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BACKGROUND: Prior research has demonstrated a discrepancy between pathologic and clinical staging in individuals with muscle-invasive bladder cancer (MIBC) following neoadjuvant chemotherapy (NAC). These findings were the major reasons for the under-usage of the bladder preservation strategy. Hence, we aim to explore the reliable markers in identifying pathological complete response (ypCR) status in MIBC patients who achieved clinical complete response (cCR) after NAC. METHODS: Between January 2016 and April 2023, 161 consecutive MIBC patients treated with NAC and achieved cCR were enrolled in the study. Patient clinicopathologic information was documented. Multivariate binary logistic regression was used for determining adjusted odds ratios (OR) and 95% confidence intervals (CI). It considered statistically significant when a P < .05. RESULTS: Of the 161 MIBC patients with cCR after NAC, 64.0% (103/161) achieved ypCR after RC. The independent factors for ypCR status were the origin of MIBC (secondary vs. Primary) with odds ratios (OR) of 0.433 (P = .027), the pathological type (pure vs. mixed) with OR of 3.556 (P = .003), concurrent carcinoma in situ (yes vs. no) with OR of 0.360 (P = .016), and lymphovascular invasion (yes vs. no) with OR of 0.271 (P = .007). CONCLUSION: This study demonstrated that primary MIBC, pure UC pathological type, absence of concurrent CIS, and LVI were significant predictors of ypCR in MIBC patients who achieved cCR after NAC and before surgery. These findings may contribute to the decision-making process of bladder preservation strategy in selected patients.

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BACKGROUND: There is a paradigm shift in the management of locally advanced rectal cancer (LARC) from conventional neoadjuvant treatment to total neoadjuvant therapy (TNT). Despite its growing acceptance, there are limited studies that have examined its effects on disease presentation. In addition, it is important to determine the factors that play a role in complete response (CR). Our previous data from 119 patients revealed that the CR rate was 37%, and low rectal tumors and the absence of extramural vascular invasion (EMVI) were predictors of CR. Unfortunately, there continues to be a lack of data, and reliable markers are still needed to consistently identify the best respondents. Therefore, this study aimed to determine the factors associated with CR. Moreover, this study hypothesized that both predictive factors and the CR ratio might evolve over time because of the growing patient population. METHODS: This retrospective study included patients who completed TNT for LARC at our tertiary care center between 2015 and 2022. The primary outcome was to determine the predictors of CR. The secondary outcomes were the 2-year disease-free survival (DFS) rate and overall survival (OS) rate. CR consists of patients who sustained clinical CR (cCR) for at least 12 months under watch and wait or had pathologic CR (pCR) after surgery. RESULTS: Of 339 patients with LARC, 208 (61.3%) successfully completed TNT. Among 208 patients, 57 (27.4%) achieved cCR, and 166 (80.0%) sustained cCR without tumor regrowth after 1 year. The remaining 151 patients (72.6%) underwent surgery, and 42 patients had pCR. The final CR rate was 42.3%. The median age of the patients was 56 years (IQR, 49-66). Moreover, 132 participants (63.5%) were male, whereas 76 participants (36.5%) were female. The median tumor size was 4.95 cm (IQR, 3.60-6.43), with most tumors in the low rectum (119 [57.2%]). Based on the MRI findings, the mesorectal facia (MRF) involvement rate was 25.0% (n = 52), and EMVI was observed in 43 patients (20.7%). Low rectal tumors, the absence of MRF involvement, and the absence of EMVI were predictors of CR. With a median follow-up of 24.7 months, 2-year DFS and OS were significantly higher among patients with CR than among patients with incomplete response (91.3% vs 71.0% [P < .01] and 98.8% vs 90.2% [P = .03], respectively). CONCLUSION: An increasing CR rate was observed in our updated dataset compared with that in our previous study. In addition to previously identified predictors, low tumor location, and the absence of EMVI, the absence of MRF involvement was determined as a predictor of CR. Our findings offer valuable insights into clinical practice and help clinicians set clear expectations when counseling patients.

