When less is more: Updates in active surveillance and watchful waiting in the management of prostate cancer.

BACKGROUND: Prostate cancer is the second most common cancer among men globally. A range of management options are available for prostate cancer, including surgery, radiation therapy, hormone therapy, chemotherapy, or surveillance. Conservative strategies include active surveillance and watchful waiting, which differ in their intent. OBJECTIVE: We provide a targeted instructive management algorithm for improving understanding of conservative strategies in prostate cancer. DISCUSSION: Active surveillance involves close monitoring with curative intent when there is evidence of disease progression. In contrast, watchful waiting is palliative in intent and focuses on delaying treatment until symptoms or complications develop. Conservative approaches have demonstrated similar long-term oncological outcomes to radical treatment, while reducing harm from overtreatment, and maintaining quality of life by avoiding potential side effects such as urinary incontinence and erectile dysfunction. The decision to employ a conservative approach is determined by both patient and disease factors. Conservative management strategies play a vital role in the management of prostate cancer.

Watch & wait - Post neoadjuvant imaging for rectal cancer.

Rectal cancer management has evolved over the past decade with the emergence of total neoadjuvant therapy (TNT). For select patients who achieve a clinical complete response following TNT, organ preservation by means of the watch-and-wait (WW) strategy is an increasingly adopted alternative that preserves rectal function and quality of life without compromising oncologic outcomes. Recently, published 5-year results from the OPRA trial demonstrated that organ preservation can be achieved in approximately half of patients managed with the WW strategy, with most local regrowth events occurring within two years. Considering the potential for local regrowth, the implementation of the WW strategy mandates rigorous clinical and radiographic surveillance. Magnetic resonance imaging (MRI) serves as the conventional imaging modality for local staging and surveillance of rectal cancer given its excellent soft-tissue resolution. This review will discuss the current evidence for the WW strategy and the role of restaging rectal MRI in determining patient eligibility for this strategy. Restaging rectal MRI acquisition parameters and treatment response assessment, including important factors to assess, pitfalls, and classification systems, will be discussed in the context of the WW strategy.

Active Surveillance in Non-Muscle Invasive Bladder Cancer, the Potential Role of Biomarkers: A Systematic Review.

Bladder cancer (BC) is the tenth most common cause of cancer worldwide and is the thirteenth leading cause of cancer mortality. The non-muscle invasive (NMI) variant represents 75% of cases and has a mortality rate of less than 1%; however, it has a high recurrence rate. The gold standard of management is transurethral resection in the case of new lesions. However, this is associated with significant morbidity and costs, so the reduction of these procedures would contribute to reducing complications, morbidity, and the burden to the health system associated with therapy. In this clinical scenario, strategies such as active surveillance have emerged that propose to manage low-risk BC with follow-up; however, due to the low evidence available, this is a strategy that is underutilized by clinicians. On the other hand, in the era of biomarkers, it is increasingly known how to use them as a tool in BC. Therefore, the aim of this review is to provide to clinical practitioners the evidence available to date on AS and the potential role of biomarkers in this therapeutic strategy in patients with low-grade/risk NMIBC. This is the first review linking use of biomarkers and active surveillance, including 29 articles.

Oncological Outcomes in Men With Favorable Intermediate Risk Prostate Cancer Enrolled in Active Surveillance.

BACKGROUND/AIM: To evaluate the long-term oncological outcomes in men with intermediate risk prostate cancer (PCa) enrolled in active surveillance (AS). PATIENTS AND METHODS: From April 2015 to December 2022, 30 men with Gleason score 3+4/ISUP Grade Group2 (GG2), greatest percentage of cancer (GPC) ≤50%, Gleason pattern 4 ≤10%, ≤3 positive biopsy cores were enrolled in AS. All patients underwent confirmatory transperineal saturation biopsy (SPBx: 20 cores) 12 months from diagnosis plus multiparametric magnetic resonance (mpMRI) evaluation. At the last follow-up, 68Ga prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) was added: lesions with PIRADS score ≥3 and/or standardized uptake value (SUVmax) >5 were submitted to four targeted cores. RESULTS: Three out of 30 (10%) men with GG2 PCa were reclassified at confirmatory biopsy. At the last follow-up (median 5.2 years), only 2 of 27 (7.4%) men were reclassified and 23/30 (76.6%) continued AS. CONCLUSION: Men with favorable GG2 PCa enrolled in AS have good long-term oncological results. The use of selective criteria (i.e., SPBx, mpMRI, PSMA PET/CT) reduces the risk of reclassification.

