What's new in oncology

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

BREAST CANCER

RSClinN+ tool for node-positive, hormone receptor-positive, HER2-negative breast cancer (May 2025)

For those with node-positive, hormone receptor-positive, HER2-negative breast cancer, a tool called RSClinN+ has been developed, which integrates clinicopathologic information (grade, tumor size, age) with recurrence scores (RS) based on gene expression profiling. In the validation study, the RSClinN+ model provided better prognostic information than the RS alone or a clinicopathologic model alone, both for pre- and postmenopausal women [1]. While it provided estimates of chemotherapy benefit for postmenopausal patients, its ability to predict benefit for chemotherapy in premenopausal patients was more limited. We consider results of this tool in adjuvant chemotherapy decisions for postmenopausal patients, alongside other factors including patient preferences and comorbidities. However, it should not influence chemotherapy decisions in premenopausal patients with node-positive disease. (See "Deciding when to use adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer", section on 'Using clinical information to refine estimates of chemotherapy benefit'.)

Eribulin in HER2-positive breast cancer (April 2025)

For patients with metastatic HER2-positive breast cancer, standard initial therapy includes a taxane and HER2-targeted therapy, but there are limited data regarding alternative chemotherapy agents. In a randomized trial, eribulin demonstrated similar median progression-free survival as a taxane (14 versus 13 months) when used as the initial chemotherapy backbone in patients receiving trastuzumab and pertuzumab. Although eribulin caused more grade ≥3 neutropenia and peripheral sensory neuropathy, there were lower rates of infusion reactions, skin-related toxicity, diarrhea, and edema [2]. These data support eribulin as an alternative chemotherapy backbone with a different toxicity profile to taxanes for patients with metastatic HER2-positive breast cancer. (See "Systemic treatment for HER2-positive metastatic breast cancer", section on 'Options irrespective of hormone receptor status'.)

CDK 4/6i after prior aromatase and CDK 4/6 inhibition in hormone receptor-positive, HER2-negative breast cancer (March 2025)

Cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i) plus endocrine therapy (ET) are standard initial treatment for hormone receptor-positive (HR+), HER2-negative advanced breast cancer, but the role of continued CDK 4/6i upon progression is unclear. In a randomized trial in 368 patients with disease progression on prior CDK 4/6i plus an aromatase inhibitor (AI), fulvestrant plus the CDK 4/6i abemaciclib improved six-month progression-free survival over fulvestrant alone (50 versus 37 percent) [3]. Although we often use other targeted therapies after a CDK 4/6i plus AI in those with genetic alterations in the PIK3CA pathway or in ESR1, we consider abemaciclib plus fulvestrant to be an appropriate option, particularly in those whose tumors lack such alterations. (See "Treatment for hormone receptor-positive, HER2-negative advanced breast cancer", section on 'ESR1 wild-type'.)

Overall survival with T-DM1 in residual HER2-positive breast cancer (February 2025)

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine, a microtubule inhibitor. Previously, in a randomized trial in 1486 females with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and trastuzumab, adjuvant treatment with 14 cycles of T-DM1 improved invasive disease-free survival compared with trastuzumab. In subsequent reporting, seven-year median overall survival was also improved (89 versus 84 percent, hazard ratio 0.66) [4]. For those with residual disease after neoadjuvant therapy for HER2-positive breast cancer, we administer T-DM1 in the adjuvant setting. (See "Adjuvant systemic therapy for HER2-positive breast cancer", section on 'T-DM1'.)

Frequency of mammographic surveillance in patients aged ≥50 years with breast cancer (February 2025)

There are limited data regarding the frequency of mammographic surveillance in breast cancer survivors. In a randomized trial in 5235 patients age ≥50 years with a history of breast cancer, annual versus less frequent mammographic surveillance resulted in similar five-year breast cancer-specific survival rates (98.1 versus 98.3 percent) and overall survival rates (94.7 versus 94.5 percent) [5]. Most breast cancer events in both groups were detected from emergency admissions or referrals for symptoms. Although these results are promising, the follow-up for this trial was short. The majority of patients (83 percent) had estrogen receptor-positive disease, which often recurs later. We await further data before altering our practice related to frequency of mammographic screening of breast cancer survivors. (See "Approach to the patient following treatment for breast cancer", section on 'Mammography'.)

