NCCN Guidelines® Insights: Prostate Cancer, Version 3.2024.

The NCCN Guidelines for Prostate Cancer include recommendations for staging and risk assessment after a prostate cancer diagnosis and for the care of patients with localized, regional, recurrent, and metastatic disease. These NCCN Guidelines Insights summarize the panel's discussions for the 2024 update to the guidelines with regard to initial risk stratification, initial management of very-low-risk disease, and the treatment of nonmetastatic recurrence.

Pragmatic clinical trials for localized prostate cancer: lessons learned and "three sins".

In "Explanatory and Pragmatic Attitudes in Therapeutic Trials", Schwatrz and Lelouch describe two approaches to the design of trials, "… the first "explanatory", the second "pragmatic". They explained "… the biologist may be interested to know whether the drugs differ in their effects … the explanatory approach". Biologically endpoints might determine whether it was better to give androgen deprivation therapy (ADT) before or after external beam radiation (EBRT) (i.e., does the sequence of treatments matter). Alternatively, if the arms focus on a clinical endpoint, this is considered … "the pragmatic approach". An example of a clinically relevant endpoint is overall survival (OS). A real-world example of this are the two randomized controlled trials (RCTs) evaluating the role of prophylactic whole pelvic radiotherapy (WPRT) conducted by the Radiation Therapy Oncology Group (RTOG). RTOG 9413 evaluated possible interactions between the sequence of drugs and volume irradiated, while RTOG/NRG 0924 focuses on OS. There appears to be a common pattern of "what not to do", or "design errors" made by a number of investigators, that I call the "three sins". I posit that the prospects for a well-designed pragmatic RCT are likely to be high if these "three sins" are avoided/minimized. The "three sins" alluded to are: 1. You can't prove something doesn't work by treating people who don't need the treatment. 2. You can't prove something does not work if the treatment is not done properly. 3. You can't prove something does not work with an underpowered study.

Primary cancer prevention for cancers with no known infectious etiology: Time for a new paradigm.

Vaccines developed for hepatitis B and human papilloma virus infections have been very successful in reducing the burden of cancer due to these infections. In the past decade, our understanding of the immunology of cancer has greatly improved and important progress has been made in the use of immunotherapy for several cancers. However, for the majority of cancers, an infectious etiology is either unknown or does not exist. Prostate cancer, for which no infectious etiology is known, is the most common cancer in men in the United States. Here we discuss the rationale for developing a preventive vaccine for prostate cancer, discuss a possible approach for further work in this area and a means of testing the effectiveness of a prostate cancer prevention vaccine in a clinical trial.

Disparities in the Delivery of Prostate Cancer Survivorship Care in the USA: A Claims-based Analysis of Urinary Adverse Events and Erectile Dysfunction Among Prostate Cancer Survivors.

Background and objective: Incidence rates for prostate cancer (PCa) diagnosis and mortality are higher for Black men. It is unknown whether similar disparities exist in survivorship care. We assessed the delivery and quality of survivorship care for Black men undergoing PCa therapy in terms of the burden of and treatment for urinary adverse events (UAEs) and erectile dysfunction (ED). Methods: We queried Optum Clinformatics data for all patients diagnosed with PCa from January 1, 2002 to December 31, 2017 and identified those who underwent primary PCa treatment. Index cohorts were identified in each year and followed longitudinally until 2017. Data for UAE diagnoses, UAE treatments, and ED treatments were analyzed in index cohorts. Cox proportional-hazards regression models were used to examine associations of race with UAE diagnosis, UAE treatment, and ED treatment. Key findings and limitations: We identified 146, 216 patients with a PCa diagnosis during the study period, of whom 55, 149 underwent primary PCa treatment. In the primary treatment group, 32.7% developed a UAE and 28.2% underwent UAE treatment. The most common UAEs were urinary incontinence (11%), ureteral obstruction/stricture (4.5%), bladder neck contracture (4.5%), and urethral stricture (3.7%). The most common UAE treatments were cystoscopy (13%), suprapubic tube placement (6%), and urethral dilation (5%). Overall, UAE diagnosis rates were higher for Black patients, who had significantly higher risk of urethral obstruction, rectourethral fistula, urinary incontinence, cystitis, urinary obstruction, and ureteral fistula. Overall, UAE treatment rates were lower for Black patients, who had significantly higher risk of fecal diversion and/or rectourethral fistula repair (adjusted hazard ratio [aHR] 1.71, 95% confidence interval [CI] 1.04-2.79). Regarding ED treatments, Black patients had higher risk of penile prosthesis placement (aHR 1.591, 95% CI 1.26-2.00) and intracavernosal injection (aHR 1.215, 95% CI 1.08-1.37). Conclusions and clinical implications: Despite a high UAE burden, treatment rates were low in a cohort with health insurance. Black patients had a higher UAE burden and lower UAE treatment rates. Multilevel interventions are needed to address this stark disparity. ED treatment rates were higher for Black patients. Patient summary: We reviewed data for patients treated for prostate cancer (PCa) and found that 32.7% were diagnosed with a urinary adverse event (UAE) following their PCa treatment. The overall treatment rate for these UAEs was 28.2%. Analysis by race showed that the UAE diagnosis rate was higher for Black patients, who were also more likely to receive treatment for erectile dysfunction.

Delayed definitive management of localized prostate cancer: what do we know?

Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202.

BACKGROUND: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM). OBJECTIVE: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202). DESIGN, SETTING, AND PARTICIPANTS: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using the Fine-Gray and Cox regression models, the relationship between ADT and mortality was evaluated. RESULTS AND LIMITATIONS: With a median follow-up of 19.6 yr, LTADT was associated with improved overall survival (OS) versus STADT (adjusted hazard ratio [HR] 0.88; p = 0.03) and prostate cancer survival (subdistribution HR [sHR] 0.70, p = 0.003). Comparing LTADT with STADT, prostate cancer mortality improved by 6.0% (15.6% [95% confidence interval 13.0-18.3%] vs 21.6% [18.6-24.7%]) at 15 yr, while CVM increased by 2.2% (14.9% [12.4-17.6%] vs 12.7% [10.4-15.3%]). In multivariable analyses, LTADT was not associated with increased CVM versus STADT (sHR 1.22 [0.93-1.59]; p = 0.15). An association between LTADT and MI death was detected (sHR 1.58 [1.00-2.50]; p = 0.05), particularly in patients with prevalent cardiovascular disease (CVD; sHR 2.54 [1.16-5.58]; p = 0.02). CONCLUSIONS: With 19.6 yr of follow-up, LTADT was not significantly associated with increased CVM in men with locally advanced prostate cancer. Patients may have increased MI mortality with LTADT, particularly those with baseline CVD. Overall, there remained a prostate cancer mortality benefit and no OS detriment with LTADT. PATIENT SUMMARY: In a long-term analysis of a large randomized prostate cancer trial, radiation with 28 mo of hormone therapy did not increase the risk of cardiovascular death significantly versus 4 mo of hormone therapy. Future studies are needed for patients with pre-existing heart disease, who may have an increased risk of myocardial infarction death with longer hormone use.

MRI-Linac-Based Radiotherapy-Promising or Hype?

This Viewpoint discusses the value of magnetic resonance imaging with linear accelerator (MRI-linac) technology, given the unmet needs in its development.