Cumulative cancer locations on prostate biopsy and active surveillance outcomes in the MRI era.

BACKGROUND: To validate the use of a cumulative cancer locations (CCLO) score, a measurement of tumor volume on biopsy, and to develop a novel magnetic resonance imaging (MRI)-informed CCLO (mCCLO) score to predict clinical outcomes on active surveillance (AS). METHODS: The CCLO score is a sum of uniquely involved sextants with prostate cancer on diagnostic + confirmatory biopsy. The mCCLO score incorporates MRI findings into the CCLO score. Participants included 1284 individuals enrolled on AS between 1994 and 2022, 343 of whom underwent prostate MRI. The primary outcome was grade reclassification (GR) to grade group ≥2 disease; the secondary outcome was receipt of definitive treatment. RESULTS: Increasing CCLO and mCCLO risk groups were associated with higher risk of GR and undergoing definitive treatment (both p < 0.001). On multivariable analysis, increasing mCCLO score was associated with higher risk of GR and receipt of definitive treatment (hazard ratios [HRs] per 1-unit increase: 1.26 [95% confidence interval [CI]: 1.12-1.41] and 1.21 [95% CI: 1.07-1.36], respectively). The model using mCCLO score to predict GR (c-index: 0.671; 95% CI: 0.621-0.721) performed at least as well as models using the number of cores positive for cancer (0.664 [0.613-0.715]; p = 0.7) and the maximum percentage of cancer in a core (0.641 [0.585-0.696]; p = 0.14). CONCLUSIONS: The CCLO score is a valid, objective metric to predict GR and receipt of treatment in a large AS cohort. The ability of the MRI-informed mCCLO to predict GR is on par with traditional metrics of tumor volume but is more descriptive and may benefit from greater reproducibility. The mCCLO score can be implemented as a shorthand, informative tool for counseling patients about whether to remain on AS.

Exploring the relation of active surveillance schedules and prostate cancer mortality.

BACKGROUND: Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long-term outcome, prostate cancer mortality. Nevertheless, this relation was never investigated in empirical data. Here, we use simulated data from a microsimulation model to fill this knowledge gap. METHODS: In this study, the established MIcrosimulation SCreening Analysis model was extended with functionality to simulate the AS procedures. The biopsy sensitivity in the model was calibrated on the Canary Prostate Cancer Active Surveillance Study (PASS) data, and four (tri-yearly, bi-yearly, PASS, and yearly) AS programs were simulated. The relation between detection delay and prostate cancer mortality was investigated by Cox models. RESULTS: The biopsy sensitivity of progression detection was found to be 50%. The Cox models show a positive relation between a longer detection delay and a higher risk of prostate cancer death. A 2-year delay resulted in a prostate cancer death risk of 2.46%-2.69% 5 years after progression detection and a 10-year risk of 5.75%-5.91%. A 4-year delay led to an approximately 8% greater 5-year risk and an approximately 25% greater 10-year risk. CONCLUSION: The detection delay is confirmed as a surrogate for prostate cancer mortality. A cut-off for a "safe" detection delay could not be identified.

Treatment Options for Distal Rectal Cancer in the Era of Organ Preservation.

OPINION STATEMENT: The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.

Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines.

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Whether the watch-and-wait strategy has application value for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy? A network meta-analysis.

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.

Which tumour factors preclude organ preservation in patients with rectal cancer?

