Russ Conroy

Neoadjuvant chemotherapy plus chemoradiation was safe and effective for long-term bladder preservation in select patients with muscle-invasive bladder cancer.

Among patients with nonmetastatic, muscle-invasive bladder cancer (MIBC), treatment with neoadjuvant cisplatin-based combination chemotherapy (NAC) plus bladder-saving concurrent chemoradiation therapy was effective and safe in the long term, according to findings presented at the 2025 ASCO Genitourinary Cancers Symposium.

Efficacy data revealed that after a median follow-up of 96 months, the median disease-free survival (DFS) in patients treated with NAC followed by CRT for nonmetastatic MIBC was 56.6 months, with a five-year DFS rate of 49.2%. Furthermore, the median bladder intact DFS (BI-DFS) in this patient group was 45.6 months, and the five-year BI-DFS was 47.6%. Additionally, the median overall survival (OS) was 105 months with a five-year OS rate of 62.2%.

“[Neoadjuvant, cisplatin-based chemotherapy plus] concurrent chemoradiotherapy is a safe and effective bladder-sparing approach with encouraging long-term outcomes in carefully selected patients with MIBC,” Dr. Meghan E. Mahoney of the Division of Medical Oncology at the Tom Baker Cancer Centre in Calgary, Alberta, Canada, wrote in the presentation with study coinvestigators.

The study investigators contextualized the study background by highlighting a paucity of long-term data on the efficacy and tolerability of trimodality therapy in patients with MIBC opting for bladder-sparing approaches.

Neoadjuvant: administered prior to the primary treatment, such as surgery.

Disease-free survival: the time after treatment that a patient lives without signs or symptoms of cancer.

Overall survival: the time that a patient lives, regardless of disease stats.

Maximal transurethral resection of a bladder tumor: the removal of a tumor through the urethra.

Cystoscopy: a procedure to examine the bladder and urethra.

Radical cystectomy: surgical removal of the bladder.

ECOG performance status: a way to measure patients’ ability to complete daily tasks, with a lower number indicating greater independence.

Hydronephrosis: when the kidney becomes swollen due to a buildup of urine.

A total of 56 patients with nonmetastatic MIBC who were given NAC followed by bladder-sparing CRT between 2008 and 2017 at the Princess Margaret and Durham Regional Cancer Centers were included in the retrospective chart review. The primary outcomes were five-year DFS, BI-DFS and OS.

Patients initially underwent maximal transurethral resection of a bladder tumor (TURBT) prior to neoadjuvant treatment with gemcitabine plus cisplatin for two to four cycles. Following the second cycle of neoadjuvant treatment, imaging occurred in all patients, and those experiencing disease progression underwent cystoscopy before undergoing immediate radical cystectomy plus lymph node dissection. Furthermore, following the fourth cycle, all patients underwent imaging and cystoscopy, and those who experienced disease progression underwent maximal re-TURBT before undergoing immediate radical cystectomy plus lymph node dissection.

Responders to neoadjuvant treatment and those with stable disease were treated with external beam radiation therapy (EBRT) at a dose of 60 to 66 Gy to the bladder and pelvic lymph nodes, as well as concurrent weekly cisplatin at 40 mg/m

 for six weeks. Surveillance cystoscopy, imaging and urine cytology occurred after CRT every three to four months.

During the surveillance period, those with no recurrence continued surveillance. Additionally, those with non-MIBC recurrence repeated TURBT with or without Bacillus Calmette-Guerin treatment. Those with MIBC recurrence underwent salvage cystectomy. Furthermore, patients who experienced distant recurrence during the surveillance period were treated with systemic therapy.

Patients included in the analysis had a median age of 72 years and 79% were male. Additionally, 55% of patients had formerly smoked, with 20% of patients identifying as current smoking. Patients primarily had an ECOG performance status of 0 (66%) or 1 (32%). The median creatinine clearance was 59 mL/min, the median tumor size was 4.1 cm and 25% of patients had hydronephrosis.