No role for adjuvant atezolizumab in triple-negative breast cancer (February 2025)

Trials investigating the role of immune checkpoint inhibitors in early triple-negative breast cancer (TNBC) have found a benefit of the inclusion of neoadjuvant pembrolizumab with chemotherapy for selected patients at risk of recurrence. By contrast, a recent randomized trial of atezolizumab added to adjuvant chemotherapy in patients with stage II to III TNBC who had completed surgery did not show improvements in recurrence rates or survival [6]. As such, we do not use adjuvant atezolizumab for early TNBC. (See "ER/PR-negative, HER2-negative (triple-negative) breast cancer", section on 'Choice of regimen, and inclusion of immunotherapy for selected patients'.)

Trastuzumab deruxtecan in hormone receptor-positive, HER2-low or ultralow breast cancer (September 2024, Modified February 2025)

Trastuzumab deruxtecan (T-DxD) has an expanding role in patients with hormone receptor-positive advanced breast cancer refractory to endocrine treatment, both for HER2-low (immunohistochemistry [IHC] 1+ or 2+ and in situ hybridization negative) and ultralow cancers (IHC 0 with membrane staining). In a randomized trial in 866 patients with hormone receptor-positive, HER2-low or ultralow disease who had received at least one line of endocrine based-therapy and no prior chemotherapy for metastatic disease, trastuzumab deruxtecan improved progression-free survival relative to chemotherapy (13.2 versus 8.1 months) [7]. Benefits were similar among patients with HER2-low and ultralow disease. Grade 3 or higher adverse events occurred in 53 and 44 percent of patients, respectively. Overall survival results are not yet mature. Based on these results, the US Food and Drug Administration has expanded approval of T-DxD to include patients with hormone receptor-positive, HER2-low or ultralow disease that has progressed on at least one line of endocrine therapy [7]. (See "Endocrine therapy resistant, hormone receptor-positive, HER2-negative advanced breast cancer".)

CDK 4/6 inhibitors in metastatic hormone receptor-positive, HER2-negative breast cancer (January 2025)

Although cyclin-dependent kinase inhibitors (CDK 4/6i) are typically used as initial therapy for metastatic hormone receptor (HR)-positive, HER2-negative breast cancer, studies are evaluating whether they can be deferred to second-line treatment, given their toxicities and financial burden. In a randomized trial in over 1000 patients receiving first-line treatment with a nonsteroidal aromatase inhibitor (NSAI), followed by fulvestrant as second-line treatment, those assigned to receive a CDK 4/6i with first-line treatment experienced a median overall survival of 46 months versus 54 months among those assigned to receive it with second-line treatment (HR 0.98, 95% CI 0.80-1.20) [8]. Although we typically incorporate CDK 4/6 inhibitors with initial therapy for metastatic HR-positive, HER2-negative breast cancer, deferral to the second line is a possible alternative for selected patients (eg, those with endocrine-sensitive disease [ie, metastatic recurrence occurred >12 months from adjuvant endocrine therapy]) who prefer to avoid initial treatment with a CDK 4/6 inhibitor. (See "Treatment for hormone receptor-positive, HER2-negative advanced breast cancer", section on 'Alternative frontline options'.)

Datopotamab deruxtecan in hormone receptor-positive, HER2-negative breast cancer (January 2025)

Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell surface antigen 2-directed antibody-drug conjugate that has been studied in advanced hormone receptor-positive (HR+), HER2-negative breast cancer. In a randomized trial among 732 adult patients who had previously received treatment with endocrine therapy and one to two lines of chemotherapy for such cancers, Dato-DXd improved progression-free survival relative to investigator's choice of chemotherapy (hazard ratio 0.63), but differences in overall survival were not statistically significant [9]. Grade ≥3 toxicities were lower with Dato-DXd (21 versus 45 percent). Based on these data, Dato-DXd has regulatory approval in the United States for adult patients with unresectable or metastatic, HR+, HER2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease [10], and we agree with its use in this setting. (See "Endocrine therapy resistant, hormone receptor-positive, HER2-negative advanced breast cancer", section on 'Datopotamab deruxtecan'.)

Air pollution and breast cancer (January 2025)

Studies are evaluating whether an association exists between breast cancer and environmental factors such as air pollution. In a meta-analysis including 11 cohort studies, there was a modest trend toward an increase in breast cancer incidence associated with a 10 mcg/m3 increase in exposure to fine particulate matter (hazard ratio [HR] 1.05), but it did not reach statistical significance [11]. Given available data, there is no clear association between air pollution and breast cancer. (See "Factors that modify breast cancer risk in females", section on 'Air pollution'.)