BACKGROUND: cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes, extramural vascular invasion (EMVI) and mesorectal fascia threatening (MRF+) have been utilized as exclusion criteria in several studies on the watch-and-wait (w&w) strategy. Here, our aim was to validate these criteria through a post hoc analysis of two pooled prospective studies on w&w following routine radio(chemo)therapy. METHODS: A review of baseline magnetic resonance imaging was performed in a subgroup of 223 patients treated at a single institution. Of these, 17.9 % started w&w, 12.6 % achieved clinical complete response (cCR) and 9.0 % sustained cCR during median follow-up of 54 months. RESULTS: The multivariable logistic analysis showed that the proportion of circumferential bowel involvement and EMVI significantly influenced the chance of sustained cCR; odds ratios were 0.063 (95 % confidence interval [CI] 0.008-0.489, p = 0.008), and 0.109 (95 % CI 0.014-0.850, p = 0.034), respectively. Sustained cCR was observed in none of the 57 patients with 90 %-100 % circumferential bowel involvement and in only one of the 89 patients with EMVI. In contrast, cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes or MRF+ were not independently associated with sustained cCR. Among the subgroups of patients with these features but without (near-)circular tumour or EMVI+, sustained cCR was observed in 12 %-25 % of patients. CONCLUSION: Sustained cCR after routine preoperative radio(chemo)therapy is unlikely in patients with (near-)circular tumour or EMVI, whereas patients with cT3cdT4, cN2, mesorectal nodes > 8 mm, clinically positive lateral nodes and MRF+ should not be denied w&w.

The Brazilian national prospective active surveillance (AS) cohort of patients with low-risk prostate cancer in the public health system: vigiaSUS study protocol.

BACKGROUND: Prostate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system. METHODS: This is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/ml, will be enrolled. Archival prostate cancer tissue will be centrally reviewed. Patients enrolled in the study will follow the AS strategy, which involves PSA and physical examination every 6 months as well as multiparametric MRI (mpMRI) every two years and prostate biopsy at month 12 and then every two years. The primary objective is to evaluate the reclassification rate at 12 months, and secondary objectives include determining the treatment-free survival rate, metastasis-free survival, and specific and overall survival. Exploratory objectives include the evaluation of quality of life and anxiety, the impact of PTEN loss and the economic impact of AS on the Brazilian public health system. DISCUSSION: This is the first Brazilian prospective study of patients with low-risk prostate cancer under AS. To our knowledge, this is one of the largest AS study cohort with a majority of nonwhite patients. We believe that this study is an opportunity to better understand the outcomes of AS in populations underrepresented in studies. Based on these data, an AS national clinical guideline will be developed, which may have a beneficial impact on the quality of life of patients and on public health. TRIAL REGISTRATION: Clinicaltrials registration is NCT05343936.

Light and shadow of watch-and-wait strategy in rectal cancer: oncological result, clinical outcomes, and cost-effectiveness analysis.

BACKGROUND: The watch-and-wait (WW) strategy is a potential option for patients with rectal cancer who obtain a complete clinic response after neoadjuvant therapy. The aim of this study is to analyze the long-term oncological outcomes and perform a cost-effectiveness analysis in patients undergoing this strategy for rectal cancer. MATERIAL AND METHODS: The data of patients treated with the WW strategy were prospectively collected from January 2015 to January 2020. A control group was created, matched 1:1 from a pool of 480 patients undergoing total mesorectal excision. An independent company carried out the financial analysis. Clinical and oncological outcomes were analyzed in both groups. Outcome parameters included surgical and follow-up costs, quality-adjusted life years (QALYs), and the incremental cost per QALY gained or the incremental cost-effectiveness ratio (ICER). RESULTS: Forty patients were included in the WW group, with 40 patients in the surgical group. During a median follow-up period of 36 months, metastasis-free survival (MFS) and overall survival (OS) were similar in the two groups. In the WW group, nine (22%) local regrowths were detected in the first 2 years. The permanent stoma rate was slightly higher after salvage surgery in the WW group compared to the surgical group (48.5% vs 20%, p < 0.01). The cost-effectiveness analysis was slightly better for the WW group, especially for low rectal cancer compared to medium-high rectal cancer (ICER = - 108,642.1 vs ICER = - 42,423). CONCLUSIONS: The WW strategy in locally advanced rectal cancer offers similar oncological outcomes with respect to the surgical group and excellent results in quality of life and cost outcomes, especially for low rectal cancer. Nonetheless, the complex surgical field during salvage surgery can lead to a high permanent stoma rate; therefore, the careful selection of patients is mandatory.

