial validates the T-cell receptor repertoire as a prognostic biomarker in oligometastatic hormone-sensitive prostate cancer treated with stereotactic ablative radiotherapy metastasis-directed therapy
• These results underline the importance of randomized clinical trials in oligometastatic hormone-sensitive prostate cancer with concurrent collection of biological correlates

Presented by: Ana Kiess, MD, PhD, Radiation Oncologist, Johns Hopkins University, Baltimore, MD

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, Washington, DC, Sun, Sept 29 – Wed, Oct 2, 2024.

References:

1. Ost P, Reynders D, Decaestecker K, et al. Surveillance of metastasis-directed therapy for oligometastatic cancer recurrence: A prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018 Feb 10;36(5):446-453.
2. Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol 2020 Mar 26;6(5):650-659.
3. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369(3):213-223.

(UroToday.com) The 2024 ASTRO annual meeting included a session on the management of small-cell neuroendocrine tumors of the genitourinary tract, featuring a presentation by Dr. Nima Almassi discussing the role of surgery in the management of genitourinary small-cell tumors.

(UroToday.com) The 2024 ASTRO annual meeting included a session on the management of small-cell neuroendocrine tumors of the genitourinary tract, featuring a presentation by Dr. Emily Weg discussing the role of radiation therapy for small-cell neuroendocrine tumors of the genitourinary tract. Dr. Weg notes that primary small cell carcinoma of the prostate has an incidence of <1%, with >25% of patients presenting with a PSA < 4 ng/mL.

(UroToday.com) The 2024 ASTRO annual meeting included a session on the management of small cell neuroendocrine tumors of the genitourinary tract, featuring a presentation by Dr. Vedang Murthy discussing radiation therapy for small cell bladder cancers. Dr. Murthy started with a clinical case of a 53-year-old female who underwent a TURBT that showed 95% small cell carcinoma histology and 5% urothelial. The staging CT scan is as follows, confirming T3N1M0 small cell carcinoma of the bladder:
The first question with regards to treatment decisions is whether neoadjuvant chemotherapy is appropriate for this patient. A historical series at MD Anderson Cancer Center from 2004 notes that among 46 patients, neoadjuvant chemotherapy followed by surgery improved survival compared to surgery alone. A follow-up of this series in 2013 showed that among 172 patients, neoadjuvant chemotherapy followed by surgery improved survival compared to adjuvant chemotherapy or no chemotherapy.

Dr. Murthy notes that the clinical guidelines agree that neoadjuvant chemotherapy is preferred over adjuvant chemotherapy:

1. EAU: “Bladder urothelial carcinoma with small cell neuroendocrine variant should be treated with neoadjuvant chemotherapy followed by consolidating local therapy”
2. AUA/ASCO/ASTRO/SUO: “For histologic subtypes, neoadjuvant chemotherapy is preferred over adjuvant chemotherapy”

The patient in the aforementioned case did undergo neoadjuvant chemotherapy with 3 cycles of cisplatin + etoposide, with a complete response to the primary lesion:

The second question in a treatment decision is whether or not local therapy is needed. Both an NCDB and Memorial Sloan Kettering Cancer Center showed that chemotherapy + local therapy is better than chemotherapy alone:

The third question in a treatment decision is what type of local treatment should we choose? Surgery or radiotherapy? Based on limited retrospective evidence, a study from the UK (n = 61 for radical cystectomy vs n = 104 for radiotherapy) and a study from Canada (n = 33 for trimodality therapy vs n = 44 for radical cystectomy) showed that essentially radiotherapy and radical cystectomy are likely equivalent with regards to local therapy in neuroendocrine bladder cancer:

Additionally, an NCDB study from 2020 [1] looked at outcomes among patients with variant muscle-invasive bladder cancer to better assess the role of bladder-preserving chemoradiotherapy versus radical cystectomy.¹ Among 356 patients that had bladder-preserving chemoradiotherapy and 2,093 patients that had radical cystectomy, using propensity score weighted analysis, there was no statistical significant difference in overall survival for patients with bladder-preserving chemoradiotherapy as compared to cystectomy (p = 0.387). Additionally, for neuroendocrine, micropapillary, or not otherwise specified histology subgroups, there was no significant difference:

However, patients with adenocarcinoma (HR 1.75) or squamous cell carcinoma (HR 1.49) had worse overall survival associated with bladder-preserving chemoradiotherapy compared to radical cystectomy.

For those that choose radiotherapy, the next question with regards to a treatment decision is what is the volume, dose, fractionation schedule for treatment, and whether prophylactic cranial irradiation should be used? For radiotherapy volume, specifically whole bladder versus partial (tumor/bed), Dr. Murthy notes that there is no definitive data, but studies assessing radical versus partial cystectomy for these patients suggest no difference in cancer-specific survival for bladder neuroendocrine carcinoma, thus both options seem reasonable. Should we treat the pelvis electively? The rationale is that this is an avenue for systemic metastasis, and IMRT with IG-ART allows safe treatment. In a recent study by Halstuch et al. [2] assessing survival outcomes of pure urothelial to histologic subtypes of urothelial carcinoma after radiotherapy, they found the following for radiotherapy to the bladder only versus whole pelvis with regards to metastasis-free survival, cancer-specific survival, and overall survival. 

Can we provide these patients with hypofractionated radiotherapy? Dr. Murthy notes that in an individual patient data meta-analysis of the BC2001 and BCON trials,³ over a median follow-up of 120 months (IQR 99-159), patients who received 55 Gy in 20 fractions had a lower risk of invasive locoregional recurrence than those who received 64 Gy in 32 fractions (adjusted HR 0.71, 95% CI 0.52-0.96). Additionally, both schedules had similar toxicity profiles (adjusted RD -3.37%, 95% CI -11.85 to 5.10):

Finally, should we consider prophylactic cranial irradiation? Dr. Murthy notes that for a patient with >= T3bN+M1 neuroendocrine carcinoma of the bladder, there is a brain metastasis risk of ~50%. Presented at ASCO GU 2022, Choi and colleagues noted that among 24 patients with bulky, high stage small cell urothelial cancer, the risk of brain metastases decreased from ~50% to 14% after prophylactic cranial irradiation (24 Gy/10 fractions).

Dr. Murthy concluded his presentation discussing radiation therapy for small cell bladder cancers with the following key takeaways for providing treatment options for these patients:
Presented by: Vedang Murthy, MD, DNB, DipEPP, Professor and Radiation Oncologist, Tata Memorial Centre, New Mumbai, Maharashtra, India

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, Washington, DC, Sun, Sept 29 – Wed, Oct 2, 2024.

References:

1. Janopaul-Naylor JR, Zhong J, Liu Y, et al. Bladder preserving chemoradiotherapy compared to surgery for variants of urothelial carcinoma and other tumor types involving the bladder: An analysis of the National Cancer Database. Clin Transl Radiat Oncol. 2020 Nov 9;26:30-34.
2. Halstuch D, Kool R, Marcq G, et al. The Impact of Histologic Subtypes on Clinical Outcomes After Radiation-Based Therapy for Muscle-Invasive Bladder Cancer. J Urol. 2024 Jul 25 [Epub ahead of print].
3. Choudhury A, Porta N, Hall E, et al. Hypofractionated radiotherapy in locally advanced bladder cancer: An individual patient data meta-analysis of the BC2001 and BCON trials. Lancet Oncol. 2021 Feb;22(2):246-255.