Patients had clinical stage 2 (59%), 3 (34%), or 4 (7%) disease, and the most common histologies were pure urothelial carcinoma (UC; 63%), squamous UC (23%) and plasmacytoid variant UC (13%). A total of 30% and 18% of patients had carcinoma-in-situ and lymphovascular invasion, respectively. Overall, 41% of patients experienced disease recurrence, with 20% of patients experiencing local recurrence, 14% experiencing recurrence requiring cystectomy and 21% experiencing distant recurrence.

The primary NAC regimens were gemcitabine/cisplatin every 21 days (34%) or split gemcitabine/cisplatin every 21 days (57%). Overall, 5%, 32% and 63% of patients underwent two, three and four NAC cycles, with 95% of patients completing planned NAC treatment. The most common grade 3 (severe) or 4 (life-threatening) NAC-related toxicities included neutropenia (11%), thrombocytopenia (4%), infection (4%) and anemia (2%). NAC dose reductions occurred in 55% of patients with a median dose reduction percentage of 25%, and 39% of patients experienced NAC dose delays.

Additionally, the reasons for administering trimodality therapy included patient preference (59%), comorbidities related to radical cystectomy (36%) or some combination of both factors (4%). Most patients had a planned radiation therapy dose of 60 Gy or greater (91%), and all patients completed planned radiation. Furthermore, 86% of patients completed 60% or more of planned concurrent cisplatin dosing.

“Long-term outcomes of neoadjuvant chemotherapy (NAC) before bladder-sparing chemoradiotherapy (CRT) for patients with nonmetastatic, muscle-invasive bladder cancer (MIBC),” by Dr. Meghan E. Mahoney, et al., 

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Articles

Neoadjuvant cisplatin-based chemotherapy combined with bladder-sparing concurrent chemoradiation therapy demonstrates long-term efficacy and safety in nonmetastatic muscle-invasive bladder cancer (MIBC). After a median follow-up of 96 months, the median disease-free survival (DFS) was 56.6 months, with a five-year DFS rate of 49.2%. The median bladder intact DFS was 45.6 months, and the five-year rate was 47.6%. Overall survival (OS) reached a median of 105 months, with a five-year OS rate of 62.2%. Trimodality therapy was chosen due to patient preference and comorbidities.

For some patients with bladder cancer, neoadjuvant chemotherapy plus bladder-saving concurrent chemoradiation therapy was effective in the long term.

Neoadjuvant Chemotherapy Plus Chemoradiation Safe, Effective in Bladder Cancer

Palliative care in young adults with early-onset colorectal cancer reduced invasive procedures, costs and increased DNR orders, improving end-of-life comfort.

Among patients with early-onset colorectal cancer (CRC), palliative care involvement may reduce invasive and uncomfortable intervention use, resulting in a subjective improvement in patient end-of-life (EOL) comfort, according to findings from a real-world study presented at the 

2025 ASCO Gastrointestinal Cancer Symposium

Data revealed that among patients with early-onset CRC who died during hospitalization, palliative care was associated with significant reductions in multiple invasive interventions. Between two cohorts, one treated with palliative care (2,425 patients), and another not treated with palliative care (1,635 patients), blood transfusion was reported in 14.8% and 22.6% of patients, mechanical ventilation was reported in 20.4% and 43.4% of patients and vasopressor use was reported in 6.2% and 8.6%, respectively.

Additional data revealed a significant reduction in total charges with palliative care, with a median of $99,367 (SD, 151,864) versus $131,993 (SD, 206,404) without palliative care. Furthermore, do not resuscitate (DNR) orders were significantly increased with palliative care, which was reported in 83.3% of this cohort versus 44.6% in patients without palliative care.

Vasopressor: medicine that raises blood pressure.

Overall survival: the time a patient lives, regardless of disease status.