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BACKGROUND: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. METHODS: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . DISCUSSION: Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Fluorouracilo , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/mortalidad , Neoplasias del Recto/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante/métodos , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Masculino , Femenino , Supervivencia sin Enfermedad , Leucovorina/administración & dosificación , Leucovorina/uso terapéutico , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Irinotecán/administración & dosificación , Irinotecán/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Calidad de Vida , Estadificación de Neoplasias , Compuestos Organoplatinos

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Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.(AU)

Asunto(s)

Humanos , Masculino , Femenino , Recurrencia Local de Neoplasia , Terapia Neoadyuvante/métodos , Resultado del Tratamiento , Quimioradioterapia/métodos

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Background: Standardized assessments of clinical complete response (cCR) to neoadjuvant chemoradiotherapy (nCRT) for rectal cancer have been established, but their utility and accuracy remain unclear. This study aimed to evaluate the clinical diagnostic value of rectal magnetic resonance imaging (MRI) and endorectal ultrasonography (ERUS) for the determination of cCRs after neoadjuvant immunotherapy and to investigate the concordance between cCR and pathological complete response (pCR). Methods: Ninety-four patients with rectal cancer treated with neoadjuvant radiotherapy with or without immunotherapy were included. The sensitivity, specificity, and accuracy of each evaluation method were calculated. Results: Combined MRI and ERUS assessments found cCR in seven of the 94 patients in our cohort. In the non-immunotherapy group, the sensitivity, specificity, and accuracy of MRI for diagnosing cCR were 50.0%, 85.2%, and 77.1%, respectively, whereas those of ERUS were 50.0%, 92.6%, and 82.9%, respectively; those of combined MRI and ERUS were 25.0%, 96.3%, and 87.5%, respectively. In the immunotherapy group, the sensitivity, specificity, and accuracy with which MRI identified CR were 51.7%, 76.7%, and 64.4%, respectively; those of ERUS were 13.8%, 90.0%, and 52.5%, respectively, and those of combined MRI and ERUS were 10.3%, 96.7%, and 54.2%, respectively. We also found that 32 of 37 patients with pCR did not meet the cCR evaluation criteria. Of these pCR patients, 78.4% (29/37) received immunotherapy. In the entire cohort, there were five pCRs among the seven cCRs. Of the four cCRs that occurred in the immunotherapy group, three were pCRs. Conclusions: Rectal MRI and/or ERUS did not provide sufficiently accurate assessments of cCR in patients with rectal cancer receiving neoadjuvant therapy, especially immunotherapy, and cCR did not predict pCR.

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In patients with advanced lung adenocarcinoma (LADC) harboring the echinoderm microtubule-associated protein-like 4 (EML4) -anaplastic lymphoma kinase (ALK) rearrangement, targeted therapy typically demonstrates superior efficacy as an initial treatment compared to chemotherapy. Following resistance to ALK-tyrosine kinase inhibitors (TKIs), regimens incorporating platinum-based dual agents or combined with bevacizumab often show effectiveness. However, therapeutic alternatives become constrained after resistance develops to both TKIs and platinum-based therapies. Given that the majority of ALK-positive non-small cell lung carcinomas (NSCLC) are LADC, the benefits of TKIs for patients with ALK-positive lung squamous cell carcinoma (LSCC) and the optimal treatment strategy for these patients remain a subject of debate. In this case study, we report on a patient with advanced LSCC, in whom the EML4-ALK rearrangement was identified via ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction). The patient underwent oral treatment with crizotinib and alectinib, showing effectiveness in both first-line and second-line ALK-TKI therapies, albeit with limited progression-free survival (PFS). Subsequent resistance to second-generation TKI was followed by the detection of tumors in the left neck region via computed tomography (CT). Biopsy pathology revealed non-squamous cell carcinoma, and subsequent treatment with platinum-based double-drug therapy proved ineffective. Further analysis through next-generation sequencing (NGS) indicated ALK negativity but a high expression of programmed death-ligand 1 (PD-L1). Immunotherapy was then initiated, resulting in a PFS of over 29 months and clinical complete remission (cCR). This case underscores the potential benefit of ALK-TKIs in patients with ALK-positive LSCC. Resistance to second-generation TKIs may lead to ALK negativity and histological transformation, highlighting the necessity of repeated biopsies post-TKI resistance for informed treatment decision-making. As of November 2023, imaging studies continue to indicate cCR in the patient, with a survival time exceeding 47 months.