Role of surgery in hormone receptor-positive ductal carcinoma in situ (January 2025)

Trials are evaluating whether surgery can be omitted in some patients with ductal carcinoma in situ (DCIS). In a randomized trial in 995 patients with hormone receptor-positive grade 1 or 2 DCIS, those assigned to active monitoring (follow-up every six months with breast imaging and physical exam) experienced similar rates of ipsilateral breast cancer as those assigned to surgery (4.2 versus 5.9 percent) [12]. However, follow-up was short (median 37 months) and many patients (40 percent) did not accept their assigned treatment. Although these results are promising that de-escalation may be appropriate in selected patients, further data are necessary prior to routine use of this approach. (See "Ductal carcinoma in situ: Treatment and prognosis", section on 'Investigative approach'.)

Nab-paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (January 2025)

Trials are evaluating ways to safely de-escalate treatment among patients with early HER2-positive breast cancer. In a randomized trial in 689 such patients, neoadjuvant nab-paclitaxel was compared with the standard regimen of docetaxel plus carboplatin; all patients also received trastuzumab and pertuzumab [13]. While the nab-paclitaxel group experienced higher rates of pathological complete response (66 versus 58 percent) and fewer grade 3/4 adverse events (30 versus 38 percent), long-term survival outcomes are not yet available. In addition, the trial was conducted in China, which may affect the generalizability of the findings. We await further data prior to routine use of nab-paclitaxel, trastuzumab, and pertuzumab as a neoadjuvant regimen in HER2-positive breast cancer. (See "Neoadjuvant therapy for patients with HER2-positive breast cancer", section on 'Treatment de-escalation'.)

Role of sentinel lymph node biopsy in early breast cancer (December 2024)

Whether selected patients with low-risk early breast cancers can safely omit sentinel node biopsy (SLNB) is unclear. In a randomized trial including nearly 5000 patients with clinically node-negative invasive breast cancers ≤5 cm scheduled to undergo breast conserving surgery, the "no axillary surgery" group experienced the same five-year invasive disease-free survival rate as the SLNB group (92 percent) [14]. Most patients had T1 cancers. While outcomes from this trial are promising, we await longer-term outcomes before omitting SLNB in early breast cancer. (See "Overview of management of the regional lymph nodes in breast cancer", section on 'Can ultrasound identify patients who can omit sentinel node biopsy?'.)

Inavolisib in hormone receptor-positive, HER2-negative breast cancer (November 2024)

Trials are evaluating novel treatment strategies in those with advanced hormone receptor (HR)-positive/HER2-negative breast cancer with endocrine therapy-resistant disease, with promising results among those with PIK3CA-mutated cancers. In a randomized trial in 325 such patients who experienced recurrence on or within 12 months of adjuvant endocrine therapy, the addition of the alpha isoform-specific PI3K inhibitor and degrader inavolisib to fulvestrant and palbociclib improved progression-free survival (15 versus 7.3 months) [15]. There was a trend favoring overall survival that did not reach statistical significance, although survival data are immature (hazard ratio 0.64). Grade ≥3 adverse events occurred in 88 versus 82 percent. For patients with locally advanced or metastatic, endocrine therapy-resistant PIK3CA-mutated, HR-positive, HER2-negative breast cancer, we consider the combination of inavolisib with palbociclib and fulvestrant to be appropriate option, which now has regulatory approval in the United States [16]. (See "Treatment for hormone receptor-positive, HER2-negative advanced breast cancer", section on 'Alterations in the PI3K pathway'.)

GASTROINTESTINAL CANCER

Tislelizumab plus chemotherapy for metastatic esophageal squamous cell carcinoma (April 2025)

Tislelizumab, a PD-1 inhibitor, has been approved by the US Food and Drug Administration in combination with platinum-containing chemotherapy for the first-line treatment of advanced unresectable or metastatic esophageal squamous cell carcinoma (SCC) that expresses PD-L1 (≥1) [17]. This approval is based on the results of a randomized trial in which almost 500 such patients with a combined positive score (CPS) ≥1 experienced improved overall survival (OS) with the addition of tislelizumab to chemotherapy (median 17 versus 10 months) and had few side effects [18]. Based on these data, we consider tislelizumab plus chemotherapy to be an appropriate option for initial therapy for patients with advanced unresectable or metastatic esophageal SCC and CPS ≥1. (See "Initial systemic therapy for metastatic esophageal and gastric cancer", section on 'Tislelizumab plus chemotherapy'.)