Comparing Active Surveillance and Watchful Waiting With Radical Treatment Using Machine Learning Models Among Patients With Prostate Cancer.

PURPOSE: In 2021, 59.6% of low-risk patients with prostate cancer were under active surveillance (AS) as their first course of treatment. However, few studies have investigated AS and watchful waiting (WW) separately. The objectives of this study were to develop and validate a population-level machine learning model for distinguishing AS and WW in the conservative treatment group, and to investigate initial cancer management trends from 2004 to 2017 and the risk of chronic diseases among patients with prostate cancer with different treatment modalities. METHODS: In a cohort of 18,134 patients with prostate adenocarcinoma diagnosed between 2004 and 2017, 1,926 patients with available AS/WW information were analyzed using machine learning algorithms with 10-fold cross-validation. Models were evaluated using performance metrics and Brier score. Cox proportional hazard models were used to estimate hazard ratios for chronic disease risk. RESULTS: Logistic regression models achieved a test area under the receiver operating curve of 0.73, F-score of 0.79, accuracy of 0.71, and Brier score of 0.29, demonstrating good calibration, precision, and recall values. We noted a sharp increase in AS use between 2004 and 2016 among patients with low-risk prostate cancer and a moderate increase among intermediate-risk patients between 2008 and 2017. Compared with the AS group, radical treatment was associated with a lower risk of prostate cancer-specific mortality but higher risks of Alzheimer disease, anemia, glaucoma, hyperlipidemia, and hypertension. CONCLUSION: A machine learning approach accurately distinguished AS and WW groups in conservative treatment in this decision analytical model study. Our results provide insight into the necessity to separate AS and WW in population-based studies.

Active surveillance should be considered for select men with Grade Group 2 prostate cancer.

BACKGROUND: Treatment decisions for localized prostate cancer must balance patient preferences, oncologic risk, and preservation of sexual, urinary and bowel function. While Active Surveillance (AS) is the recommended option for men with Grade Group 1 (Gleason Score 3 + 3 = 6) prostate cancer without other intermediate-risk features, men with Grade Group 2 (Gleason Score 3 + 4 = 7) are typically recommended active treatment. For select patients, AS can be a possible initial management strategy for men with Grade Group 2. Herein, we review current urology guidelines and the urologic literature regarding recommendations and evidence for AS for this patient group. MAIN BODY: AS benefits men with prostate cancer by maintaining their current quality of life and avoiding treatment side effects. AS protocols with close follow up always allow for an option to change course and pursue curative treatment. All the major guideline organizations now include Grade Group 2 disease with slightly differing definitions of eligibility based on risk using prostate-specific antigen (PSA) level, Gleason score, clinical stage, and other factors. Selected men with Grade Group 2 on AS have similar rates of deferred treatment and metastasis to men with Grade Group 1 on AS. There is a growing body of evidence from randomized controlled trials, large observational (prospective and retrospective) cohorts that confirm the oncologic safety of AS for these men. While some men will inevitably conclude AS at some point due to clinical reclassification with biopsy or imaging, some men may be able to stay on AS until transition to watchful waiting (WW). Magnetic resonance imaging is an important tool to confirm AS eligibility, to monitor progression and guide prostate biopsy. CONCLUSION: AS is a viable initial management option for well-informed and select men with Grade Group 2 prostate cancer, low volume of pattern 4, and no other adverse clinicopathologic findings following a well-defined monitoring protocol. In the modern era of AS, urologists have tools at their disposal to better stage patients at initial diagnosis, risk stratify patients, and gain information on the biologic potential of a patient's prostate cancer.

Baseline prostate health index risk category and risk category changes during active surveillance predict grade reclassification.