“Inclusion of palliative care in terminal hospital stays for patients with early-onset CRC was associated with less use of invasive and uncomfortable interventions, resulting in significantly reduced expenditure on futile measures, and likely a subjective improvement in patient [EOL] comfort,” Dr. Suriya Baskar, resident physician in the Internal Medicine Department at the Brooklyn Hospital Center, wrote in the study with coinvestigators. “The results of this study support the integration of palliative care in [patients with] early-onset [CRC] presenting with advanced disease.”

According to the National Cancer Institute’s website, palliative care aims to improve quality of life and reduce pain for individuals with serious or life-threatening illnesses, such as cancer. The goal is to prevent or treat disease symptoms and treatment side effects as early as possible. This care also addresses the psychological, social and spiritual issues arising from the illness or its treatment. For patients with cancer, palliative care can include therapies like surgery, radiation or chemotherapy to remove, shrink or slow tumor growth causing pain. It may also involve support for family and caregivers. Palliative care can be provided alongside other treatments from diagnosis to end of life.

The median age of patients receiving palliative care was 42.1 years compared to 41.9 years for those not receiving such care. Women made up 44.3% of the palliative care group and 39.8% of the group that did not receive palliative care.

The mean length of hospital stay was 8.8 days for patients receiving palliative care and 9.1 days for those who did not. Chemotherapy was administered to 2.9% of the palliative care group and 2.8% of the other group.

The study was conducted in the context of prior proven benefits associated with palliative care in elderly patients with advanced cancers, with an identified paucity of data regarding the benefits of palliative care among younger patients with aggressive disease. A study published in 

 found that among patients with advanced cancers, those who received early palliative care (73 patients) experienced better quality of life (QOL) at 18 months than those who did not (71 patients).

Furthermore, a greater difference in existential well-being index was observed among patients who received palliative care versus those who did not at 24-week follow-up (0.82 points). Additionally, two-year overall survival was significantly improved among patients who received early palliative care 10 or more times.

"Impact of inpatient palliative care on end-of-life care among patients with early-onset colorectal cancer" by Dr. Suriya Baskar, et al., 

Palliative care involvement in early-onset colorectal cancer (CRC) patients significantly reduces invasive interventions and hospital charges, enhancing end-of-life comfort. A study presented at the 2025 ASCO Gastrointestinal Cancer Symposium showed that palliative care led to fewer blood transfusions, mechanical ventilation, and vasopressor use. It also increased do-not-resuscitate orders and reduced hospital costs. The study supports integrating palliative care for advanced early-onset CRC patients, aligning with previous findings of improved quality of life and survival in advanced cancer patients receiving early palliative care.

Palliative care for young adults with colorectal cancer reduced invasive procedures, costs and increased DNR orders.

Palliative Care May Reduce Invasive Intervention Use in Early-Onset CRC

Adding Herceptin and Perjeta to chemotherapy increased toxicity in patients with HER2+ gastric cancers.

Herceptin plus chemotherapy showed numerical improvements in overall survival (OS) and progression-free survival (PFS) for HER2-positive gastric and gastroesophageal junction (GEJ) cancers, although these benefits were not sustained following a change in the chemotherapy regimen, according to data from the phase 2 INNOVATION trial, which were presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium.

The major pathological response rate (mpRR) was 23.3% in patients who received chemotherapy alone (33 patients), 37% in those who received chemotherapy plus Herceptin (64 patients) and 26.4% among those who received chemotherapy in combination with Herceptin and Perjeta (pertuzumab; 64 patients). Investigators administered surgery to 84.8%, 98.4% and 92.2% of patients in each respective arm.

When stratifying results by the chemotherapy backbone, the mpRR in the chemotherapy plus Herceptin/Perjeta, chemotherapy/Herceptin and chemotherapy alone arms, respectively, were 12.5%, 16.7% and 8.3% when a cisplatin/Xeloda (capecitabine) or 5-flurorouracil backbone was administered. With a backbone of fluorouracil plus leucovorin, oxaliplatin and docetaxel (FLOT); folinic acid, fluorouracil and oxaliplatin (FOLFOX); or Xeloda/oxaliplatin (CAPOX), the respective mpRRs were 37.9%, 53.3% and 33.3%.