Nivolumab plus ipilimumab for mismatch repair-deficient metastatic colorectal cancer (March 2025)

For patients with metastatic colorectal cancer (mCRC) that is mismatch repair deficient (dMMR)/with high levels of microsatellite instability (MSI-H), there is interest in combination immunotherapy (ie, nivolumab plus ipilimumab). In a phase III trial of approximately 700 patients with dMMR/MSI-H mCRC, at median follow-up of 47 months, nivolumab plus ipilimumab improved progression-free survival over nivolumab alone (median 54 versus 18 months) with an acceptable toxicity profile [19]. For patients with dMMR/MSI-H mCRC, we suggest initial therapy with nivolumab plus ipilimumab. (See "Initial systemic therapy for metastatic colorectal cancer", section on 'Nivolumab plus ipilimumab'.)

Immunotherapy and antiangiogenic therapy plus transarterial chemoembolization for localized non-metastatic hepatocellular carcinoma (February 2025)

In patients with localized unresectable hepatocellular carcinoma (HCC) without distant metastases, studies are evaluating the addition of immunotherapy and antiangiogenic agents to transarterial chemoembolization (TACE). In separate randomized trials of patients with localized non-metastatic HCC, the addition of three separate regimens of immunotherapy and antiangiogenic therapy to TACE improved progression-free survival (median 15 versus 10 months for lenvatinib plus pembrolizumab; median 15 versus 8 months for durvalumab plus bevacizumab; median 11 versus 3 months for camrelizumab plus apatinib) but increased toxicity [20-22]. Further data, including overall survival outcomes, are necessary prior to incorporating the combination of immunotherapy, antiangiogenic therapy, and TACE into the routine clinical management of localized unresectable non-metastatic HCC. (See "Localized hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates not eligible for local thermal ablation", section on 'Systemic therapy plus TACE versus TACE alone'.)

Overall survival for pembrolizumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric and esophageal adenocarcinoma (February 2025)

Patients with metastatic gastric and esophageal adenocarcinoma that is HER2-positive and expresses programmed cell death ligand 1 (PD-L1) are treated with the combination of pembrolizumab, trastuzumab, and chemotherapy, but long-term data on overall survival (OS) were not previously reported. In extended follow-up (median of 50 months) of a phase III trial of approximately 700 patients with previously untreated, HER2-positive advanced gastroesophageal adenocarcinoma, the addition of pembrolizumab to trastuzumab and fluoropyrimidine plus platinum-based chemotherapy improved OS in the entire study population (median 20 versus 17 months) and those with a combined positive score (CPS) >1 (median 20 versus 16 months) [23]. For patients with advanced unresectable or metastatic HER2-positive gastric and esophageal adenocarcinoma and CPS >1, we continue to recommend the addition of pembrolizumab to trastuzumab and chemotherapy. (See "Initial systemic therapy for metastatic esophageal and gastric cancer", section on 'Pembrolizumab plus trastuzumab and chemotherapy'.)

FOLFOX plus cetuximab and encorafenib for metastatic colorectal cancer (January 2025, Modified February 2025)

For patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC), there is interest in using novel treatment approaches, such as encorafenib (a BRAF inhibitor) in combination with cetuximab (an epidermal growth factor receptor [EGFR] inhibitor). In a randomized trial of almost 500 patients with mCRC, at median follow-up of ten months, initial systemic therapy with FOLFOX plus cetuximab and encorafenib improved one-year overall survival (80 versus 66 percent) and objective response rates (61 versus 40 percent) compared with oxaliplatin-based chemotherapy with or without bevacizumab [24]. Based on these data, the US Food and Drug Administration approved encorafenib in combination with cetuximab and FOLFOX for the treatment of mCRC with a BRAF V600E mutation [25], and we recommend initial therapy with this combination. (See "Initial systemic therapy for metastatic colorectal cancer", section on 'RAS wild-type, BRAF V600E-mutant tumors'.)