Asunto(s)

Adenocarcinoma del Pulmón , Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Quinasa de Linfoma Anaplásico/genética , Quinasa de Linfoma Anaplásico/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinasas , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Antineoplásicos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Inmunoterapia , Pulmón/patología

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Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the peritoneum with a poor prognosis and nonspecific clinical course. We discuss a case of MPeM in a 59-year-old male who presented with abdominal pain and distension, without any known previous asbestos exposure. The diagnosis was made after a second biopsy finally confirmed epithelioid MPeM in an advanced stage with pleural effusion. The patient underwent six cycles of chemotherapy with cisplatin and pemetrexed, experienced disease progression, and was then started on pembrolizumab as a second-line treatment. The patient achieved a complete response after two years of treatment with pembrolizumab and has been disease-free for almost four years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Despite the lack of evidence to support the treatment with immunotherapy for MPeM, our case report encourages its use, highlighting its ability to enable a complete response with pembrolizumab with an excellent quality of life.

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Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.

Asunto(s)

Neoplasias del Recto , Espera Vigilante , Humanos , Consenso , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Recto/patología , Terapia Neoadyuvante/métodos , Quimioradioterapia/métodos , Respuesta Patológica Completa , Resultado del Tratamiento

Asunto(s)

Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Recto , Neoplasias del Recto/terapia , Espera Vigilante , Quimioradioterapia , Resultado del Tratamiento , Recurrencia Local de Neoplasia/terapia

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The aim was to evaluate the efficacy and safety between the watch-and-wait strategy (WW), radical surgery (RS), and local excision (LE) for rectal cancer with clinical complete response (cCR) after neoadjuvant radiotherapy (nCRT). We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trials to compare WW with RS and LE for patients with cCR until March 2023 and collected the following data: local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), overall survival (OS), and disease-free survival (DFS). In total, 2240 patients from 21 studies were included. Pairwise meta-analysis revealed no statistically significant differences between the three groups in terms of CRD and 2-, 3-, and 5-year OS (P < 0.05). The RS group was significantly better than the WW group in terms of the LR rate (odds ratio [OR] = 0.12, 95 % confidence interval [CI]: 0.06-0.21, P < 0.001, I2 = 0 %], 3-year DFS (OR = 1.56, 95 % CI: 1.10-2.21, P = 0.01, I2 = 38 %), and 5-year DFS (OR = 2.30, 95 % CI: 1.53-3.46, P < 0.001, I2 = 34 %). The results of network meta-analysis were also similar. After sensitivity analysis, the 5-year OS of the RS group was significantly better than that of the WW group (OR = 2.77, 95 % CI: 1.28-6.00, P = 0.009, I2 = 33 %). Nevertheless, neither regression analysis nor subgroup analysis provided meaningful results. However, the cumulative meta-analysis of LR, DM, and 3- and 5-year DFS revealed significant turning points (P < 0.05). Our meta-analysis recommends using the WW strategy for patients with cCR having poor underlying conditions and high surgical risk; however, there is a risk of higher LR and worse survival after 3 years.

Asunto(s)

Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Metaanálisis en Red , Quimioradioterapia , Espera Vigilante/métodos , Recurrencia Local de Neoplasia , Neoplasias del Recto/cirugía , Resultado del Tratamiento

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Background: Short-course radiotherapy (SCRT) of 25 Gy in five daily fractions is a recommended strategy in the neoadjuvant setting for resectable locally advanced rectal cancer (LARC), as well as in cases of metastatic disease for local control. There is scarce information regarding the use of SCRT for patients who have received nonoperative management. Objectives: To describe the characteristics of patients who received treatment with SCRT for LARC and metastatic rectal cancer, toxicity, and the approach after radiation treatment. Methods: This is a retrospective analysis of all patients who underwent SCRT for rectal cancer at the Alexander Fleming Institute from March 2014 to June 2022. Results: In total, 44 patients were treated with SCRT. The majority were male (29, 66%), with a median age of 59 years (interquartile range 46-73). Most patients had stage IV disease (26, 59.1%), followed by LARC (18, 40.9%). Most lesions were located in the middle rectum (30, 68%). The majority of LARC patients underwent SCRT followed by consolidation chemotherapy (ChT) (16/18, 89%), while most patients with metastatic disease underwent SCRT followed by consolidation ChT (14/26, 53.8%). A clinical complete response (cCR) was documented in 8/44, 18.2% of patients. Most patients with LARC and cCR were managed by a watch and wait approach (5/18, 27.7%). Local recurrence was observed in LARC cases (2/18, 11.1%). Patients who underwent SCRT following consolidation ChT were more likely to have adverse events (AEs) than those undergoing induction ChT following SCRT (11/30, 36.7% versus 3/12, 25%, p = 0.02). Conclusion: In a subgroup of patients diagnosed with LARC and treated with SCRT followed by ChT, surgical treatment could be omitted after they achieved a cCR. Local recurrence was similar to that reported in a previous study. SCRT is a reasonable option for local disease control in stage IV disease, yielding low toxicity rates. Therefore, decisions must be made by a multidisciplinary team. Prospective studies are necessary to reach further conclusions.