BACKGROUND: It is not known whether baseline prostate health index (PHI) at the initiation of active surveillance (AS) or repeated PHI testing during AS is of clinical value after confirmatory biopsy in AS men followed with multiparametric magnetic resonance imaging (mpMRI). METHODS: We identified 382 AS patients with no greater than Grade Group 1 (GG1) prostate cancer on diagnostic and confirmatory biopsy, at least one mpMRI and PHI test, of which 241 had at least 2 PHI tests. Grade reclassification (GR) was defined as ≥GG2 on surveillance biopsy. PHI risk categories 1 to 4 were as defined by the manufacturer. Associations between baseline PHI risk category or baseline PSA density (PSAD), change in PHI risk categories over time or PSAD changes over time and GR were evaluated with multivariable Cox proportional hazard regression models adjusted for age, Prostate Imaging-Reporting and Data System score and number of positive cores. RESULTS: Men with baseline PHI scores in the highest risk categories had lower rates of GR-free survival (log-rank P < 0.001), as did those who increased in PHI risk category or remained in a high PHI risk category during surveillance (log-rank P = 0.032). On multivariable regression, baseline PHI risk category was a predictor of GR (risk category 4 [vs. 1] hazard ratio [HR] 2.74, 95% confidence interval [CI] 1.32-5.66, P = 0.002, model C-index 0.764, Akaike Information Criterion [AIC] 797), as were PHI risk category changes over time (risk category 4 [vs. 1] HR 4.20, 95% CI 1.76-10.05, P = 0.002, C-index 0.759, AIC 489). Separate models with baseline PSAD and PSAD changes over time yielded C-indices of 0.709 (AIC 809) and 0.733 (AIC 495) respectively. CONCLUSIONS: Baseline PHI risk category and PHI changes over time were both independent predictors of GR after confirmatory biopsy, but the added benefit over PSAD seemed modest. However, baseline PHI and PHI risk category changes provided clinically useful risk stratification for time to GR, so further evaluation of PHI's ability to help reduce the frequency of mpMRI and/or surveillance biopsies with more PHI data points over time may be warranted.

The Crying Need for a Better Response Assessment in Rectal Cancer.

OPINION STATEMENT: Since total neoadjuvant treatment achieves almost 30% pathologic complete response, organ preservation has been increasingly debated for good responders after neoadjuvant treatment for patients diagnosed with rectal cancer. Two organ preservation strategies are available: a watch and wait strategy and a local excision strategy including patients with a near clinical complete response. A major issue is the selection of patients according to the initial tumor staging or the response assessment. Despite modern imaging improvement, identifying complete response remains challenging. A better selection could be possible by radiomics analyses, exploiting numerous image features to feed data characterization algorithms. The subsequent step is to include baseline and/or pre-therapeutic MRI, PET-CT, and CT radiomics added to the patients' clinicopathological data, inside machine learning (ML) prediction models, with predictive or prognostic purposes. These models could be further improved by the addition of new biomarkers such as circulating tumor biomarkers, molecular profiling, or pathological immune biomarkers.

Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial.

Importance: Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically. Objective: To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma. Design, Setting, and Participants: Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021. Interventions: Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires. Main Outcomes and Measures: The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications. Results: Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed. Conclusion and relevance: Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02249572.

Is Nonoperative Management of Rectal Cancer Feasible?

During the past decade, the treatment of locally advanced rectal cancer (LARC) has become more complex. Total neoadjuvant treatment (TNT) has increased the rates of both clinical and pathologic complete response, resulting in improved long-term oncological outcomes. The feasibility to implement nonoperative management (NOM) depends on solving current challenges such as how to correctly identify the best candidates for a NOM without compromising oncologic safety. NOM should be part of the treatment discussion of LARC, considering increasing rates of clinical complete response, potential quality of life gains, avoidance of surgical morbidity, and patient preferences.

Watch and Wait for rectal cancer in inflammatory bowel disease.