Across the overall population, the median PFS was not reached (NR) in the chemotherapy monotherapy and chemotherapy/Herceptin arms, meaning that more than half of patients were alive without disease progression when this was assessed. In addition, data showed a median of 3.32 years in the Herceptin/Perjeta plus chemotherapy arm. Compared with chemotherapy alone, the risk of progression or death decreased with Herceptin/chemotherapy but increased with the addition of Perjeta.

Stratified PFS results showed 3-year rates of 57.1% in the chemotherapy alone arm, 64.2% in the chemotherapy/Herceptin arm and 50.4% in the Perjeta triplet arm before investigators instituted a protocol amendment that changed the chemotherapy backbone to FLOT across the study’s European sites. Following this protocol amendment, the three-year PFS rates were 68.4%, 65% and 53.3% in each respective arm.

The median OS was not reached across all 3 treatment arms in the overall population, with 3-year rates of 75.6% when using chemotherapy alone, 76.9% with the addition of Herceptin and 65.2% when adding Herceptin and Perjeta. The risk of death was numerically lower with Herceptin/chemotherapy versus chemotherapy alone but higher with Herceptin/Perjeta plus chemotherapy.

Before the trial amendment regarding the chemotherapy backbone, the three-year OS rates were 78.6% using chemotherapy alone, 83.6% when adding Herceptin and 68.3% with the addition of Herceptin and Perjeta. The three-year OS rates following the amendment were 73.3%, 72.2% and 62.2%, respectively.

“The INNOVATION study did not meet its primary end point. The combination of chemotherapy plus [Herceptin] and [Perjeta] was associated with higher toxicity and no advantage. [PFS] and [OS] were numerically improved when adding [Herceptin] to chemotherapy doublet, but not after the amendment when patients received FLOT,” Dr. Anna Dorothea Wagner, a consultant, senior lecturer and head of the Gastrointestinal Cancer Clinic in the Department of Oncology at the University Hospital of Lausanne, Switzerland, stated in the presentation.

“On the basis of its very high [mpRR], the addition of [Herceptin] to chemotherapy may be considered, especially when tumor downsizing is needed to achieve a curative resection,” she added.

Investigators of this phase 2 trial randomly assigned patients to receive chemotherapy alone in arm A, chemotherapy plus Herceptin in arm B, or chemotherapy in combination with Herceptin and Perjeta in arm C. All patients received neoadjuvant and adjuvant chemotherapy consisting of CAPOX, modified FOLFOX6, FLOT, cisplatin/Xeloda, or 5-fluorouracil. Additionally, patients received perioperative Herceptin in arm B and perioperative Herceptin/Perjeta in arm C.

The trial’s primary end point was the mpRR, defined as the proportion of patients with less than 10% viable tumor cells following neoadjuvant therapy per central review. Secondary end points included recurrence-free survival (RFS), PFS and OS.

Patients with HER2-positive gastric and GEJ adenocarcinoma amenable to gastrectomy or esophagectomy were eligible for enrollment on the trial. Other requirements for study entry included having 1B to 3 tumors and HER2 overexpression.

Of note, four cycles of FLOT were administered to 93.8%, 93.3% and 80.6% of the chemotherapy alone, chemotherapy/Herceptin and chemotherapy plus Herceptin/Perjeta arms, respectively. Wagner highlighted lower rates of FLOT dose intensity in the arm that received Perjeta, which included a median dose intensity of 87.9% for oxaliplatin, 85.5% for docetaxel, 93.2% for folinic acid and 82% for 5-fluorouracil.

Additional efficacy findings showed that RFS and OS improved in patients who achieved a mpR compared with those who did not.

