ASCO 2024

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer, and a presentation by Dr. Philip Sutera discussing the validation of a digital pathology-based multimodal artificial intelligence model in oligometastatic castration-sensitive prostate cancer (CSPC). Oligometastatic CSPC is a state of limited metastatic disease, and randomized trials have demonstrated improvements in progression-free survival in patients with oligometastatic CSPC treated with metastasis-directed therapy. However, clinical outcomes remain heterogeneous and response to metastasis-directed therapy is variable, raising the need for prognostic/predictive biomarkers. A multimodal artificial intelligence biomarker (ArteraAI Prostate Test) was recently trained using data from patients with localized prostate cancer and found to be prognostic.^1,2 The multimodal architecture is composed of two parts: (i) a tower stack to parse a variable number of digital histopathology slides, and (ii) another tower stack to merge the resultant features and predict binary outcomes:

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31 and June 4 was host to the Session: Managing Variant Histologies in Urothelial and Renal Cell Cancers. Dr. Sumanta Kumar Pal discussed What Is Variant Histology Renal Cell Cancer and What Are the Available Treatment Options to date.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31 and June 4 was host to the Session: Managing Variant Histologies in Urothelial and Renal Cell Cancers. Dr. Jean Hoffman-Censits delve into what is considered variant Histology urothelial cancer and what are the available treatment options in 2024.

The landscape of first-line management for urothelial cancer has radically changed over the past year and continues to evolve. With the approval of new agents like enfortumab vedotin (EV) combined with pembrolizumab, as well as new regimens such as nivolumab and gemcitabine cisplatin (GC), there are now a variety of options for treating patients with urothelial cancer (UC).(1,2) However, the majority of trials leading to these changes and updates in clinical practice have predominantly included patients with pure UC. A major limitation of these trials is that they often lump variant histology (VH) into a single category rather than splitting outcomes data into different variants. This approach assumes that "variant histology" is a single entity, ignoring the fact that many variants exist, each with distinct prognoses, outcomes, and responses to platinum-based chemotherapy or immunotherapy.

The most common VH is squamous cell carcinoma, which was found to represent 31% of VH in a recent report on the distribution of histologic subtypes of bladder cancer. This was followed by neuroendocrine (17%), adenocarcinoma and sarcomatoid variants (16%), with the least common being plasmacytoid.(3)

After the presentation of the EV-302 study at ESMO 2023, the frontline therapy for locally advanced unresectable or advanced UC has shifted to EV + pembrolizumab. Ideally, patients who progress after this first line should transition to GC. (2) Another frontline treatment option is nivolumab + GC, as reported in the CheckMate 901 trial. (1) Additional options for patients after progression include erdafitinib, sacituzumab govitecan, and trastuzumab deruxtecan. However, given the numerous available options and tools for improving patient selection, it remains challenging to determine the optimal choice for the first-line setting and after progression.

There are many different variants considered VH for UC. Dr. Hoffman-Censits delved into each one of them separately, which we will discuss below.

Small cell cancer is typically an aggressive tumor, but it often responds well to chemotherapy. Brain involvement is frequently seen at presentation, and recurrence rates are high. The treatment for this histologic variant has been extrapolated from data on small cell lung cancer (SCLC). Etoposide (EP) neoadjuvant chemotherapy (NAC) has been recommended, even for tumors staged as cT1. It has been shown that NAC followed by local treatment improves survival outcomes compared to radical cystectomy (RC) alone. However, any residual small cell cancer at the RC pathology is associated with worse outcomes than residual UC alone. (4)

Data supporting immune checkpoint inhibitors for small cell cancer has been published. However, the preferred approach remains NAC followed by surgery and possibly adjuvant nivolumab. With our current treatment paradigm of using upfront EV + Pembrolizumab for the frontline setting of UC, this approach could be considered and discussed for patients with small cell cancer according to Dr. Hoffman-Censits.

Three clinical trials examining treatment options for the small cell variant are ongoing:

• In the neoadjuvant setting, a trial exploring Atezolizumab with Platinum and Etoposide Chemotherapy Followed by Cystectomy for Patients with Localized Small Cell Neuroendocrine Bladder Cancer (NCT05312671).
• In the first-line setting of advanced extrapulmonary neuroendocrine tumors, a phase II/III trial (NCT05058651) compares the effect of atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone.
• In the second-line setting, the LASER trial (NCT06228066) is evaluating Lurbinectedin with or without Avelumab in small cell carcinoma of the bladder.