Zolbetuximab plus chemotherapy for advanced esophageal and gastric adenocarcinoma (January 2025)

For patients with advanced esophageal and gastric cancer, studies are evaluating novel targeted agents, such as zolbetuximab, an antibody against the protein Claudin 18.2 (CLDN18.2). In a combined analysis of two separate randomized trials with over 1000 patients with unresectable, HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, the addition of zolbetuximab to chemotherapy improved overall survival (HR 0.77) [26]. Based on these data, zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy was approved by the US Food and Drug Administration for initial treatment of locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma that is CLDN18.2 positive [17]. Given other data showing benefit for immunotherapy in those with high combined positive scores (CPS), we consider both CLDN18.2 expression and CPS in choosing whether to pair zolbetuximab versus immunotherapy with chemotherapy in patients with advanced HER2-negative esophageal and gastric adenocarcinoma. (See "Initial systemic therapy for metastatic esophageal and gastric cancer", section on 'Zolbetuximab plus chemotherapy'.)

Tislelizumab plus chemotherapy for metastatic gastric and esophageal adenocarcinoma (January 2025)

Tislelizumab, a PD-1 inhibitor, has been approved by the US Food and Drug Administration in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma that expresses PD-L1 (≥1) [17]. This approval is based on the results of a randomized trial in which the addition of tislelizumab to chemotherapy improved overall survival (OS) in approximately 1000 patients with such cancers regardless of PD-L1 expression status; however, this OS benefit was mostly driven by those with a combined positive score (CPS) ≥5. Based on these data, we consider tislelizumab plus chemotherapy to be an appropriate option for initial therapy for patients with advanced HER2-negative gastric and esophageal adenocarcinoma and CPS ≥5. (See "Initial systemic therapy for metastatic esophageal and gastric cancer", section on 'Tislelizumab plus fluorouracil and platinum'.)

Zanidatamab for HER2-positive metastatic biliary tract cancers (December 2024)

For patients with advanced or metastatic HER2-positive biliary tract cancers (cholangiocarcinoma and gallbladder cancer), there is interest in novel therapies such as zanidatamab, a bispecific antibody that targets two distinct HER2 epitopes. In a phase II trial of 80 patients with advanced or metastatic HER2-positive biliary tract cancers who progressed on gemcitabine-based therapy and had no prior exposure to HER2-targeted therapy, zanidatamab demonstrated an objective response rate of 41 percent and was well tolerated [27]. Based on these data, the US Food and Drug Administration granted accelerated approval to zanidatamab for adult patients with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, and we consider it to be an acceptable option in this population. (See "Systemic therapy for advanced unresectable and metastatic cholangiocarcinoma", section on 'Zanidatamab'.)

Neoadjuvant therapy for locally advanced resectable esophageal squamous cell carcinoma (November 2024)

In patients with locally advanced resectable thoracic esophageal squamous cell carcinoma (SCC), studies are comparing neoadjuvant chemotherapy with neoadjuvant chemoradiation (CRT) prior to surgery. In a randomized trial in over 600 such patients, three-year overall survival for neoadjuvant triplet chemotherapy compared with neoadjuvant CRT (both followed by esophagectomy) was 72 versus 68 percent, but the difference was not statistically significant [28]. Relative to neoadjuvant CRT, neoadjuvant chemotherapy resulted in higher rates of treatment discontinuation (9 versus 6 percent). For most patients with clinical T3 to T4 or node-positive esophageal SCC that is resectable, we continue to suggest initial therapy with CRT, followed by evaluation for surgery. However, neoadjuvant or perioperative chemotherapy is an acceptable alternative. (See "Neoadjuvant and adjuvant therapy for locally advanced resectable thoracic esophageal cancer", section on 'Chemotherapy versus chemoradiation'.)

Zenocutuzumab for advanced pancreatic or NSCLC cancers with an NRG1 fusion (December 2024, Modified February 2024)

The US Food and Drug Administration has approved the bispecific HER2- and HER3-directed antibody zenocutuzumab for two types of NRG1 fusion-positive advanced malignancies progressive on prior therapy; pancreatic adenocarcinoma and non-small cell lung cancer (NSCLC) [29]:

●In an open-label phase II trial that included 36 patients with advanced or metastatic NRG1-fusion positive pancreatic adenocarcinoma who progressed on prior systemic therapy, the objective response rate was 42 percent, with a median duration of response of seven months [30]. In the same study, in a subset of 93 patients with NSCLC, the response rate was 29 percent with a median duration of response of 12.7 months.

●Treatment-related grade ≥3 toxicities occurred in 7 percent of patients and included anemia, nausea, diarrhea, vomiting, abdominal pain, and elevated AST or ALT (1 percent or less for each).