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Objective: Examine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR). Methods: LARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded. Results: Twenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs. Conclusion: Neoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT.

Asunto(s)

Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Estudios de Cohortes , Estudios Retrospectivos , Resultado del Tratamiento , Reparación de la Incompatibilidad de ADN , Inestabilidad de Microsatélites , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/genética

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AIM: Neoadjuvant rectal (NAR) score is an early surrogate for longer-term outcomes in rectal cancer undergoing radiotherapy and resection. In an era of increasing organ preservation, resection specimens are not always available to calculate the NAR score. Post-treatment magnetic resonance imaging (MRI) re-staging of regression is subjective, limiting reproducibility. We explored the potential for a novel MRI-based NAR score (mrNAR) adapted from the NAR formula. METHODS: Locally advanced rectal cancer patients undergoing neoadjuvant therapy (nCRT) and surgery were retrospectively identified between 2008 and 2020 in a single cancer network. mrNAR was calculated by adapting the NAR formula, replacing pathological (p) stages with post-nCRT MR stages (ymr). Cox regression assessed relationships between clinicopathological characteristics, NAR and mrNAR with overall survival (OS) and recurrence-free survival (RFS). RESULTS: In total, 381 NAR and 177 mrNAR scores were calculated. On univariate analysis NAR related to OS (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.33-3.14, p = 0.001) and RFS (HR 2.52, 95% CI 1.77-3.59, p = 0.001). NAR 3-year OS <8 was 95.3%, 8-16 was 88.6% and >16 was 80%. mrNAR related to OS (HR 2.96, 95% CI 1.38-6.34, p = 0.005) and RFS (HR 2.99, 95% CI 1.49-6.00, p = 0.002). 3-year OS for mrNAR <8 was 96.2%, 8-16 was 92.4% and >16 was 78%. On multivariate analysis, mrNAR was a stage-independent predictor of OS and RFS. mrNAR corresponded to NAR score category in only 15% (positive predictive value 0.23) and 47.5% (positive predictive value 0.48) of cases for categories <8 and >16, respectively. CONCLUSIONS: Neoadjuvant rectal score is validated as a surrogate end-point for long-term outcomes. mrNAR categories do not correlate with NAR but have stage-independent prognostic value. mrNAR may represent a novel surrogate end-point for future neoadjuvant treatments that focus on organ preservation.

Asunto(s)

Neoplasias Primarias Secundarias , Neoplasias del Recto , Humanos , Terapia Neoadyuvante , Estudios Retrospectivos , Reproducibilidad de los Resultados , Pronóstico , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Quimioradioterapia , Quimioradioterapia Adyuvante , Biomarcadores , Imagen por Resonancia Magnética , Resultado del Tratamiento , Estadificación de Neoplasias

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BACKGROUND: Watch-and-wait strategy has been increasingly accepted for patients with clinical complete response (cCR) after multimodal treatment for locally advanced rectal adenocarcinoma. Close follow-up is essential to the early detection of local regrowth. It was previously demonstrated that probe-based confocal laser endomicroscopy (pCLE) scoring using the combination of epithelial and vascular features might improve the diagnostic accuracy of cCR. AIM: To validate the pCLE scoring system in the assessment of patients with cCR after neoadjuvant chemoradiotherapy (nCRxt) for advanced rectal adenocarcinoma. METHODS: Digital rectal examination, pelvic magnetic resonance imaging (MRI), and pCLE were performed in 43 patients with cCR, who presented either a scar (N = 33; 76.7%) or a small ulcer with no signs of tumor, and/or biopsy negative for malignancy (N = 10; 23.3%). RESULTS: Twenty-five (58.1%) patients were men, and the mean age was 58.4 years. During the follow-up, 12/43 (27.9%) patients presented local regrowth and underwent salvage surgery. There was an association between pCLE diagnostic scoring and final histological report (for patients who underwent surgical resection) or final diagnosis at the latest follow-up (p = 0.0001), while this association was not observed with MRI (p = 0.49). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 93.5%, 80%, 88.9%, and 86%, respectively. MRI sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 66.7%, 48.4%, 66.7%, 78.9%, and 53.5%, respectively. CONCLUSIONS: pCLE scoring system based on epithelial and vascular features improved the diagnosis of sustained cCR and might be recommended during follow-up. pCLE might add some valuable contribution for identifying local regrowth. Trial Registration This protocol was registered at the Clinical Trials (ClinicalTrials.gov identifier NCT02284802).