Sarcomatoid differentiated variant histology of urothelial carcinoma (UC) is characterized by malignant spindle cells with a nonspecific morphologic appearance. Retrospective studies generally do not show a significant benefit from NAC or adjuvant chemotherapy (AC), but the receptivity in these studies is low. (5) However, a pooled analysis indicates that NAC can improve overall survival (OS). (6) One specific NAC regimen—cisplatin (35 mg/m²), gemcitabine (800 mg/m²), and docetaxel (35 mg/m²) on days 1 and 8, with G-CSF support every 21 days for four cycles—followed by radical cystectomy (RC) has shown promising results, with a ypCR rate of 38% and a <ypT2 rate of 50%. Additionally, sarcomatoid UC often exhibits high PD-L1 expression, with an overall response rate (ORR) of 35-50% to immune checkpoint inhibitors (ICI) in the first-line setting.

Squamous cell carcinoma (SCC) of the urothelial tract is an aggressive variant that can present as locally advanced disease often. One of the notable clinical features is hypercalcemia, which requires careful monitoring of the metabolic panel. Histologically, SCC exhibits keratinization and intercellular bridges, making it indistinguishable from squamous carcinoma of other primary sites.

In a prospective study involving ifosfamide, paclitaxel, and cisplatin, the overall response rate (ORR) was 25% in eight patients with SCC. Data from the SEER database (n=1371) indicates a survival benefit with adjuvant chemotherapy. (7)

SCC shows poorer progression-free survival (PFS) and overall survival (OS) compared to conventional urothelial carcinoma (UC). Specifically, PFS for SCC treated with cisplatin and paclitaxel (CP) was 1.9 months versus 4.8 months for UC (P < .01), and median OS was 9.2 months for SCC compared to 20.7 months for UC (P < .01). Additionally, SCC has a lower ORR to enfortumab vedotin (EV) or EV plus pembrolizumab (EV+P), at 17% versus 70% for UC (P < .01), with a median PFS of 3.4 months for SCC compared to 15.8 months for UC (P < .01). (3)

The micropapillary variant of urothelial carcinoma is characterized by HER2 activating alterations. This molecular feature makes it a potential candidate for targeted therapies. In the DESTINY-PanTumor02 Phase II trial, trastuzumab deruxtecan was evaluated in 41 patients with previously treated bladder cancer, including those with micropapillary histology. The overall response rate (ORR) was 56.3% in tumors with IHC3+ HER2 expression and 35% in tumors with IHC2+ expression. These findings highlight the efficacy of HER2-targeted therapy in this aggressive variant and support its use in clinical practice for patients with HER2-positive micropapillary urothelial carcinoma. (8)

Urachal cancer is a rare malignancy accounting for <1% of bladder cancers. This is an aggressive disease with the overall survival for recurrent or metastatic disease currently less than two years. Highlighted at ASCO 2024 was a prospective study (ULTMA; KCSG GU20-03) assessing modified FOLFIRINOX in 21 patients treated between 2021 and 2023. The ORR was 61.9%, with complete responses (CR) in 2 patients (9.5%), partial responses (PR) in 11 patients (52.4%), and stable disease (SD) in 8 patients (38.1%). Progression-free survival (PFS) was 9.3 months, and overall survival (OS) was 19.7 months. (9) Additionally, the MD Anderson Cancer Center (MDACC) retrospective experience presented at ASCO GU 2024 reviewed outcomes with the GemFLP regimen (Gemcitabine, 5-FU, and cisplatin) in 40 patients with urachal cancer, further supporting the efficacy of tailored chemotherapy approaches for this rare and aggressive variant. (10)

Dr. Hoffman-Censits discussed the application of EV for variant histology urothelial carcinoma , noting that while the population of patients with variant histology was reported in published trials, the response of variant histology to EV was not consistently reported. She highlighted two ongoing studies with immune checkpoint inhibitors (IO) in this context: "Enfortumab vedotin plus pembrolizumab in the treatment of locally advanced or metastatic bladder cancer of variant histology: A phase II study (NCT05756569)" and "A phase II multicenter study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors (E-VIRTUE) (NCT06041503) that hopefully would give us some answers into this the treatment of this rare variants.