Notable grade 3 (severe) side effects in the chemotherapy alone, chemotherapy/Herceptin and chemotherapy plus Herceptin/Perjeta arms, respectively, included diarrhea (5.9% versus 3% versus 26.1%) and neutrophil count decreases (32.4% versus 21.2% versus 21.7%). There were two patient deaths in the chemotherapy/Herceptin arm due to neutropenia plus pneumonia and sepsis in one patient and postoperative biliary peritonitis in another. Investigators noted two patient deaths in the Perjeta arm, which included one due to neutropenic sepsis with mucositis and one due to vast cerebral ischemia after surgery.

"INNOVATION": integration of trastuzumab (T), with or without pertuzumab (P), into perioperative chemotherapy of HER-2 positive stomach cancer: overall survival results. Dr. Anna Dorothea Wagner, et al. 

Herceptin combined with chemotherapy demonstrated numerical improvements in overall survival (OS) and progression-free survival (PFS) for HER2-positive gastric and gastroesophageal junction cancers, but these benefits diminished after a chemotherapy regimen change. The phase 2 INNOVATION trial revealed that adding Herceptin to chemotherapy increased major pathological response rates, while the addition of Perjeta led to higher toxicity without added benefit. The trial's primary endpoint, major pathological response rate, was not met. The study highlighted the potential of Herceptin in tumor downsizing for curative resection.

In the INNOVATION trial, adding Herceptin and Perjeta to chemotherapy increased toxicity in patients with HER2-positive gastric cancers.

Herceptin Combo Shows Limited Benefit in Gastric/GEJ Cancer

Opdivo plus Yervoy improved survival compared to Opdivo alone in patients with mismatch repair deficient or microsatellite instability-high metastatic colorectal cancer.

Opdivo (nivolumab) plus Yervoy (ipilimumab) improved progression-free survival (PFS) compared to Opdivo alone in patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC), according to the CheckMate 8HW trial presented at the 

Among patients with centrally confirmed MSI-H or dMMR status, data showed a median PFS that was not reached with Opdivo plus Yervoy versus 39.3 months with Opdivo monotherapy, meaning that more than half of patients in the study group had not experienced disease progression. The PFS rates in each respective arm across this population were 76% versus 63% at 12 months, 71% versus 56% at 24 months and 68% versus 51% at 36 months. Among all randomly assigned patients, the median PFS was 54.1 months versus 18.4 months, respectively.

PFS outcomes generally favored the Opdivo/Yervoy arm across all lines of therapy and prespecified patient subgroups based on factors including age, sex, ECOG performance status and liver metastases.

In the MSI-H/dMMR tumor population, the objective response rate (ORR) was 71% using Opdivo plus Yervoy versus 58% using Opdivo alone. Of note, complete responses (CRs) and partial responses (PRs) occurred in 30% and 40% of the Opdivo/Yervoy arm and 28% and 30% of the Yervoy monotherapy arm, respectively. Additionally, the median time to response (TTR) in each arm was 2.8 months versus 2.8 months, and the median duration of response (DOR) was not reached versus not reached.

Progression-free survival: the length of time during and after treatment when a patient with cancer lives without the disease worsening.

Mismatch repair deficient: a defect in the body’s ability to fix errors that occur when DNA is copied in cells.

Microsatellite instability-high: when there are many repetitive sequences of DNA in the tumor cells.

ECOG performance status: a toll to assess a patient’s overall health and ability to perform daily activities. For example, 0 indicates that a patient is fully active without restrictions, whereas 1 indicates a patient who is restricted in physical strenuous activity but is ambulatory and able to carry out work of a light nature.

Objective response rate: the percentage of patients with a complete or partial response to treatment.

Complete response: all signs of cancer have disappeared after treatment.

Partial response: the cancer shrunk or showed improvement in response to treatment, but has not completely disappeared.

Adrenal insufficiency: when the adrenal glands do not produce enough of a certain hormone, primarily cortisol.

Colitis: inflammation of the inner lining of the colon.