Asunto(s)

Adenocarcinoma , Neoplasias del Recto , Masculino , Humanos , Persona de Mediana Edad , Femenino , Terapia Neoadyuvante , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Terapia Combinada , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/terapia , Rayos Láser , Quimioradioterapia , Recurrencia Local de Neoplasia/diagnóstico , Espera Vigilante/métodos , Resultado del Tratamiento

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We report the case of a 65-year-old male diagnosed with advanced rectal cancer associated with necrotizing fasciitis (NF). Since radical surgery, total pelvic exenteration with sacrectomy, was rejected because of detrimental effects on quality of life, chemoradiotherapy (CRT) was chosen as anti-cancer treatment after urgent debridement. Although CRT was paused unintentionally just after delivering the total dose of radiation owing to the relapse of NF, the patient has maintained clinical complete response (cCR) without any distant metastasis for >5 years. Advanced rectal cancer is recognized as an NF risk factor. No definitive treatment strategies have been reported for NF-inducing rectal cancer; however, some reports have demonstrated curative extended surgery. Thus, CRT may be a less-invasive treatment option for NF-inducing rectal cancer, whereas severe adverse effects including re-infection after debridement should be closely monitored.

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BACKGROUND/AIM: Thanks to the promising benefits obtained in terms of quality of life, there has been growing interest in organ-sparing approaches after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer, mainly represented by transanal local excision and watch-and-wait. The main mandatory criterion is complete lymph nodal response (pN0). However, considering the reduced specificity of current radiological means in identifying one-to-one correspondence between clinical and pathological staging, the problem of underestimating lymph nodal involvement remains unsolved. The aim of this study was to identify the true percentage of patients eligible for conservative surgery and possible predictive factors. PATIENTS AND METHODS: Data for 59 patients with rectal cancer treated with nCRT followed by total mesorectal excision were analyzed. Patients with metastatic tumors and tumors treated with up-front surgery were excluded. Our primary endpoint was the pathological lymph nodal response rate after neoadjuvant chemoradiotherapy. The secondary endpoint was to identify predictive factors for lymph nodal response. RESULTS: The percentage of patients with pN0 was 62.71%, while in 37.28%, an organ-sparing approach would have not been oncologically correct. Parameters associated with pN0 were lower tumor size (T0-T2) (p=0.013) and lower grading (

Asunto(s)

Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Metástasis Linfática , Quimioradioterapia , Calidad de Vida , Estadificación de Neoplasias , Neoplasias del Recto/patología , Ganglios Linfáticos/patología , Estudios Retrospectivos

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The administration of neoadjuvant chemoradiotherapy (nCRT) followed by total mesorrectal excision (TME) and selective use of adjuvant chemotherapy can still be considered the standard of care in locally advanced rectal cancer (LARC). However, avoiding sequelae of TME and entering a narrow follow-up program of watch and wait (W&W), in select cases that achieve a comparable clinical complete response (cCR) to nCRT, is now very attractive to both patients and clinicians. Many advances based on well-designed studies and long-term data coming from big multicenter cohorts have drawn some important conclusions and warnings regarding this strategy. In order to safely implement W&W, it is important consider proper selection of cases, best treatment options, surveillance strategy and the attitudes towards near complete responses or even tumor regrowth. The present review offers a comprehensive overview of W&W strategy from its origins to the most current literature, from a practical point of view focused on daily clinical practice, without losing sight of the most important future prospects in this area.