The UNITE study, a large retrospective cohort, assessing the efficacy of EV in advanced UC including variant histology, included a total of 260 patients treated with EV monotherapy. (n=70), 66 patients with UC and variant histology, and 4 with pure variant histology. The ORR in variant histology was 42% compared to 58% in patients with pure UC (n=142), this was not significant (p=0.056). A detailed response according to different variant histology groups is shown in the table below. (11)

Furthermore, the median OS in pure UC was 14.8 months, compared to 13.4 months (p=0.064) in patients treated with EV monotherapy.

Dr. Hoffman-Censits presented updated outcomes from the UNITE study, now encompassing a total of 566 patients, including 200 with variant histology. Among these, UC predominant tumors (n=151), those with ≥50% variant histology (n=35), and pure variant histology cases (n=14) were analyzed. The study revealed a 0% ORR in pure variant histology, regardless of subtype (0/5 SCC, 0/3 PC, 0/1 Sarc, 0/2 Small Cell), as well as no response observed with any small cell component, irrespective of percentage.

In the UNITE study, outcomes were evaluated for 116 patients treated with Sacituzumab Govitecan, with 44 of them having variant histology. The overall response rate (ORR) for all patients was 24%, comparable to 23% for those with any variant histology. When analyzed based on specific VH groups, the results are detailed in the table below.

SMART is an open-label, non-randomized Phase 2 trial designed to evaluate treatment outcomes in patients with locally advanced (unresectable) or metastatic genitourinary (GU) tumors of specific histologies, including small cell carcinoma, squamous cell carcinoma, primary adenocarcinoma of the bladder or urinary tract, renal medullary carcinoma (RMC), or squamous cell carcinoma of the penis. Patients will receive Sacituzumab Govitecan (SG) or SG and concomitant atezolizumab, results are awaited. (11)

Of note, the CheckMate 901 study included a significant proportion of patients with variant histology, comprising 51% in the Nivolumab + GC arm and 53% in the GC arm. However, the outcomes for this specific population have not yet been reported. (1)

With our new treatment paradigms, patients with variant histology in 2024 should be approached carefully. Dr. Hoffman-Censits suggests initiating treatment with platinum-based chemotherapy. For those with biomarker-positive tumors, she advocates for prioritizing other drugs as the initial treatment option.

These are the key takeaways Dr. Hoffman-Censits used to conclude her presentation:

• Prospective trials face challenges in funding and accrual, requiring larger sample sizes for meaningful results.
• Basket studies offer opportunities but have limited capacity for extensive clinical development.
• Reporting practices of variant histology in large prospective studies vary, potentially impacting data interpretation.
• Historical practices of excluding subtypes/women/African American may have contributed to the perception of bladder cancer as predominantly affecting white males, highlighting the need for more inclusive trial design.
• There are now two potent frontline regimens available for bladder cancer, raising questions about how to maximize their combined benefits.
• Biomarker-selected and unselected agents approved for second-line use in urothelial carcinoma (UC) provide an expanding toolkit for treating non-UC subtypes.
• Biopsying at disease progression is recommended to inform treatment sequencing and target specific subtypes, particularly in variant histologies.
• The "rainbow" of available treatments presents challenges for FDA approval in data-scarce areas like micropapillary and small cell carcinoma.

Presented By: Jean H. Hoffman-Censits, MD, Genitourinary medical oncologist at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and The Greenberg Bladder Cancer Institute at Johns Hopkins.

Written By: Julian Chavarriaga, MD – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31^st and June 4^th.