We agree with the use of zenocutuzumab in these settings. (See "Second- and later-line systemic therapy for metastatic exocrine pancreatic cancer", section on 'NRG1 fusion-positive tumors' and "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'NRG1 fusions'.

GENITOURINARY ONCOLOGY

Nivolumab-hyaluronidase for advanced renal cell carcinoma (March 2025)

There is interest in the use of nivolumab-hyaluronidase, a subcutaneous form of nivolumab, in cancers such as renal cell carcinoma (RCC) to reduce drug preparation and administration time. In a randomized trial of almost 500 patients with treatment-refractory advanced or metastatic clear cell RCC and no prior immunotherapy, nivolumab-hyaluronidase demonstrated similar pharmacokinetics and objective response rates relative to intravenous (IV) nivolumab (24 versus 18 percent) [31]. Based on these data, the United States Food and Drug Administration approved nivolumab-hyaluronidase in patients with advanced RCC that is intermediate or poor risk as maintenance therapy following combination IV nivolumab plus ipilimumab as well as those with advanced RCC who received prior antiangiogenic therapy [17]. (See "Systemic therapy for advanced and metastatic clear cell renal cell carcinoma", section on 'Nivolumab-hyaluronidase (subcutaneous)'.)

Standard versus extended lymphadenectomy for bladder cancer (January 2025)

The optimal extent of pelvic lymphadenectomy for bladder cancer is debated. In a recent randomized trial including nearly 600 patients with cT2-4a N0-2 bladder cancer, extended lymphadenectomy resulted in more lymph nodes removed, more severe complications, and more deaths within 90 days compared with standard lymphadenectomy [32]. However, rates of nodal metastasis, five-year disease-free survival, and overall survival were similar. Based on these data, we suggest standard lymphadenectomy for localized muscle-invasive bladder cancer. (See "Radical cystectomy", section on 'Lymphadenectomy'.)

Lack of overall survival benefit for sacituzumab govitecan in metastatic urothelial carcinoma (December 2024)

Sacituzumab govitecan, an antibody-drug conjugate, initially received accelerated approval from the US Food and Drug Administration (FDA) for patients with advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and immunotherapy. However, in a randomized trial of over 700 such patients, sacituzumab govitecan failed to improve overall survival over chemotherapy [33]. Based on these data, the FDA withdrew regulatory approval for sacituzumab govitecan for the above indications [17], and we also no longer use it as later-line treatment of mUC. (See "Treatment of metastatic urothelial carcinoma of the bladder and urinary tract", section on 'No role for sacituzumab govitecan'.)

GYNECOLOGIC ONCOLOGY

Sexual dysfunction after simple versus radical hysterectomy for early-stage cervical cancer (February 2025)

For selected patients with early-stage cervical cancer, simple rather than radical hysterectomy (both with lymph node assessment) has become the preferred type of surgery, as less extensive surgery decreases surgical morbidity with similar oncologic outcomes. In a randomized trial evaluating 700 patients with early-stage cervical cancer, compared with radical hysterectomy, simple hysterectomy also resulted in lower rates of sexual dysfunction (based on sexual worry, enjoyment, activity, and vaginal functioning) for up to 24 months but rates were similar at 36 months [34]. These findings are useful when counseling patients with early-stage cervical cancer prior to hysterectomy. (See "Management of early-stage cervical cancer", section on 'Sexual dysfunction'.)

Heated intraperitoneal chemotherapy for platinum-sensitive relapsed ovarian cancer (January 2025)

Given the tendency of recurrent epithelial ovarian cancer (EOC) to present as abdominal disease, there is interest in heated intraperitoneal chemotherapy (HIPEC) for women with recurrent EOC following surgical cytoreduction.

●In an open-label randomized trial in 415 patients with platinum-sensitive relapse, after six cycles of platinum-based chemotherapy (and optional bevacizumab), the HIPEC group had a better median overall survival than the no HIPEC group (54 versus 46 months), but also more grade ≥3 toxicities (49 versus 27 percent) [35].

●In a trial among 167 patients with platinum-sensitive relapse proceeding directly to surgery (ie, no neoadjuvant therapy), median progression-free survival was 23 months in the group that underwent surgery alone and 25 months in the group that underwent cytoreductive surgery with HIPEC, a difference that was not statistically significant [36].