RESUMEN

CONTEXT: Bladder-sparing strategies (BSSs) have been proposed for the treatment of muscle-invasive bladder cancer (MIBC) patients achieving clinical complete response (cCR) to initial systemic treatment to avoid toxicity related to radical cystectomy. OBJECTIVE: To systematically review the current literature evaluating oncological outcomes of BSSs in patients achieving cCR to initial systemic treatment for localized MIBC. EVIDENCE ACQUISITION: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting oncological outcomes of MIBC patients undergoing either surveillance or radiation therapy after achieving cCR to initial systemic treatment. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 23 noncomparative prospective or retrospective studies published between 1990 and 2021. The mean bladder and metastatic recurrence rates (range) as well as the mean bladder preservation rate (BPR; range) were calculated, and overall survival (OS) was extracted from included reports. EVIDENCE SYNTHESIS: Overall, 16 and seven studies evaluated surveillance (n = 610) and radiation therapy (n = 175) in MIBC patients achieving cCR to initial systemic treatment, respectively. With regard to surveillance, the median follow-up ranged from 10 to 120 mo, with a mean bladder recurrence rate of 43% (0-71%), including 65% of non-muscle-invasive bladder cancer (NMIBC) and 35% of MIBC recurrences. The mean BPR was 73% (49-100%). The mean metastatic recurrence rate was 9% (0-27%), while 5-yr OS rates ranged from 64% to 89%. With regard to radiation therapy, the median follow-up ranged from 12 to 60 mo, with a mean bladder recurrence rate of 15% (0-29%), including 24% of NMIBC, 43% of MIBC, and 33% of unspecified recurrences. The mean BPR was 74% (71-100%). The mean metastatic recurrence rate was 17% (0-22%), while the 4-yr OS rate was 79%. CONCLUSIONS: Our systematic review showed that only low-level evidence supports the effectiveness of BSSs in selected patients achieving cCR to initial systemic treatment for localized MIBC. These preliminary findings highlight the need for further prospective comparative research to demonstrate its efficacy. PATIENT SUMMARY: We reviewed studies evaluating bladder-sparing strategies in patients achieving complete clinical response to initial systemic treatment for localized muscle-invasive bladder cancer. Based on low-level evidence, we observed that selected patients could benefit from surveillance or radiation therapy in this setting, but prospective comparative research is requested to confirm their efficacy.

Asunto(s)

Neoplasias de la Vejiga Urinaria , Vejiga Urinaria , Humanos , Vejiga Urinaria/patología , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/patología , Cistectomía , Recurrencia

RESUMEN

BACKGROUND: The association between sarcopenia and response to neoadjuvant treatment remains unclear. This study investigates sarcopenia as a predictor of overall complete response (oCR) after Total Neoadjuvant Therapy (TNT) for advanced rectal cancer. METHOD: A prospective observational study was performed of patients with rectal cancer undergoing TNT at three South Australian hospitals between 2019 and 2022. Sarcopenia was diagnosed by pretreatment computed tomography measurement of psoas muscle cross-sectional area at the third lumbar vertebra level, normalised for patient height. The primary endpoint was oCR rate defined as the proportion of patients who achieved either clinical complete response (cCR) or pathological complete response. RESULTS: This study included 118 rectal cancer patients with an average age of 59.5 years, 83 (70.3%) of whom formed the non-sarcopenic group (NSG) and 35 (29.7%) the sarcopenic group (SG). The oCR rate was significantly higher in NSG compared with the SG (p < 0.001). cCR rate was significantly greater in NSG compared with the SG (p = 0.001). Multivariate analysis revealed sarcopenia (p = 0.029) and hypoalbuminemia (p = 0.040) were risk factors for cCR and sarcopenia was an independent risk factor for oCR (p = 0.020). CONCLUSION: Sarcopenia and hypoalbuminemia were negatively associated with tumour response following TNT in advanced rectal cancer patients.

Asunto(s)

Hipoalbuminemia , Neoplasias del Recto , Sarcopenia , Humanos , Persona de Mediana Edad , Sarcopenia/etiología , Sarcopenia/complicaciones , Terapia Neoadyuvante/efectos adversos , Hipoalbuminemia/complicaciones , Estudios Retrospectivos , Australia , Neoplasias del Recto/complicaciones , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Quimioradioterapia , Resultado del Tratamiento