References:

1. van der Heijden MS, Sonpavde G, Powles T, Necchi A, Burotto M, Schenker M, Sade JP, Bamias A, Beuzeboc P, Bedke J, Oldenburg J, Chatta G, Ürün Y, Ye D, He Z, Valderrama BP, Ku JH, Tomita Y, Filian J, Wang L, Purcea D, Patel MY, Nasroulah F, Galsky MD; CheckMate 901 Trial Investigators. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2023 Nov 9;389(19):1778-1789. doi: 10.1056/NEJMoa2309863. Epub 2023 Oct 22. PMID: 37870949.
2. Powles T, Valderrama BP, Gupta S, Bedke J, Kikuchi E, Hoffman-Censits J, Iyer G, Vulsteke C, Park SH, Shin SJ, Castellano D, Fornarini G, Li JR, Gümüş M, Mar N, Loriot Y, Fléchon A, Duran I, Drakaki A, Narayanan S, Yu X, Gorla S, Homet Moreno B, van der Heijden MS; EV-302 Trial Investigators. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer. N Engl J Med. 2024 Mar 7;390(10):875-888. doi: 10.1056/NEJMoa2312117. PMID: 38446675
3. Koehne EL, Bakaloudi DR, Ghali F, Nyame Y, Schade GR, Grivas P, Yezefski TA, Hawley JE, Yu EY, Hsieh AC, Montgomery RB, Psutka SP, Gore JL, Wright JL. Adjuvant Chemotherapy and Survival After Radical Cystectomy in Histologic Subtype Bladder Cancer. Clin Genitourin Cancer. 2024 Apr 25:102100. doi: 10.1016/j.clgc.2024.102100. Epub ahead of print. PMID: 38763862.
4. Hoffman-Censits J, Choi W, Pal S, Trabulsi E, Kelly WK, Hahn NM, McConkey D, Comperat E, Matoso A, Cussenot O, Cancel-Tassin G, Fong MHY, Ross J, Madison R, Ali S. Urothelial Cancers with Small Cell Variant Histology Have Confirmed High Tumor Mutational Burden, Frequent TP53 and RB Mutations, and a Unique Gene Expression Profile. Eur Urol Oncol. 2021 Apr;4(2):297-300. doi: 10.1016/j.euo.2019.12.002. Epub 2020 Feb 13. PMID: 32061548.
5. Vetterlein MW, Wankowicz SAM, Seisen T, Lander R, Löppenberg B, Chun FK, Menon M, Sun M, Barletta JA, Choueiri TK, Bellmunt J, Trinh QD, Preston MA. Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology. Cancer. 2017 Nov 15;123(22):4346-4355. doi: 10.1002/cncr.30907. Epub 2017 Jul 25. PMID: 28743155.
6. Almassi N, Vertosick EA, Sjoberg DD, Wong NC, Huang C, Pietzak EJ, Cha EK, Donahue TF, Dalbagni G, Bochner BH, Iyer G, Rosenberg JE, Bajorin DF, Al-Ahmadie H, Goh AC. Pathological and oncological outcomes in patients with sarcomatoid differentiation undergoing cystectomy. BJU Int. 2022 Apr;129(4):463-469. doi: 10.1111/bju.15428. Epub 2021 May 24. PMID: 33866683; PMCID: PMC8522172.
7. Abdel-Rahman O. Squamous Cell Carcinoma of the Bladder: A SEER Database Analysis. Clin Genitourin Cancer. 2017 Jun;15(3):e463-e468. doi: 10.1016/j.clgc.2016.10.007. Epub 2016 Oct 28. PMID: 27876505.
8. Meric-Bernstam F, Makker V, Oaknin A, Oh DY, Banerjee S, González-Martín A, Jung KH, Ługowska I, Manso L, Manzano A, Melichar B, Siena S, Stroyakovskiy D, Fielding A, Ma Y, Puvvada S, Shire N, Lee JY. Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial. J Clin Oncol. 2024 Jan 1;42(1):47-58. doi: 10.1200/JCO.23.02005. Epub 2023 Oct 23. PMID: 37870536; PMCID: PMC10730032.
9. Lee, JL et al A multicenter phase II study of modified FOLFIRINOX for first-line treatment for advancedurachal cancer (ULTMA; KCSG GU20-03).J Clin Oncol 42, 2024 (suppl 16; abstr 4510)
10. Moussa MJ et al. Clinical outcomes of frontline GemFLP in advanced urachal and non-urachal adenocarcinomas of the urinary tract: The MD Anderson Cancer Center (MDACC) experience. J Clin Oncol Abstr 630
11. Koshkin VS, Henderson N, James M, Natesan D, Freeman D, Nizam A, Su CT, Khaki AR, Osterman CK, Glover MJ, Chiang R, Makrakis D, Talukder R, Lemke E, Olsen TA, Jain J, Jang A, Ali A, Jindal T, Chou J, Friedlander TW, Hoimes C, Basu A, Zakharia Y, Barata PC, Bilen MA, Emamekhoo H, Davis NB, Shah SA, Milowsky MI, Gupta S, Campbell MT, Grivas P, Sonpavde GP, Kilari D, Alva AS. Efficacy of enfortumab vedotin in advanced urothelial cancer: Analysis from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study. Cancer. 2022 Mar 15;128(6):1194-1205. doi: 10.1002/cncr.34057. Epub 2021 Dec 9. PMID: 34882781.
12. Andre Rashad Kydd et al.SMART: A phase II study of sacituzumab govitecan (SG) with or without atezolizumab immunotherapy in rare genitourinary (GU) tumors such as small cell, adenocarcinoma, and squamous cell bladder/urinary tract cancer, renal medullary carcinoma (RMC) and penile cancer.. JCO 42, TPS4627-TPS4627(2024).DOI:10.1200/JCO.2024.42.16_suppl.TPS4627

