[68Ga]Ga­PSMA­617 PET-based radiomics model to identify candidates for active surveillance amongst patients with GGG 1-2 prostate cancer at biopsy.

PURPOSE: To develop a radiomics-based model using [68Ga]Ga-PSMA PET/CT to predict postoperative adverse pathology (AP) in patients with biopsy Gleason Grade Group (GGG) 1-2 prostate cancer (PCa), assisting in the selection of patients for active surveillance (AS). METHODS: A total of 75 men with biopsy GGG 1-2 PCa who underwent radical prostatectomy (RP) were enrolled. The patients were randomly divided into a training group (70%) and a testing group (30%). Radiomics features of entire prostate were extracted from the [68Ga]Ga-PSMA PET scans and selected using the minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression model. Logistic regression analyses were conducted to construct the prediction models. Receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curve were employed to evaluate the diagnostic value, clinical utility, and predictive accuracy of the models, respectively. RESULTS: Among the 75 patients, 30 had AP confirmed by RP. The clinical model showed an area under the curve (AUC) of 0.821 (0.695-0.947) in the training set and 0.795 (0.603-0.987) in the testing set. The radiomics model achieved AUC values of 0.830 (0.720-0.941) in the training set and 0.829 (0.624-1.000) in the testing set. The combined model, which incorporated the Radiomics score (Radscore) and free prostate-specific antigen (FPSA)/total prostate-specific antigen (TPSA), demonstrated higher diagnostic efficacy than both the clinical and radiomics models, with AUC values of 0.875 (0.780-0.970) in the training set and 0.872 (0.678-1.000) in the testing set. DCA showed that the net benefits of the combined model and radiomics model exceeded those of the clinical model. CONCLUSION: The combined model shows potential in stratifying men with biopsy GGG 1-2 PCa based on the presence of AP at final pathology and outperforms models based solely on clinical or radiomics features. It may be expected to aid urologists in better selecting suitable patients for AS.

Effects of exercise during active surveillance for prostate cancer: A systematic review and meta-analysis.

PURPOSE: The efficacy of exercise in men with prostate cancer (PCa) on active surveillance (AS) remains unclear. In this meta-analysis, we aimed to examine the effects of exercise in PCa patients on AS. METHODS: A literature search was conducted in PubMed, EMBASE, and the Cochrane Library using search terms, including exercise, PCa, AS, and randomized controlled trials (RCTs). The means and standard deviations for peak oxygen consumption (VO2peak), prostate-specific antigen (PSA) levels, and quality of life (QoL) were extracted for the intervention and control groups. A random-effects model was used to summarize the effects of exercise. RESULTS: Of the 158 identified studies, six RCTs with 332 patients were included. The interventions included lifestyle modifications (aerobic exercise + diet) in three studies and different exercise modalities in three studies. The intervention duration was 2-12 months; three interventions were supervised and three were self-directed. The pooled weighted mean difference between exercise and usual care for VO2peak was 1.42 mL/kg/min (95% confidence interval [CI]: 0.30 to 2.54, P ≤ 0.001). A non-significant effect was observed for QoL (pooled standardized mean difference [SMD]: 0.24, 95% CI: - 0.03 to 0.51, P = 0.08) which became statistically significant and stronger after excluding one outlier study (P < 0.001). Exercise also had a positive effect on PSA levels (pooled SMD: - 0.43, 95% CI: - 0.87 to 0.01, P = 0.05). CONCLUSION: Exercise improves cardiorespiratory fitness and may improve QoL and PSA levels in men with PCa on AS. Further studies with larger sample sizes are warranted to obtain more reliable results.

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.

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.

Outcome of prelabor rupture of membranes before or at the limit of viability: systematic review and meta-analysis.

OBJECTIVE: Counseling of pregnancies complicated by pre- and periviable premature rupture of membranes to reach shared decision-making is challenging, and the current limited evidence hampers the robustness of the information provided. This study aimed to elucidate the rate of obstetrical and neonatal outcomes after expectant management for premature rupture of membranes occurring before or at the limit of viability. DATA SOURCES: Medline, Embase, CINAHL, and Web of Science databases were searched electronically up to September 2023. STUDY ELIGIBILITY CRITERIA: Our study included both prospective and retrospective studies of singleton pregnancies with premature rupture of membranes before and at the limit of viability (ie, occurring between 14 0/7 and 24 6/7 weeks of gestation). METHODS: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Moreover, our study used meta-analyses of proportions to combine data and reported pooled proportions. Given the clinical heterogeneity, a random-effects model was used to compute the pooled data analyses. This study was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42022368029). RESULTS: The pooled proportion of termination of pregnancy was 32.3%. After the exclusion of cases of termination of pregnancy, the rate of spontaneous miscarriage or fetal demise was 20.1%, whereas the rate of live birth was 65.9%. The mean gestational age at delivery among the live-born cases was 27.3 weeks, and the mean latency between premature rupture of membranes and delivery was 39.4 days. The pooled proportion of cesarean deliveries was 47.9% of the live-born cases. Oligohydramnios occurred in 47.1% of cases. Chorioamnionitis occurred in 33.4% of cases, endometritis in 7.0%, placental abruption in 9.2%, and postpartum hemorrhage in 5.3%. Hysterectomy was necessary in 1.2% of cases. Maternal sepsis occurred in 1.5% of cases, whereas no maternal death was reported in the included studies. When focusing on neonatal outcomes, the mean birthweight was 1022.8 g in live-born cases. The neonatal intensive care unit admission rate was 86.3%, respiratory distress syndrome was diagnosed in 66.5% of cases, pulmonary hypoplasia or dysplasia was diagnosed in 24.0% of cases, and persistent pulmonary hypertension was diagnosed in 40.9% of cases. Of the surviving neonates, the other neonatal complications included necrotizing enterocolitis in 11.1%, retinopathy of prematurity in 27.1%, and intraventricular hemorrhage in 17.5%. Neonatal sepsis occurred in 30.2% of cases, and the overall neonatal mortality was 23.9%. The long-term follow-up at 2 to 4 years was normal in 74.1% of the available cases. CONCLUSION: Premature rupture of membranes before or at the limit of viability was associated with a great burden of both obstetrical and neonatal complications, with an impaired long-term follow-up at 2 to 4 years in almost 30% of cases, representing a clinical challenge for both counseling and management. Our data are useful when initially approaching such patients to offer the most comprehensive possible scenario on short- and long-term outcomes of this condition and to help parents in shared decision-making. El resumen está disponible en Español al final del artículo.

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.

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.

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.

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.

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.