“[Opdivo] plus [Yervoy] demonstrated statistically significant and clinically meaningful improvement in PFS versus [Opdivo] in patients with centrally confirmed [MSI-H or dMMR metastatic CRC] across all lines [of therapy]. [There were] early and sustained separation of PFS curves after the first scan,” Dr. Thierry André, a professor of medical oncology at the Sorbonne Université in Paris and head of the Medical Oncology Department at the Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris, France, stated in the presentation. “These results, combined with the previously reported superior PFS with [Opdivo/Yervoy] versus chemotherapy in the first-line setting, establish [Opdivo] plus [Yervoy] as a new standard of care for patients with MSI-H/dMMR metastatic [CRC].”

In the phase 3 trial, patients were randomly assigned to receive Opdivo monotherapy (353 patients), Opdivo plus Yervoy (354 patients) or investigator’s choice of modified folinic acid plus fluorouracil and oxaliplatin (mFOLFOX6) or folinic acid plus fluorouracil and irinotecan (FOLFIRI) with or without Avastin (bevacizumab) or Erbitux (cetuximab; 132 patients).

The trial’s primary end points were PFS for Opdivo/Yervoy versus chemotherapy in the first-line setting and PFS for Opdivo versus Opdivo/Yervoy across all lines of treatment. Secondary end points included ORR, health-related quality of life (HRQOL) and safety.

Patients with histologically confirmed unresectable or metastatic CRC, MSI-H or dMMR status, no prior treatment with immunotherapy and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial.

Of note, 352 patients in the Opdivo/Yervoy arm and 351 in the Opdivo monotherapy arm received study treatment, with ongoing treatment at the time of analysis reported for 6% and 4% of patients, respectively. Additionally, 49% and 57% of patients discontinued treatment, mostly due to disease progression (23% versus 39%). The median duration of treatment in each arm was 20.5 months and 16.4 months, with deaths reported in 29% and 42% of patients.

Data showed HRQOL improvements in the Opdivo/Yervoy arm. The mean changes in HRQOL scores were typically positive in both arms, with outcomes in the Opdivo/Yervoy arm reaching the trial’s prespecified threshold for meaningful change from baseline starting at week 21.

Any-grade treatment-related side effects occurred in 81% and 71% of patients who received Opdivo/Yervoy and Opdivo monotherapy, respectively. Common any-grade treatment-related side effects in each arm included itching (26% versus 18%), diarrhea (20% versus 17%) and underactive thyroid (17% versus 9%). Additionally, the most common grade 3 (severe) or higher treatment-related side effect in each arm was adrenal insufficiency (2% versus less than 1%).

Regarding immune-mediated side effects, the most common any-grade non-endocrine events in the combination and monotherapy arms, respectively, included rash (7% versus 6%), diarrhea or colitis (6% versus 4%), and hepatitis (4% versus 1%). Additionally, the most common endocrine events in each arm included underactive thyroid or inflammation of the thyroid gland (18% versus 9%), overactive thyroid (12% versus 5%) and adrenal insufficiency (10% versus 3%).

First results of nivolumab (NIVO) plus ipilimumab (IPI) versus NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) from CheckMate 8HW. Dr. Thierry André, et al. 

The combination of Opdivo (nivolumab) and Yervoy (ipilimumab) significantly improved progression-free survival (PFS) in patients with mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC) compared to Opdivo alone, as demonstrated in the CheckMate 8HW trial. The study showed superior PFS rates and objective response rates (ORR) for the combination therapy across various patient subgroups. The trial also highlighted improvements in health-related quality of life (HRQOL) and manageable safety profiles, establishing the combination as a new standard of care for this patient population.

The combination of Opdivo and Yervoy is supported by updated results as a standard of care for MSI-H or dMMR metastatic colorectal cancer.

Russ Conroy

Neoadjuvant Chemotherapy Plus Chemoradiation Safe, Effective in Bladder Cancer

Palliative Care May Reduce Invasive Intervention Use in Early-Onset CRC

Herceptin Combo Shows Limited Benefit in Gastric/GEJ Cancer

Opdivo Plus Yervoy Improves Outcomes in Metastatic Colorectal Cancer Subset

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