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on applications of artificial intelligence in prostate cancer care, and a presentation by Dr. Irbaz B. Riaz discussing the use of artificial intelligence to optimize systemic therapy for prostate cancer. Dr. Bin Riaz started by highlighting the following definitions:

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on applications of artificial intelligence in prostate cancer care, and a presentation by Dr. Liang Cheng discussing artificial intelligence and deep learning in prostate cancer pathology. Dr. Cheng started this presentation by noting that the recently published Lancet Commission on Prostate Cancer highlights several sobering statistics:¹

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on applications of artificial intelligence in prostate cancer care, and a presentation by Dr. Stephanie Harmon discussing innovation and potential for diagnostic imaging in prostate cancer. There are many opportunities for artificial intelligence in prostate imaging, including:

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on bladder cancer, and a presentation by Dr. Yijun Shen discussing results of a phase 2 trial of intravesical camrelizumab in BCG-unresponsive high-risk non-muscle invasive bladder cancer. In a phase I study, intravesical camrelizumab (at a maximum tolerated dose of 200 mg) was well tolerated by patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer. This phase II trial aimed to assess the efficacy and safety of intravesical camrelizumab at the established phase I maximum tolerated dose.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on bladder cancer, and a presentation by Dr. Arlene Siefker-Radtke discussing FGFR3 alterations in patients who develop locally advanced or metastatic urothelial cancer, and their association with tumor subtype and clinical outcomes in patients treated with erdafitinib versus pembrolizumab.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on bladder cancer, and a presentation by Dr. Syed Arsalan Ahmed Naqvi discussing cost-effectiveness analysis of contemporary first-line agents in locally advanced/metastatic urothelial carcinoma. EV-302¹ and CheckMate 901² demonstrated significant survival benefit with enfortumab vedotin + pembrolizumab and gemcitabine + cisplatin + nivolumab as first-line therapy, respectively, in patients with locally advanced/metastatic urothelial carcinoma. However, whether these treatments are cost-effective or not remains unclear.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between May 31 and June 4 was host to the Session: Managing Variant Histologies in Urothelial and Renal Cell Cancers. Dr. Eva Katharina Masel talked about the considerations in treating and palliating variant Genitourinary Cancers where no standard of care exists.

Dr. Masel began her presentation by saying palliative care is not just about end-of-life care; it's about living in the best possible way with the disease. Palliative care professionals aim to be seen as a lighthouse, guiding patients through the storms that may come.