We do not routinely administer HIPEC for platinum sensitive relapse; however, we recognize that some centers offer HIPEC in this setting for patients who have undergone neoadjuvant chemotherapy. If HIPEC is considered, careful discussion about its toxicities should be individually addressed with patients. (See "Medical treatment for relapsed epithelial ovarian, fallopian tube, or peritoneal cancer: Platinum-sensitive disease".)

NEUROONCOLOGY

GD2-CAR-T cell therapy in H3K27M-mutant diffuse midline glioma (January 2025)

Novel immune therapies are under investigation for diffuse midline gliomas (DMG) including diffuse intrinsic pontine glioma (DIPG), a deadly form of childhood brain cancer with a median survival of less than one year. In a phase 1 trial of chimeric antigen receptor-T (CAR-T) cell therapy targeting the GD2 antigen, 11 patients with H3 K27M-mutant DMG (9 with DIPG) were treated with intravenous (IV) GD2-CAR-T cell infusion; 9 patients also received intracerebroventricular (ICV) infusions [37]. More than half of the patients exhibited volumetric tumor reductions and neurologic improvement, although most patients had recently completed radiation therapy, complicating response attribution. Two patients were alive 30 and 33 months after first infusion, respectively, including one with an ongoing complete response. Further study of these promising but preliminary results is ongoing. (See "Diffuse intrinsic pontine glioma", section on 'Investigational therapies'.)

SOFT TISSUE AND BONE TUMORS

Pembrolizumab for Kaposi sarcoma (April 2025)

Studies are investigating second line systemic therapy options for patients with AIDS-related Kaposi sarcoma (KS). In a trial of 32 patients most of whom had already received first line therapy, treatment with pembrolizumab demonstrated a response rate of 62 percent [38]. However, one patient died from treatment related complications and 25 percent of patients required systemic steroids due to toxicity. While pembrolizumab is an option for second-line therapy, we typically prefer paclitaxel due to a likely more favorable balance of risks and benefits. (See "AIDS-related Kaposi sarcoma: Staging and treatment", section on 'Pembrolizumab'.)

Vimseltinib for tenosynovial giant cell tumor (March 2025)

Vimseltinib, a tyrosine kinase inhibitor, has been approved by the US Food and Drug Administration for patients with tenosynovial giant cell tumor (TGCT) for whom additional surgery would cause functional limitations or severe morbidity [39]. It was approved based on an earlier placebo-controlled randomized trial that demonstrated an objective response rate of 40 percent in such patients [40]. In the trial there were no cases of drug-induced liver injury or potentially fatal hepatotoxicity, which has been observed with pexidartinib, an alternative agent for TGCT. We now suggest vimseltinib instead of pexidartinib for adult patients with TGCT. (See "Treatment for tenosynovial giant cell tumor and other benign neoplasms affecting soft tissue and bone", section on 'Vimseltinib (preferred)'.)

Neoadjuvant pembrolizumab for undifferentiated pleomorphic sarcoma (December 2024)

The role of neoadjuvant and adjuvant systemic therapy for soft tissue sarcoma of the extremities is unclear. In a recent study of patients with soft tissue sarcoma, most of whom had grade 2 or 3, stage III undifferentiated pleomorphic sarcoma (UPS) of the extremity, the addition of neoadjuvant and adjuvant pembrolizumab to preoperative radiotherapy and surgery improved two-year disease-free survival (67 versus 52 percent) [41]. The incidence of grade ≥3 adverse events was higher in the pembrolizumab group (56 versus 31 percent). We now consider this regimen as an option for patients with UPS. However, given limited follow-up and an unknown impact on survival, the decision about whether to use immunotherapy should involve shared decision-making. (See "Adjuvant and neoadjuvant systemic therapy for soft tissue sarcoma of the extremities", section on 'Neoadjuvant PD-1-based immunotherapy for undifferentiated pleomorphic sarcoma'.)

THORACIC ONCOLOGY

Tumor, Node, Metastasis staging for thoracic cancers (ninth version) (February 2025, Modified March 2025)

The American Joint Commission on Cancer has revised the Tumor, Node, Metastasis (TNM) staging system for a number of cancers [42]. Notable revisions for thoracic cancers include changes to nodal staging in lung cancer (table 1), such that there is now a division of N2 disease into N2a (tumor involvement of a single ipsilateral mediastinal nodal station or of the subcarinal nodal station) and N2b (tumor involvement of multiple ipsilateral mediastinal nodal stations). Revisions have also been made in the staging of pleural mesothelioma (table 2) as well as thymic tumors (table 3). (See "Clinical presentation, diagnosis, and staging of thymoma and thymic carcinoma", section on 'Staging system' and "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer", section on 'Staging'.)