Colorectal cancer is currently the third most frequently diagnosed type of cancer and the second cause of cancer death in the western world. Inflammatory bowel disease patients are 2-6 times more likely to develop CRC than the general population. Patients with CRC arising through Inflammatory Bowel Disease have an indication for surgery. However, in patients without Inflammatory Bowel Disease, the use of organ (rectum) preservation strategies after neoadjuvant treatment is on the rise, which means that patients are able to keep the organ without the need for complete excision, either by treatment with radiotherapy and chemotherapy, or in combination with endoscopic or surgical techniques that allow local excision without the need for resection of the entire organ. The patient management approach known as the Watch and Wait programme was first introduced in 2004 by a team from São Paulo, Brazil. This approach suggested that patients who had an excellent or complete clinical response after neoadjuvant treatment could defer surgery and instead undergo Watch and Wait. This organ preservation technique became popular because it allowed patients to avoid the complications associated with major surgery while achieving similar oncological outcomes to those who underwent both neoadjuvant therapy and radical surgery. Following completion of neoadjuvant treatment, a decision to defer surgery is made based on whether a clinical Complete Response can be achieved, which means there is no evidence of tumour in clinical and radiological examination. The International Watch and Wait Database has published long-term oncological outcomes for patients treated with this strategy, and more patients are showing interest in this treatment option. However, it is important to note that up to 1/3 of patients selected for Watch and Wait may eventually require surgery for local regrowth (also known as 'deferred definitive surgery') at any time during follow-up after an initial 'apparent' clinical Complete Response. Compliance with a strict surveillance protocol ensures early detection of regrowth, which is usually amenable to R0 surgery and provides excellent long-term local disease control. Nonetheless, it is crucial to assess the perioperative consequences of having surgery for regrowth later and whether there are any negative effects from deferring surgery. Currently, the Watch and Wait strategy is recommended in the NCCN guidelines for clinical complete responders and only in specialised multidisciplinary centres.There is no case in the literature that portrays the use of the Watch and Wait programme for patients with inflammatory bowel disease and rectal cancer.The authors intend to present a case that demonstrates the difficulties in the assessment of patients with inflammatory bowel disease, the risks of using radiotherapy in this patients and the challenges of surveillance for patients with colorectal cancer and inflammatory bowel disease.

Retrospective analysis of the uptake of active surveillance for low-risk prostate cancer in Zurich, Switzerland.

OBJECTIVES: Active surveillance for low-risk prostate cancer closely monitors patients conservatively instead of the pursuit of active treatment to reduce overtreatment of insignificant disease. Since 2009, active surveillance has been recommended as the primary management option in the European Association of Urology guidelines for low-risk disease. The present study aimed to investigate the use and uptake of active surveillance over 10 years in our certified prostate cancer centre (University Hospital of Zurich) compared with those derived from the cancer registry of the canton of Zurich, Switzerland. MATERIALS AND METHODS: We retrospectively identified all men diagnosed with low-risk prostate cancer at our institution and from the cancer registry of the canton of Zurich from 2009 to 2018. The primary treatment of each patient was recorded. Descriptive statistics were used to analyze the use of different treatments in our centre. The results were compared with those derived from the cancer registry. RESULTS: A total of 3393 men with low-risk prostate cancer were included in this study (University Hospital of Zurich: n = 262; cancer registry: n = 3131). In the University Hospital of Zurich and cancer registry cohorts, 146 (55.7%) and 502 (16%) men underwent active surveillance, respectively. The proportions of local treatment [115 (43.9%) vs 2220 (71%)] and androgen deprivation therapy [0 (0%) vs 43 (1.4%)] were distinctly lower in the University Hospital of Zurich cohort than in the cancer registry cohort. The uptake of active surveillance over the years was high in the University Hospital of Zurich cohort (35.4% in 2009 and 88.2% in 2018) but only marginal in the cancer registry cohort (12.2% in 2009 and 16.2% in 2018). CONCLUSION: Despite clear guideline recommendations, active surveillance for low-risk prostate cancer is still widely underused. Our analysis showed that access to a certified interdisciplinary tumour board significantly increases the use of active surveillance.