She continues by drawing a parallel between trauma care and palliative medicine. Just as trauma care follows the ABCDE approach (Airway, Breathing, Circulation, Disability, Expose), palliative medicine utilizes the ABCD approach, which stands for Attitude, Behavior, Compassion, and Dialogue. This framework applies across all areas of medicine. Regardless of a patient's age or health condition, the core values of kindness, respect, and dignity remain indispensable. This approach serves as a reminder to practitioners about the importance of both caring for and caring about their patients. (1)

Palliative care can be defined as specialized healthcare focused on improving quality of life for patients with serious illnesses and can aid other clinicians in addressing patients' unmet symptoms, coping mechanisms, and communication needs. The American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). guidelines recommend integrating palliative care into standard oncological treatment based on multiple randomized trials demonstrating significant improvements in physical well-being, patient satisfaction, and goal-concordant care. (2) It is crucial to understand the need for a palliative care consultation when caring for cancer patients, Dr Masel mentioned 7 indications that we should keep in our minds for a timely referral to palliative medicine:

1. High health care resource utilization
2. Persistent pain or high risk of poor pain management
3. High non-pain symptom burden or symptoms refractory to initial management
4. Limited anticancer treatment options
5. Need for advanced communication skills
6. Complex patient and/or caregiver circumstances
7. Oncology care team challenges

Referrals to palliative care often occur in the late and advanced stages of the disease, leading to untreated symptoms, patient distress, and unnecessary aggressive treatments at the end of life. One major barrier to early referrals is the common association of palliative care with hopelessness, cessation of cancer treatment, and death. Although physicians may explain the benefits of early palliative care, overcoming patients’ negative preconceptions can be challenging. To help facilitate these conversations, the metaphor "Palliative Care Is the Umbrella, Not the Rain" can be used in clinical practice. This metaphor helps guide discussions in advanced cancer, making patients more open to seeing a palliative care specialist. (3)

Dr. Masel discussed the importance of communication with cancer patients and introduced another framework: CARE, which stands for Communicate, Advocate, Respect, and Empathize. Briefly, this means we should communicate warmly and welcomingly with patients, advocate on behalf of patients, families, colleagues, and ourselves, respect and embrace differing values, opinions, and viewpoints, and empathize with and acknowledge the feelings of others.

There is abundant evidence that patients nearing the end of life often feel they no longer matter. This sense of burden can affect both the patients, who may feel like a burden to others, and their family members, who may feel helpless and exhausted, reinforcing the patients' feelings of burden. Intensive caring involves finding ways to remind patients that they still matter. A foundational element of this approach is non-abandonment, which requires committed, ongoing care and compassion, even when patients no longer care about themselves. The assurance of continued support and care is crucial in helping patients feel valued. The elements of intensive caring are illustrated in the table below:

As physicians caring for cancer patients, we often tend to distance ourselves from palliative care. This behavior is akin to the phenomenon in nature known as "crown shyness," where a tree's leaves withdraw from the leaves of other trees. Instead, we should avoid this distancing and work together as a team to improve the care of our cancer patients.

Dr Masel went on to discuss the continuum of palliative care, this implies that to improve equity and inclusivity in palliative care we have to follow an individual-centered strategy endorsed by the community and promoting change across various fronts:

• Individual (patient and caregiver)
• Interpersonal (health care team)
• Organizational
• At the policy level

Ensuring fair access is essential throughout the entire spectrum of palliative care services, starting from early interventions and extending to symptom-focused treatment, hospice care, end-of-life support, and bereavement assistance. The continuum of care is illustrated in the figure below.(5)

Dr. Masel discussed a randomized clinical trial published in 2010 involving patients newly diagnosed with metastatic non-small-cell lung cancer. Participants were allocated to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Results showed that those assigned to early palliative care demonstrated a better quality of life compared to those receiving standard care. Additionally, fewer patients in the early palliative care group exhibited depressive symptoms, as assessed by the Hospital Anxiety and Depression Scale (HADS-D, HADS-A) and the Patient Health Questionnaire-9 (PHQ-9) (6).

Finally, the palliative care intervention should be directed to:

• Illness understanding/education
  • Inquire about illness and prognostic understanding
  • Offer clarification of treatment goals
• Symptom management
  • Inquire about uncontrolled symptoms, referral or prescriptions, if necessary
• Mode of decision making
  • Assist with treatment decision-making, if necessary
• Coping with life threatening illness
  • Patients and caregivers

Dr Masel wrapped up her presentation with following key messages:

• Palliative Care Is the Umbrella, Not the Rain
• We have to improve our communication, this is a clinical skill and words matter
• It is not either or, but both - Oncology and Palliative Care
• How people die remains in the memory of those who live on

Presented By: Eva Katharina Masel, MD, PhD, Full Professor and Head of the Clinical Division of Palliative Care at the Medical University of Vienna