American College of Chest Physicians guidelines on management of central airway obstruction (February 2025)

The American College of Chest Physicians has published its first consensus guideline on the management of central airway obstruction [43]. It promotes the use of therapeutic rigid (rather than flexible) bronchoscopy, general anesthesia, and local ablative therapies to achieve immediate airway patency. The guideline recommends airway dilation in patients undergoing therapeutic bronchoscopy who have stenotic, nonmalignant central airway obstruction, and stent placement for patients with symptomatic malignant or nonmalignant central airway obstruction, after other modalities have failed. The guideline also recommends curative surgical resection, when feasible. We agree with these recommendations. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults" and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Introduction'.)

Nonsurgical biopsy modalities for peripheral pulmonary nodules (December 2024)

The optimal non-open surgical biopsy modality for peripheral pulmonary nodules (PPNs) is unclear. One recent network meta-analysis reported that computed tomography (CT)-guided transbronchial needle aspiration (CT-TBNA) had the highest diagnostic yield (89 percent), followed by robot-assisted bronchoscopy (RAB; 85 percent) and radial endobronchial ultrasound (rEBUS; 72 percent) [44]. However, CT-TBNA had the highest rate of pneumothorax requiring chest tube drainage (1.6 percent versus <1 percent for RAB or rEBUS) and bleeding (5.2 percent versus <1.5 percent RAB or rEBUS). This study summarizes two important factors that we take into consideration when choosing a non-open surgical biopsy modality for PPNs. Additional factors include PPN location and local expertise. (See "Image-guided bronchoscopy for biopsy of peripheral pulmonary lesions", section on 'Image-guided bronchoscopy techniques'.)

Zenocutuzumab for advanced pancreatic or NSCLC cancers with an NRG1 fusion (December 2024, Modified February 2024)

The US Food and Drug Administration has approved the bispecific HER2- and HER3-directed antibody zenocutuzumab for two types of NRG1 fusion-positive advanced malignancies progressive on prior therapy; pancreatic adenocarcinoma and non-small cell lung cancer (NSCLC) [29]:

●In an open-label phase II trial that included 36 patients with advanced or metastatic NRG1-fusion positive pancreatic adenocarcinoma who progressed on prior systemic therapy, the objective response rate was 42 percent, with a median duration of response of seven months [30]. In the same study, in a subset of 93 patients with NSCLC, the response rate was 29 percent with a median duration of response of 12.7 months.

●Treatment-related grade ≥3 toxicities occurred in 7 percent of patients and included anemia, nausea, diarrhea, vomiting, abdominal pain, and elevated AST or ALT (1 percent or less for each).

We agree with the use of zenocutuzumab in these settings. (See "Second- and later-line systemic therapy for metastatic exocrine pancreatic cancer", section on 'NRG1 fusion-positive tumors' and "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'NRG1 fusions'.

MISCELLANEOUS TUMORS

Site-specific treatment guided by MCCA for cancer of unknown primary (October 2024)

For patients with cancer of unknown primary site (CUP), management strategies are evolving to incorporate molecular cancer classifier assays (MCCAs) to predict the tissue of origin as well as comprehensive molecular profiling (CMP) to identify targetable molecular alterations. In a randomized trial of nearly 200 patients with previously untreated metastatic CUP, at median follow-up of 33 months, site-specific therapy (as directed by MCCA) improved progression-free survival (PFS) compared with empiric chemotherapy (median 10 versus 7 months) [45]. In another randomized trial of almost 500 patients with previously untreated metastatic CUP who did not have MCCAs performed, at median follow-up of 24 months, the addition of molecularly guided therapy directed by CMP to empiric chemotherapy improved PFS (median 6 versus 4 months) [46]. Based on these results, for patients in whom neither the clinical nor pathologic evaluation suggests a primary site, we offer site-specific therapy based on MCCA. For those in whom MCCA fails to predict a tissue of origin (or is not obtained), we offer the addition of molecularly guided therapy as directed by CMP to empiric chemotherapy. (See "Adenocarcinoma of unknown primary site", section on 'Patients not in specific clinicopathologic subgroups'.)