Written By: Julian Chavarriaga, MD – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024

References:

1. Chochinov HM. Dignity and the essence of medicine: the A, B, C, and D of dignity conserving care. BMJ. 2007 Jul 28;335(7612):184-7. doi: 10.1136/bmj.39244.650926.47. PMID: 17656543; PMCID: PMC1934489.
2. Hugar LA, Wulff-Burchfield EM, Winzelberg GS, Jacobs BL, Davies BJ. Incorporating palliative care principles to improve patient care and quality of life in urologic oncology. Nat Rev Urol. 2021 Oct;18(10):623-635. doi: 10.1038/s41585-021-00491-z. Epub 2021 Jul 26. PMID: 34312530; PMCID: PMC8312356.
3. Zimmermann C, Mathews J. Palliative Care Is the Umbrella, Not the Rain-A Metaphor to Guide Conversations in Advanced Cancer. JAMA Oncol. 2022 May 1;8(5):681-682. doi: 10.1001/jamaoncol.2021.8210. PMID: 35297961.
4. Chochinov HM. Intensive Caring: Reminding Patients They Matter. J Clin Oncol. 2023 Jun 1;41(16):2884-2887. doi: 10.1200/JCO.23.00042. Epub 2023 Apr 19. PMID: 37075272; PMCID: PMC10414729.
5. Koffman J, Shapiro GK, Schulz-Quach C. Enhancing equity and diversity in palliative care clinical practice, research and education. BMC Palliat Care. 2023 Jun 5;22(1):64. doi: 10.1186/s12904-023-01185-6. PMID: 37271813; PMCID: PMC10239712.
6. Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, Billings JA, Lynch TJ. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010 Aug 19;363(8):733-42. doi: 10.1056/NEJMoa1000678. PMID: 20818875.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on bladder cancer, and a presentation by Dr. Shilpa Gupta discussing age and other criteria influencing non-treatment of patients with locally advanced or metastatic urothelial carcinoma. Bladder cancer is the 10^th most common cancer globally, with locally advanced or metastatic urothelial carcinoma being the most advanced stages. Although the standard of care for first-line treatment of locally advanced or metastatic urothelial carcinoma is changing rapidly with the emergence of new therapies, guidelines recommend that eligible patients should receive some form of systemic therapy.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on kidney cancer trials in progress, and a presentation by Dr. Eric Jonasch discussing the trial design of a phase 1b/2 study of combination ¹⁷⁷Lu girentuximab + cabozantinib and nivolumab in treatment-naive patients with advanced clear cell RCC.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on bladder cancer, and a presentation by Dr. Yohann Loriot discussing long-term outcomes of avelumab from the JAVELIN Bladder 100 trial in patients with histological subtypes. Results from the phase 3 JAVELIN Bladder 100 trial led international treatment guidelines to recommend avelumab first-line maintenance as a standard-of-care treatment for patients with advanced urothelial carcinoma without progression after first-line platinum-based chemotherapy.¹

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer, and a presentation by Dr. Praful Ravi discussing the prognostic impact of residual cancer burden on long-term outcomes after neoadjuvant androgen receptor pathway inhibitor and radical prostatectomy for high-risk localized prostate cancer.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31^st and June 4^th, 2024 was host to a session addressing techniques to minimize the effects of androgen deprivation therapy (ADT) while explore alternatives in prostate cancer management. Dr. Brian Gonzalez discussed patient-centered approaches to improve quality of life and mitigate the adverse effects of ADT.

Behavioral interventions, such as cognitive behavioral therapy (CBT) and physical activity, can help mitigate adverse effects of ADT, including fatigue, depressive symptoms, and sleep disruption. Behavioral strategies play a critical role in patient-centred clinical practice and can help improve health related quality of life.

ADT has numerous adverse effects that may impact quality of life, including:

• Vascular disorders
• Reproductive system disorders (e.g., impotence and loss of libido)
• General disorders (e.g., sleep disturbances)
• Psychiatric disorders (e.g., depression)
• Metabolic changes (e.g., weight gain)
• Musculoskeletal changes (e.g., muscle atrophy)

The NCCN Survivorship Guidelines recommend behavioral interventions for the management of ADT-related symptoms that:

• Address multiple symptoms simultaneously
• Minimize side effects
• Are associated with a low economic burden
• Actively engage patients
• Improve health-related quality of life
• Enhance patient-centered clinical practice

One such intervention is cognitive behavioral therapy. This is a biopsychosocial approach focused on teaching solution-focused strategies, by:

• Refocusing away from negative thoughts about symptoms towards more realistic, helpful thoughts
• Behavioral activation and exposure to feared experiences.
• Improving health behaviors
• Managing stress
• Optimizing social support
• Increasing self-efficacy

Another important behavioral intervention is physical activity, with the benefits among cancer survivors summarized below.

Currently, the 2014 American Cancer Society guidelines for prostate cancer recommend 150 minutes of physical activity per week, without specifying the type. Randomized controlled trials now support combined resistance and aerobic exercise programs in the context of ADT without bone metastases to improve muscle mass, strength, physical function, and balance.¹

These behavioral interventions may have synergistic effects by simultaneously targeting/counteracting the adverse effects of ADT, as illustrated below:

Behavioral treatments can improve health-related quality of life in numerous ways:

• Health promotion: Improve body weight and composition, physical activity levels, and PSA levels
• Physical side effect management: Fatigue, muscle strength, peak oxygen intake, bone health, sexual function, and incontinence.
• Psychosocial functioning: Depression, anxiety, and overall quality of life

Although the benefits of these behavioral interventions are universally accepted, their adoption in routine clinical practice remains underwhelming. In 2023, Ehlers et al conducted a stakeholder-engaged, mixed-methods, hybrid implementation study to identify barriers to real-world implementation of these behavioral interventions.² Lack of awareness, both at the physician and patient levels, was an important barrier, as well as clinical practice barriers (e.g., workflow, lack of personnel/skills to provide behavioral training, no specialists available in the community to refer patients to). They proposed the following model for implementing group cognitive behavioral therapy in an interdisciplinary cancer center:

1. Stakeholder (physicians/nurses and patients/caregivers) engagement and adaptation of cognitive behavioral therapy delivery
2. User testing and adaptation of cognitive behavioral therapy content
3. Implementation of adapted cognitive behavioral therapy

Presented By: Brian D. Gonzalez, PhD, Associate Center Director for Research Diversity & Workforce Development, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Written By: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, May 31 – Tues, June 4, 2024

References:

1. Sanft T, Day A, Ansbaugh S, et al. NCCN Guidelines® Insights: Survivorship, Version 1.2023. J Natl Compr Canc Netw. 2023;21(8): 792-803.
2. Ehlers SL, Gudenkauf LM, Kacel EL, et al. Real-World Implementation of Best-Evidence Cancer Distress Management: Truly Comprehensive Cancer Care. J Natl Compr Canc Netw. 2023;21(6): 627-35.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer trials in progress, and a presentation by Dr. Christina Dieli-Conwright discussing the trial design of the FIERCE trial, debunking the frailty-sarcopenia-ADT axis in metastatic prostate cancer with multicomponent exercise. Metastatic prostate cancer incidence is growing despite a decrease in the prevalence of prostate cancer. ADT, the mainstay treatment for metastatic prostate cancer, is accompanied by a number of side effects, such as decline in muscle mass and physical function, leading to the exacerbation of age-related conditions including frailty and sarcopenia.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer, and a presentation by Dr. Deepak Kilari discussing results of a phase II trial of enzalutamide with 5-alpha reductase inhibitors as an ADT–sparing approach for older men with castration-sensitive prostate cancer (CSPC).

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL between May 31^st and June 4^th, 2024 was host to a session addressing techniques to minimize the effects of androgen deprivation therapy (ADT) while explore alternatives in prostate cancer management. Dr. Ashwin Sachdeva discussed the appropriate use and timing of bone resorptive agents in patients with advanced prostate cancer.

(UroToday.com) The 2024 American Society of Clinical Oncology (ASCO) annual meeting featured a session on prostate cancer, and a presentation by Dr. Arshit Narang discussing the impact of alterations in tumor suppressor genes on survival outcomes in patients with de novo metastatic castration-sensitive prostate cancer (CSPC) receiving ADT with androgen receptor pathway inhibition or docetaxel.